subject:(phospholipase D)

University of Alberta

1. Capatos, Dora. Role of Lipins in Regulating Phospholipase D Signalling.

Degree: MS, Department of Biochemistry, 2013, University of Alberta

URL: https://era.library.ualberta.ca/files/00000130x

► A potential therapeutic target in cancer is phospholipase D (PLD), which converts phosphatidylcholine into phosphatidic acid, a lipid second messenger in cell signalling. The lipid… (more)

Subjects/Keywords: Phospholipase D Signalling; Lipin; Phospholipase D

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APA (6^th Edition):

Capatos, D. (2013). Role of Lipins in Regulating Phospholipase D Signalling. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/00000130x

Chicago Manual of Style (16^th Edition):

Capatos, Dora. “Role of Lipins in Regulating Phospholipase D Signalling.” 2013. Masters Thesis, University of Alberta. Accessed January 20, 2021. https://era.library.ualberta.ca/files/00000130x.

MLA Handbook (7^th Edition):

Capatos, Dora. “Role of Lipins in Regulating Phospholipase D Signalling.” 2013. Web. 20 Jan 2021.

Vancouver:

Capatos D. Role of Lipins in Regulating Phospholipase D Signalling. [Internet] [Masters thesis]. University of Alberta; 2013. [cited 2021 Jan 20]. Available from: https://era.library.ualberta.ca/files/00000130x.

Council of Science Editors:

Capatos D. Role of Lipins in Regulating Phospholipase D Signalling. [Masters Thesis]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/00000130x

2. Uesugi, Yoshiko. Studies on the catalytic reaction of Streptomyces phospholipase D : Phospholipase Dの反応性に関する研究; Phospholipase D ノハンノウセイニカンスルケンキュウ.

Degree: Nara Institute of Science and Technology / 奈良先端科学技術大学院大学

URL: http://hdl.handle.net/10061/4001

Subjects/Keywords: Phospholipase D

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APA (6^th Edition):

Uesugi, Y. (n.d.). Studies on the catalytic reaction of Streptomyces phospholipase D : Phospholipase Dの反応性に関する研究; Phospholipase D ノハンノウセイニカンスルケンキュウ. (Thesis). Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Retrieved from http://hdl.handle.net/10061/4001

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Uesugi, Yoshiko. “Studies on the catalytic reaction of Streptomyces phospholipase D : Phospholipase Dの反応性に関する研究; Phospholipase D ノハンノウセイニカンスルケンキュウ.” Thesis, Nara Institute of Science and Technology / 奈良先端科学技術大学院大学. Accessed January 20, 2021. http://hdl.handle.net/10061/4001.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Uesugi, Yoshiko. “Studies on the catalytic reaction of Streptomyces phospholipase D : Phospholipase Dの反応性に関する研究; Phospholipase D ノハンノウセイニカンスルケンキュウ.” Web. 20 Jan 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Uesugi Y. Studies on the catalytic reaction of Streptomyces phospholipase D : Phospholipase Dの反応性に関する研究; Phospholipase D ノハンノウセイニカンスルケンキュウ. [Internet] [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10061/4001.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Uesugi Y. Studies on the catalytic reaction of Streptomyces phospholipase D : Phospholipase Dの反応性に関する研究; Phospholipase D ノハンノウセイニカンスルケンキュウ. [Thesis]. Nara Institute of Science and Technology / 奈良先端科学技術大学院大学; Available from: http://hdl.handle.net/10061/4001

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Vanderbilt University

3. Lavieri, Robert Raymond. Synthesis, development and biochemical characterization of small molecule, isoform-selective phospholipase D inhibitors and photoactivatable probes.

Degree: PhD, Pharmacology, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/14434

► Phospholipase D (PLD) catalyzes the production of the lipid second messenger phosphatidic acid (PtdOH). PLD expression and/or enzymatic activity are both elevated in a variety… (more)

▼ Phospholipase D (PLD) catalyzes the production of the lipid second messenger phosphatidic acid (PtdOH). PLD expression and/or enzymatic activity are both elevated in a variety of human cancers. Inhibition of PLD enzymatic activity, via genetic or biochemical methods, leads to decreased cancer cell invasion and decreased cancer cell survival. The aforementioned evidence provided the impetus for a medicinal chemistry project focused on the development of isoform-selective PLD inhibitors. A group from Novartis published a report in 2007 disclosing halopemide as a hit from a high throughput screen for PLD inhibitors. While the iterative analog synthesis campaign described in this dissertation began with halopemide a broad chemical space was explored through the synthesis of several hundred compounds. This effort yielded the most potent, isoform-selective PLD inhibitors ever described. Halopemide inhibits both PLD isoforms relatively equally; VU0359595 inhibits PLD1 1,700 times more potently than PLD2, and VU0364739 inhibits PLD2 75 times more potently than PLD1. An aryl(trifluoromethyl)diazirine containing photoprobe based on the structure of VU0359595 was prepared and was found to inhibit a truncated form of PLD missing the first 311 amino acids, PLD1c.d311. Subsequently, the ability of the probe to covalently modify PLD1c.cd311 was verified. Tandem mass spectrometry experiments to identify the covalently labeled peptide(s) and potentially amino acid(s) are ongoing. In addition to the chemical synthesis of PLD inhibitors and photolabeling experiments some molecular mechanism of action studies were conducted. The VU series of PLD inhibitors block catalysis of both lipososomal and monomeric substrates. Unfortunately, Michealis-Menten kinetics experiments were unable to be performed, because the truncated form of PLD2, PLD2.d308, displays substrate inhibition kinetics in a monomeric substrate containing enzyme activity assay. This research has provided chemical probes that are facilitating the study, both in vitro and in vivo, of how the two mammalian isoforms of PLD affect diverse physiological and pathological processes. Advisors/Committee Members: Lawrence J. Marnett (committee member), H. Alex Brown (committee member), Craig W. Lindsley (committee member), David Cortez (committee member), Tina M. Iverson (Committee Chair).

Subjects/Keywords: inhibitors; photoprobe; Phospholipase D; halopemide

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APA (6^th Edition):

Lavieri, R. R. (2014). Synthesis, development and biochemical characterization of small molecule, isoform-selective phospholipase D inhibitors and photoactivatable probes. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14434

Chicago Manual of Style (16^th Edition):

Lavieri, Robert Raymond. “Synthesis, development and biochemical characterization of small molecule, isoform-selective phospholipase D inhibitors and photoactivatable probes.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/14434.

MLA Handbook (7^th Edition):

Lavieri, Robert Raymond. “Synthesis, development and biochemical characterization of small molecule, isoform-selective phospholipase D inhibitors and photoactivatable probes.” 2014. Web. 20 Jan 2021.

Vancouver:

Lavieri RR. Synthesis, development and biochemical characterization of small molecule, isoform-selective phospholipase D inhibitors and photoactivatable probes. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/14434.

Council of Science Editors:

Lavieri RR. Synthesis, development and biochemical characterization of small molecule, isoform-selective phospholipase D inhibitors and photoactivatable probes. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/14434

University of Guelph

4. Brandt, Robert. Effect of Hexanal Formulations on the Postharvest Quality and Gene Expression of Strawberry (Fragaria x ananassa Duch.).

Degree: MS, Department of Plant Agriculture, 2019, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/14761

► Food waste is a major concern with the growing world population. Research was conducted using hexanal based formulations to improve the shelf-life of strawberry. Pre-harvest… (more)

Subjects/Keywords: Phospholipase D; Hexanal; Postharvest; Strawberry

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APA (6^th Edition):

Brandt, R. (2019). Effect of Hexanal Formulations on the Postharvest Quality and Gene Expression of Strawberry (Fragaria x ananassa Duch.). (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/14761

Chicago Manual of Style (16^th Edition):

Brandt, Robert. “Effect of Hexanal Formulations on the Postharvest Quality and Gene Expression of Strawberry (Fragaria x ananassa Duch.).” 2019. Masters Thesis, University of Guelph. Accessed January 20, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/14761.

MLA Handbook (7^th Edition):

Brandt, Robert. “Effect of Hexanal Formulations on the Postharvest Quality and Gene Expression of Strawberry (Fragaria x ananassa Duch.).” 2019. Web. 20 Jan 2021.

Vancouver:

Brandt R. Effect of Hexanal Formulations on the Postharvest Quality and Gene Expression of Strawberry (Fragaria x ananassa Duch.). [Internet] [Masters thesis]. University of Guelph; 2019. [cited 2021 Jan 20]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/14761.

Council of Science Editors:

Brandt R. Effect of Hexanal Formulations on the Postharvest Quality and Gene Expression of Strawberry (Fragaria x ananassa Duch.). [Masters Thesis]. University of Guelph; 2019. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/14761

Vanderbilt University

5. Spencer, Cierra Tamese. Biochemical characterization of a Pseudomonas aeruginosa phospholipase D.

Degree: PhD, Pharmacology, 2015, Vanderbilt University

URL: http://hdl.handle.net/1803/10428

► Phospholipase D (PLD) is a ubiquitous enzyme found in prokaryotic and eukaryotic organisms that generates phosphatidic acid. A number of human bacterial pathogens produce PLD… (more)

Subjects/Keywords: phospholipase D; enzymology; bacterial virulence

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APA (6^th Edition):

Spencer, C. T. (2015). Biochemical characterization of a Pseudomonas aeruginosa phospholipase D. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10428

Chicago Manual of Style (16^th Edition):

Spencer, Cierra Tamese. “Biochemical characterization of a Pseudomonas aeruginosa phospholipase D.” 2015. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/10428.

MLA Handbook (7^th Edition):

Spencer, Cierra Tamese. “Biochemical characterization of a Pseudomonas aeruginosa phospholipase D.” 2015. Web. 20 Jan 2021.

Vancouver:

Spencer CT. Biochemical characterization of a Pseudomonas aeruginosa phospholipase D. [Internet] [Doctoral dissertation]. Vanderbilt University; 2015. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/10428.

Council of Science Editors:

Spencer CT. Biochemical characterization of a Pseudomonas aeruginosa phospholipase D. [Doctoral Dissertation]. Vanderbilt University; 2015. Available from: http://hdl.handle.net/1803/10428

6. Jaafar, Rami. Régulation des la voie mTOR par la phospholipase D dans le muscle squelettique : implication dans le contrôle de la différenciation myogénique et de la taille des myocytes : Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size.

Degree: Docteur es, Biochimie, 2011, INSA Lyon

URL: http://www.theses.fr/2011ISAL0009

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La phospholipase D (PLD) hydrolyse la phosphatidylcholine des membranes cellulaires, libérant le messager acide phosphatidique. La capacité de la PLD à influer sur la voie… (more)

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La phospholipase D (PLD) hydrolyse la phosphatidylcholine des membranes cellulaires, libérant le messager acide phosphatidique. La capacité de la PLD à influer sur la voie de signalisation de mTOR, acteur central dans le contrôle du tissu musculaire, nous a incités à étudier son rôle dans ce tissu. Mes travaux de thèse ont pour but d'étudier les mécanismes par lesquels la PLD intervient dans la différenciation myogénique et dans la régulation de la masse musculaire. Dans un premier temps, nous avons montré que le contrôle de la différenciation des myoblastes L6 par la PLD met en jeu l'activation des deux complexes de mTOR (mTORC1 et mTORC2). mTORC2 active la différenciation, probablement via son effecteur PKCalpha, alors que mTORC1 la réprime via son effecteur S6K1, en induisant la phosphorylation de rictor, un composant de mTORC2, et l'inhibition de ce complexe. Nous avons par ailleurs montré que l'extinction de PLD par interférence de I'ARN induit l'atrophie de myotubes L6 en culture, ainsi qu'une baisse de la phosphorylation de S6K1 et 4E-BP1, effecteurs de mTORC1. Inversement, la surexpression de PLD à l'aide de vecteurs adénoviraux induit une hypertrophie des myotubes, associée à une activation de la voie mTORC1, et de Akt, effecteur de mTORC2. De plus, la surexpression de PLD atténue l'atrophie induite par la dexaméthasone. Ces résultats mettent en évidence un rôle hypertrophique et anti-atrophique de la PLD, qui pourrait s'exercer par stimulation de la voie mTOR. Nos résultats suggèrent que la PLD est susceptible de jouer un rôle clé dans le muscle squelettique, en agissant tant au niveau de la régénération du tissu qu'au niveau de la régulation de sa masse.

Phospholipase D (PLD) hydrolyzes phosphatidylcholine of cell membranes, releasing the lipid messenger phosphatidic acid. The ability of PLD to affect mTOR signaling pathway, a central actor in the control of muscle tissue, prompted us to study its role in this tissue. My thesis aims at investigating how PLD is involved in myogenic differentiation, and how it regulates muscle mass. We first showed that the mechanism by which PLD controls differentiation of L6 myoblasts involves the activation of the two mTOR complexes (mTORC1 and mTORC2). mTORC2 activates differentiation, probably via its effector PKCalpha, whereas mTORC1 represses differentiation via its effector S6K1, by inducing the phosphorylation of Rictor, a component of mTORC2, and the inhibition of this complex. Besides, we showed that extinction of PLD by RNA interference induces the atrophy of L6 myotubes, and decreases the phosphorylation of the mTORC1 effectors S6K1 and 4E-BP1. Conversely, overexpression of PLD using adenoviral vectors induces the hypertrophy of myotubes and the activation of both mTORC1 pathway and the mTORC2 effector Akt. Furthermore, PLD overexpression attenuates atrophy induced by dexamethasone. These results highlight a hypertrophic and anti-atrophic role of PLD, which could be achieved through stimulation of the mTOR pathway. Our results suggest that PLD is likely to…

Advisors/Committee Members: Nemoz, Georges (thesis director).

Subjects/Keywords: Biosciences; Biochimie; Phospholipase D; Différenciation myogénique; Biosciences; Biochemistry; Phospholipase D; Myogenic differenciation; 572.507 2

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APA (6^th Edition):

Jaafar, R. (2011). Régulation des la voie mTOR par la phospholipase D dans le muscle squelettique : implication dans le contrôle de la différenciation myogénique et de la taille des myocytes : Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size. (Doctoral Dissertation). INSA Lyon. Retrieved from http://www.theses.fr/2011ISAL0009

Chicago Manual of Style (16^th Edition):

Jaafar, Rami. “Régulation des la voie mTOR par la phospholipase D dans le muscle squelettique : implication dans le contrôle de la différenciation myogénique et de la taille des myocytes : Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size.” 2011. Doctoral Dissertation, INSA Lyon. Accessed January 20, 2021. http://www.theses.fr/2011ISAL0009.

MLA Handbook (7^th Edition):

Jaafar, Rami. “Régulation des la voie mTOR par la phospholipase D dans le muscle squelettique : implication dans le contrôle de la différenciation myogénique et de la taille des myocytes : Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size.” 2011. Web. 20 Jan 2021.

Vancouver:

Jaafar R. Régulation des la voie mTOR par la phospholipase D dans le muscle squelettique : implication dans le contrôle de la différenciation myogénique et de la taille des myocytes : Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size. [Internet] [Doctoral dissertation]. INSA Lyon; 2011. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2011ISAL0009.

Council of Science Editors:

Jaafar R. Régulation des la voie mTOR par la phospholipase D dans le muscle squelettique : implication dans le contrôle de la différenciation myogénique et de la taille des myocytes : Regulation of mammalian target of rapamycin (mTOR) by phospholipase D : role in the control of myogenic differentiation and myocytes size. [Doctoral Dissertation]. INSA Lyon; 2011. Available from: http://www.theses.fr/2011ISAL0009

Université de Lorraine

7. Gkikopoulou, Effrosyni. Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1 : Une cible pharmacologique nouvelle pour la chimiothérapie ? : Repression cobalamin-dependent signaling pathways of MDR-1 gene : A new pharmacological target for chemotherapy?.

Degree: Docteur es, Sciences de la vie et de la santé, 2012, Université de Lorraine

URL: http://www.theses.fr/2012LORR0305

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La résistance aux agents anticancéreux souvent observée en chimiothérapie s'accompagne d'une augmentation de l'expression des gènes tels que MDR-1, gérée par des réactions de méthylation… (more)

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La résistance aux agents anticancéreux souvent observée en chimiothérapie s'accompagne d'une augmentation de l'expression des gènes tels que MDR-1, gérée par des réactions de méthylation cellulaire. La physiologie des réactions de méthylation régulant l'expression de MDR-1 est insuffisamment connue. La méthionine synthase est l'enzyme clé du cycle métabolique de la méthionine et possède comme cofacteur la cobalamine (vitamine B12), suggérant un rôle crucial du couple cobalamine / méthionine synthase dans la survenue de la chimio-résistance par l'intermédiaire de la méthylation. Nous avions trouvé que l'ajout de cobalamine à des cellules d'adénocarcinome hépatique conduisait à une répression du gène MDR-1 qui ne passe pas par la méthylation du promoteur. Notre objectif est d'explorer et d'étudier les voies métaboliques situées entre le cycle de la méthionine et l'expression du gène MDR-1. Des techniques chromatographiques, électrophorétiques, de culture cellulaire, de pharmacotoxicologie et d'expression génique sont utilisées sur la lignée HepG2. La répression cobalamine-dépendante du gène MDR-1 est associée à une activation de la PLD, une diminution du facteur de signalisation Akt ainsi qu'à une inhibition de Cox2. Le ciblage pharmacologique de ces voies semble potentialiser l'effet d'agents utilisés en chimiothérapie. Cette étude devrait permettre de mieux comprendre des mécanismes de chimiorésistance, de déterminer des paramètres d'optimisation de l'utilisation de ces anticancéreux en relation avec l'expression de MDR-1 elle même en relation avec le statut vitaminique B et peut être d'orienter la recherche en chimiothérapie vers de nouvelles voies thérapeutiques

A key factor of chemioresistance is an increased expression of MDR-1 gene, partly controlled by cellular methylation reactions. Until now, the physiology of these reactions is not clearly known. The main intracellular metabolic pathway, generating methyl donors, is the methionine cycle, the activity of which is strongly depending on B-group vitamins (B12, B9). Thus, MDR-1 gene expression may be controlled by the activity of the methionine cycle and consequently presence of these vitamins. The aim of this study is to determine if, and to elucidate how, the methionine cycle influences the MDR-1 gene expression. Chromatography, pharmacotoxicology, cell culture techniques, gene and protein expression studies have been used on the human hepatocarcinoma cell line HepG2. We showed that cobalamin-induced MDR-1 gene repression was associated with phospholipase D activation, Akt phosphorylation, and Cox-2 co-repression in a complex and intricated manner. We may suggest that targeting these pathways could potentiate chimotherapy. This work shoiuld allow 1) a better understanding of mechanisms explaining why some anticancer agents may become inactive, 2) to optimize utilisation of these agents in relationship with MDR-1 gene expression and the B vitamin status, 3) to evaluate impacts of nutritionnal factors (cobalamine) in MDR-1 gene expression and 4) probably…

Advisors/Committee Members: Merten, Marc (thesis director).

Subjects/Keywords: Multi-drogue résistance; Vitamine B12; Phospholipase D; Akt; Cyclooxygénase 2; Multidrug resistance; Vitamin B12; Phospholipase D; Akt; Cyclooxygenase 2; 572.58; 615.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gkikopoulou, E. (2012). Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1 : Une cible pharmacologique nouvelle pour la chimiothérapie ? : Repression cobalamin-dependent signaling pathways of MDR-1 gene : A new pharmacological target for chemotherapy?. (Doctoral Dissertation). Université de Lorraine. Retrieved from http://www.theses.fr/2012LORR0305

Chicago Manual of Style (16^th Edition):

Gkikopoulou, Effrosyni. “Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1 : Une cible pharmacologique nouvelle pour la chimiothérapie ? : Repression cobalamin-dependent signaling pathways of MDR-1 gene : A new pharmacological target for chemotherapy?.” 2012. Doctoral Dissertation, Université de Lorraine. Accessed January 20, 2021. http://www.theses.fr/2012LORR0305.

MLA Handbook (7^th Edition):

Gkikopoulou, Effrosyni. “Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1 : Une cible pharmacologique nouvelle pour la chimiothérapie ? : Repression cobalamin-dependent signaling pathways of MDR-1 gene : A new pharmacological target for chemotherapy?.” 2012. Web. 20 Jan 2021.

Vancouver:

Gkikopoulou E. Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1 : Une cible pharmacologique nouvelle pour la chimiothérapie ? : Repression cobalamin-dependent signaling pathways of MDR-1 gene : A new pharmacological target for chemotherapy?. [Internet] [Doctoral dissertation]. Université de Lorraine; 2012. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2012LORR0305.

Council of Science Editors:

Gkikopoulou E. Voies de signalisation cobalamine-dépendantes de l'expression du gène MDR-1 : Une cible pharmacologique nouvelle pour la chimiothérapie ? : Repression cobalamin-dependent signaling pathways of MDR-1 gene : A new pharmacological target for chemotherapy?. [Doctoral Dissertation]. Université de Lorraine; 2012. Available from: http://www.theses.fr/2012LORR0305

8. Abdallah, Dina. Fonctions de la phospholipase D et des récepteurs de la prostaglandine PGE2 durant la maturation des ostéoblastes, le processus de la minéralisation physiologique et la calcification cardiovasculaire : Functions of phospholipase D and PGE2 prostaglandin receptors during the maturation of osteoblasts, physiological mineralization and cardiovascular calcification process.

Degree: Docteur es, Biochimie, 2014, Université Claude Bernard – Lyon I

URL: http://www.theses.fr/2014LYO10152

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Le métabolisme lipidique affecte la maturation et la différenciation des cellules osseuses. L'objectif de ma thèse est d'approfondir deux aspects du métabolisme lipidique mal connus,… (more)

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Le métabolisme lipidique affecte la maturation et la différenciation des cellules osseuses. L'objectif de ma thèse est d'approfondir deux aspects du métabolisme lipidique mal connus, soit les actions de la phospholipase D (PLD) et celles des récepteurs de prostaglandine PGE2 pendant la différenciation des cellules. Une lignée humaine, les Saos-2 et les ostéoblastes primaires issus de calvaria de souriceaux ont servi de modèles cellulaires de la minéralisation physiologique. La culture d'aorte ex vivo sous des conditions d'hyperphosphatémie a été utilisée pour reproduire la calcification de l'aorte qui est un modèle ex vivo de calcification cardiovasculaire (CCV). Nous avons montré que l'expression et l'activité de la PLD augmentent dans les Saos-2 et les ostéoblastes primaires au bout du 5ème jour de la différenciation tandis qu'elles s'accroissent au bout du 6ème jour de traitement de l'aorte dans un milieu d'hyperphosphatémie. Les inhibiteurs de PLD diminuent l'activité de phosphatase alcaline (TNAP) dans les ostéoblastes et dans l'aorte calcifiée tandis que la surexpression de la PLD1 dans les Saos-2 l'augmente. Dans une deuxième partie de ce travail, nous avons suivi la variation d'expression des récepteurs de PGE2 au cours de la maturation des Saos-2. L'expression du gène EP3 augmente au stade tardif de la minéralisation tandis que celle d'EP4 diminue. Pour conclure, ces résultats indiquent que l'activité de la PLD en affectant l'activité de la TNAP pourrait moduler finement la minéralisation physiologique et la CCV et que la minéralisation s'accompagne d'un changement d'expression des récepteurs de PGE2, dans les Saos-2

Lipid metabolism affects the maturation and the differentiation of bone cells. The aim of my PhD thesis is to explore two unknown sides of lipid metabolism which are the actions of phospholipase D (PLD) and those of prostaglandin PGE2 receptors during cell differentiation. Human lineage, Saos-2 cells and primary osteoblasts from calvaria of mice were used as cellular models of physiological mineralization. The ex vivo aorta culture under hyperphosphatemia conditions has been used to reproduce the calcification of the aorta, which is an ex vivo model of cardiovascular calcification (CVC). We showed that the expression and the activity of PLD increased in Saos-2 and primary osteoblasts after the fifth day of differentiation while in the aorta under hyperphosphatemia condition, PLD activity increased at the end of the sixth day. PLD inhibitors decreased the activity of alkaline phosphatase (TNAP) in osteoblasts and in calcified aorta while the overexpression of PLD1 in the Saos-2 increased it. In the second part of this work, we monitored the variation of the expression of PGE2 receptors during the maturation of Saos-2 cells. The EP3 gene expression increased in the late stage of the mineralization while that of EP4 decreased. In conclusion, these results indicated that the PLD activity by affecting the activity of TNAP could modulate the physiological mineralization and CVC. We showed that the…

Advisors/Committee Members: Buchet, René (thesis director), Hamade, Eva (thesis director), Badran, Bassam (thesis director), Mebarek, Saïda (thesis director).

Subjects/Keywords: Calcifications cardiovasculaire et physiologique; Phospholipase D; Récepteurs PGE2; Phosphatase alcaline; Physiological and cardiovascular calcifications; Phospholipase D; PGE2 receptors; Alkaline phosphatase; 572

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Abdallah, D. (2014). Fonctions de la phospholipase D et des récepteurs de la prostaglandine PGE2 durant la maturation des ostéoblastes, le processus de la minéralisation physiologique et la calcification cardiovasculaire : Functions of phospholipase D and PGE2 prostaglandin receptors during the maturation of osteoblasts, physiological mineralization and cardiovascular calcification process. (Doctoral Dissertation). Université Claude Bernard – Lyon I. Retrieved from http://www.theses.fr/2014LYO10152

Chicago Manual of Style (16^th Edition):

Abdallah, Dina. “Fonctions de la phospholipase D et des récepteurs de la prostaglandine PGE2 durant la maturation des ostéoblastes, le processus de la minéralisation physiologique et la calcification cardiovasculaire : Functions of phospholipase D and PGE2 prostaglandin receptors during the maturation of osteoblasts, physiological mineralization and cardiovascular calcification process.” 2014. Doctoral Dissertation, Université Claude Bernard – Lyon I. Accessed January 20, 2021. http://www.theses.fr/2014LYO10152.

MLA Handbook (7^th Edition):

Abdallah, Dina. “Fonctions de la phospholipase D et des récepteurs de la prostaglandine PGE2 durant la maturation des ostéoblastes, le processus de la minéralisation physiologique et la calcification cardiovasculaire : Functions of phospholipase D and PGE2 prostaglandin receptors during the maturation of osteoblasts, physiological mineralization and cardiovascular calcification process.” 2014. Web. 20 Jan 2021.

Vancouver:

Abdallah D. Fonctions de la phospholipase D et des récepteurs de la prostaglandine PGE2 durant la maturation des ostéoblastes, le processus de la minéralisation physiologique et la calcification cardiovasculaire : Functions of phospholipase D and PGE2 prostaglandin receptors during the maturation of osteoblasts, physiological mineralization and cardiovascular calcification process. [Internet] [Doctoral dissertation]. Université Claude Bernard – Lyon I; 2014. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2014LYO10152.

Council of Science Editors:

Abdallah D. Fonctions de la phospholipase D et des récepteurs de la prostaglandine PGE2 durant la maturation des ostéoblastes, le processus de la minéralisation physiologique et la calcification cardiovasculaire : Functions of phospholipase D and PGE2 prostaglandin receptors during the maturation of osteoblasts, physiological mineralization and cardiovascular calcification process. [Doctoral Dissertation]. Université Claude Bernard – Lyon I; 2014. Available from: http://www.theses.fr/2014LYO10152

9. Arhab, Yani. Caractérisation structurale et fonctionnelle des phospholipases D : Structural and functional characterization of phospholipases D.

Degree: Docteur es, Biochimie, 2018, Lyon

URL: http://www.theses.fr/2018LYSE1225

►

Les phospholipases D (PLD, EC 3.1.4.4) sont des enzymes ubiquitaires retrouvées aussi bien chez les procaryotes (bactéries) que chez les eucaryotes (plantes, animaux et champignons).… (more)

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Les phospholipases D (PLD, EC 3.1.4.4) sont des enzymes ubiquitaires retrouvées aussi bien chez les procaryotes (bactéries) que chez les eucaryotes (plantes, animaux et champignons). Les PLD catalysent l'hydrolyse des glycérophospholipides au niveau distal de la liaison phosphodiester pour former de l'acide phosphatidique, un important messager cellulaire impliqué dans de nombreuses voies telles que la prolifération cellulaire, la formation et le trafic vésiculaire, mais aussi la transcription et la survie cellulaire. Les PLD appartiennent à une superfamille de protéines (superfamille des PLD) qui ont en commun un site catalytique HXKX4D, X étant un acide aminé quelconque, contenant les résidus H (Histidyl), K (Lysyl) et D (Aspartyl). Ce site est nommé séquence consensus "HKD" et est dupliqué dans la plupart des membres de la superfamille des PLD. L'étude des PLD de plante est le moyen le plus sûr d'étudier cette famille d'enzyme car ce sont les seules PLD eucaryotiques purifiées à homogénéité et en grande quantité à ce jour. Ces travaux proposent une caractérisation fonctionnelle des résidus conservés au sein des PLD végétales menant à une caractérisation structurale avec la cristallisation de cette protéine. Dans un second temps l'activité de l'enzyme est modulée avec l'étude du domaine minimum, de la maturation post-traductionnelle de l'enzyme et le recherche d'un nouvel inhibiteur. Enfin, nous proposons le clonage d'une nouvelle PLD et la mise au point d'un système de détection in vivo de l'activité PLD

Phospholipases D (PLD, EC 3.1.4.4) are ubiquitary enzymes found in prokaryotes (bacteria) as well as in eukaryotes (plant, animals and fungi). PLD catalyzes the hydrolysis of the distal phosphoester bound of phospholipids thus forming phosphatidic acid, an important cell signaling messenger implicated in numerous pathways such as cell proliferation, vesicular formation and trafficking but also transcription and cell survival. PLDs belong to a superfamily of protein which share a common catalytic site called â€œHKDâ€ for HXKX4D, X is a random amino acid, containing H (Histidyl), K (lysyl) and D (aspartyl) residues. This consensus sequence is duplicated in most of the PLD superfamily members. The study of plant PLD is the best way to understand this family of proteins as they are the sole eukaryotic PLDs to be purified to homogeneity so far. This work provides a functional characterization of the most conserved residues in plant PLDs leading to a structural characterization with the crystallization of this enzyme. A second part of this work proposes the modulation of the enzyme hydrolysis activity by studying the minimal domain necessary for the activity and post-translational maturation undergone by plant PLDs. Also, we look for a new specific inhibitory molecule. Finally, we propose the cloning of a new plant PLD and the development of a new way to detect in vivo PLD activity

Advisors/Committee Members: Abousalham, Abdelkarim (thesis director), Noiriel, Alexandre (thesis director).

Subjects/Keywords: Phospholipase D; PLD; Structure; Fonction; Enzyme; Catalyse; Clonage; Modélisation; Phospholipase D; PLD; Structure; Function; Enzyme; Cloning; Modelisation; Catalysis; 570

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Arhab, Y. (2018). Caractérisation structurale et fonctionnelle des phospholipases D : Structural and functional characterization of phospholipases D. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2018LYSE1225

Chicago Manual of Style (16^th Edition):

Arhab, Yani. “Caractérisation structurale et fonctionnelle des phospholipases D : Structural and functional characterization of phospholipases D.” 2018. Doctoral Dissertation, Lyon. Accessed January 20, 2021. http://www.theses.fr/2018LYSE1225.

MLA Handbook (7^th Edition):

Arhab, Yani. “Caractérisation structurale et fonctionnelle des phospholipases D : Structural and functional characterization of phospholipases D.” 2018. Web. 20 Jan 2021.

Vancouver:

Arhab Y. Caractérisation structurale et fonctionnelle des phospholipases D : Structural and functional characterization of phospholipases D. [Internet] [Doctoral dissertation]. Lyon; 2018. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2018LYSE1225.

Council of Science Editors:

Arhab Y. Caractérisation structurale et fonctionnelle des phospholipases D : Structural and functional characterization of phospholipases D. [Doctoral Dissertation]. Lyon; 2018. Available from: http://www.theses.fr/2018LYSE1225

10. Tanguy, Emeline. Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée : Involvment of phosphatidic acid in membrane traffic : role and regulation of phospholipase D during phagocytosis and regulated exocytosis.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2019, Université de Strasbourg

URL: http://www.theses.fr/2019STRAJ112

►

La mise en évidence du rôle des lipides dans le trafic membranaire fait partie des avancées majeures de ces dernières années. Mes travaux de thèse… (more)

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La mise en évidence du rôle des lipides dans le trafic membranaire fait partie des avancées majeures de ces dernières années. Mes travaux de thèse se sont focalisés sur le plus simple des phospholipides, l’acide phosphatidique (PA). La production de PA par la phospholipase D (PLD) joue un rôle crucial au cours de la phagocytose et l’exocytose régulée, mais la dynamique de sa formation, tout comme les mécanismes d’action des différentes formes de PA, restent à ce jour totalement inconnus. Durant mon doctorat, j’ai contribué à la caractérisation de trois domaines de liaison peptidique au PA, qui nous ont permis de mieux comprendre les mécanismes d’interaction des protéines avec le PA et de générer des sondes moléculaires pour repérer ce lipide au sein des cellules. Ainsi, j’ai pu visualiser la production de PA au cours de la phagocytose et mis en évidence l’implication de la GTPase Arf6 dans la régulation de la synthèse de PA par la PLD. J’ai également pu montrer que la PLD est impliquée dans plusieurs étapes de l’exocytose dans des cellules neuroendocrines. Des expériences de lipidomique et de restauration ont révélé notamment que des formes mono- et polyinsaturées du PA contrôlent des étapes distinctes de l’exocytose que j’ai pu définir.

The discovery of the involvement of lipids in membrane trafficking is one of the major recent progress in cell biology. My thesis work focused on phosphatidic acid (PA), the simplest phospholipid. PA synthesis by phospholipase D (PLD) plays a crucial role during phagocytosis and regulated exocytosis, but its precise dynamics, as well as the mode of action of the different PA species, remain unknown. I characterized three PA binding domains allowing a better understanding of the interaction between proteins and PA and leading to the generation of genetic sensors for PA in cells. Thus I could visualize PA synthesis during phagocytosis and identified that the small GTPase Arf6 regulates PLD activity and consequently PA synthesis. My work also reveals that PLD modulates several steps during exocytosis in neuroendocrine cells. Further lipidomics and rescue experiments allowed me to show that mono- and polyunsaturated forms of PA are involved in distinct steps of exocytosis.

Advisors/Committee Members: Vitale, Nicolas (thesis director).

Subjects/Keywords: Acide phosphatidique; Phospholipase D; Trafic; Phagocytose; Exocytose; Lipides; Lipids; Neuroendocrine cell; Exocytosis; Phagocytosis; Phosphatidic acid; Phospholipase D; 572.4; 572.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tanguy, E. (2019). Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée : Involvment of phosphatidic acid in membrane traffic : role and regulation of phospholipase D during phagocytosis and regulated exocytosis. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2019STRAJ112

Chicago Manual of Style (16^th Edition):

Tanguy, Emeline. “Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée : Involvment of phosphatidic acid in membrane traffic : role and regulation of phospholipase D during phagocytosis and regulated exocytosis.” 2019. Doctoral Dissertation, Université de Strasbourg. Accessed January 20, 2021. http://www.theses.fr/2019STRAJ112.

MLA Handbook (7^th Edition):

Tanguy, Emeline. “Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée : Involvment of phosphatidic acid in membrane traffic : role and regulation of phospholipase D during phagocytosis and regulated exocytosis.” 2019. Web. 20 Jan 2021.

Vancouver:

Tanguy E. Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée : Involvment of phosphatidic acid in membrane traffic : role and regulation of phospholipase D during phagocytosis and regulated exocytosis. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2019. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2019STRAJ112.

Council of Science Editors:

Tanguy E. Implication de l’acide phosphatidique dans le trafic membranaire : rôle et régulation de la phospholipase D au cours de la phagocytose et de l’exocytose régulée : Involvment of phosphatidic acid in membrane traffic : role and regulation of phospholipase D during phagocytosis and regulated exocytosis. [Doctoral Dissertation]. Université de Strasbourg; 2019. Available from: http://www.theses.fr/2019STRAJ112

Vanderbilt University

11. Selvy, Paige Elizabeth. Mechanistic characterization of isoform selective inhibitors of mammalian phospholipase D.

Degree: PhD, Pharmacology, 2011, Vanderbilt University

URL: http://hdl.handle.net/1803/14456

► Increasing evidence supports an integral role for the lipid second messenger phosphatidic acid (PtdOH) in cell signaling. In addition to altering curvature of biological membranes,… (more)

Subjects/Keywords: small molecule inhibitor; phospholipase D; mechanism; interfacial kinetics; enzyme kinetics; lipids

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Selvy, P. E. (2011). Mechanistic characterization of isoform selective inhibitors of mammalian phospholipase D. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14456

Chicago Manual of Style (16^th Edition):

Selvy, Paige Elizabeth. “Mechanistic characterization of isoform selective inhibitors of mammalian phospholipase D.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/14456.

MLA Handbook (7^th Edition):

Selvy, Paige Elizabeth. “Mechanistic characterization of isoform selective inhibitors of mammalian phospholipase D.” 2011. Web. 20 Jan 2021.

Vancouver:

Selvy PE. Mechanistic characterization of isoform selective inhibitors of mammalian phospholipase D. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/14456.

Council of Science Editors:

Selvy PE. Mechanistic characterization of isoform selective inhibitors of mammalian phospholipase D. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/14456

Vanderbilt University

12. O'Reilly, Matthew Charles. Application of Organocatalysis to the Synthesis of Chiral Morpholines, Piperazines, Aziridines, Azetidines, beta-fluoroamines, and gamma-fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties.

Degree: PhD, Chemistry, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/12701

► My doctoral research has focused on (i) using organocatalysis to prepare enantioenriched pharmaceutically relevant scaffolds and (ii) preparing isoenzyme selective inhibitors of phospholipase D. (i)… (more)

▼ My doctoral research has focused on (i) using organocatalysis to prepare enantioenriched pharmaceutically relevant scaffolds and (ii) preparing isoenzyme selective inhibitors of phospholipase D. (i) Methodologies for asymmetric chlorination and fluorination of aldehydes have recently been reported; the potential of such building blocks in organic synthesis, however, were yet be exploited. We sought to fully unveil the synthetic potential of enantioenriched chlorinated and fluorinated aldehydes or alcohols as chiral building blocks toward the synthesis of various pharmaceutically relevant scaffolds. Morpholines, piperazines, azetidines, and aziridines are biologically relevant scaffolds and are often used as important synthetic intermediates. These scaffolds, however, are often difficult to prepare in enantioenriched form. By utilizing organocatalysis to arrive at chiral β-chloro alcohols, I was able to generate all of these scaffolds through a novel and facile manifold of reactions in good overall yields and excellent enantiomeric excess. Importantly, these synthetic methods provide access to these enantioenriched scaffolds from achiral aldehydes, of which hundreds are commercially available. In a similar vein, we found that organocatalytic asymmetric fluorination methods provide access to fluoro-aldehydes from achiral aldehydes. Fluorination is a common method used to improve a compounds metabolic stability, bioavailability, ancillary pharmacology profile, protein-ligand interactions, and CNS exposure. Using organocatalysis to generate enantioenriched β-fluoro alcohols, I was able to utilize a general reaction pathway towards chiral fluorinated scaffolds of pharmaceutical relevance. Of note, the chiral fluorinated scaffolds would have previously been accessed through alternate chemistry that is frequently plagued with low yields, rearrangements, and dehydration products. Our method offers a considerable advantage compared to past literature precedent. (ii) Phospholipase D (PLD)—an enzyme that catalyzes the hydrolysis of phosphatidyl choline to phosphatidic acid (PA)—has two mammalian isoforms that share 53% sequence homology. PA is a lipid second messenger involved in various signaling cascades. Aberrant PLD activity—and atypical PA concentrations—have been implicated in a number of human diseases. Until recently, there were no ways to chemically modulate either PLD isoenzyme selectively; therefore, it was difficult to distinguish between phenotypes driven by aberrant PLD1 or PLD2 activity. Prior to my work, a highly potent and selective PLD1 inhibitor was discovered in the Lindsley lab, but PLD2 inhibitors with enhanced selectivity profiles remained highly desirable. Therefore, we began a medicinal chemistry campaign to discover selective PLD2 inhibitors with improved physiochemical and DMPK properties. This effort produced compounds with enhanced potency and selectivity. Moreover, a key stereocenter was identified during the process that immensely increases PLD1 potency with IC50 amplifications of 200 to… Advisors/Committee Members: H. Alex Brown (committee member), Brian Bachmann (committee member), Gary Sulikowski (committee member), Craig Lindsley (Committee Chair).

Subjects/Keywords: piperazines; morpholines; Phospholipase D; organocatalysis; fluoroamines; aziridines; azetidines

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

O'Reilly, M. C. (2014). Application of Organocatalysis to the Synthesis of Chiral Morpholines, Piperazines, Aziridines, Azetidines, beta-fluoroamines, and gamma-fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12701

Chicago Manual of Style (16^th Edition):

O'Reilly, Matthew Charles. “Application of Organocatalysis to the Synthesis of Chiral Morpholines, Piperazines, Aziridines, Azetidines, beta-fluoroamines, and gamma-fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/12701.

MLA Handbook (7^th Edition):

O'Reilly, Matthew Charles. “Application of Organocatalysis to the Synthesis of Chiral Morpholines, Piperazines, Aziridines, Azetidines, beta-fluoroamines, and gamma-fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties.” 2014. Web. 20 Jan 2021.

Vancouver:

O'Reilly MC. Application of Organocatalysis to the Synthesis of Chiral Morpholines, Piperazines, Aziridines, Azetidines, beta-fluoroamines, and gamma-fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/12701.

Council of Science Editors:

O'Reilly MC. Application of Organocatalysis to the Synthesis of Chiral Morpholines, Piperazines, Aziridines, Azetidines, beta-fluoroamines, and gamma-fluoroamines; Discovery of Selective Phospholipase D Inhibitors with Optimized in vivo Properties. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/12701

Vanderbilt University

13. Bruntz, Ronald Chase. Insights into the Molecular Mechanisms of Phospholipase D-Mediated Cancer Cell Survival.

Degree: PhD, Pharmacology, 2014, Vanderbilt University

URL: http://hdl.handle.net/1803/10427

► The production of bioactive lipids by phospholipases has long been appreciated as an important mode of cellular communication. Phospholipase D (PLD) enzymes hydrolyze phosphatidylcholine to… (more)

Subjects/Keywords: phospholipase D; phosphatidic acid; cancer; Akt; cell signaling; autophagy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bruntz, R. C. (2014). Insights into the Molecular Mechanisms of Phospholipase D-Mediated Cancer Cell Survival. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10427

Chicago Manual of Style (16^th Edition):

Bruntz, Ronald Chase. “Insights into the Molecular Mechanisms of Phospholipase D-Mediated Cancer Cell Survival.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021. http://hdl.handle.net/1803/10427.

MLA Handbook (7^th Edition):

Bruntz, Ronald Chase. “Insights into the Molecular Mechanisms of Phospholipase D-Mediated Cancer Cell Survival.” 2014. Web. 20 Jan 2021.

Vancouver:

Bruntz RC. Insights into the Molecular Mechanisms of Phospholipase D-Mediated Cancer Cell Survival. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1803/10427.

Council of Science Editors:

Bruntz RC. Insights into the Molecular Mechanisms of Phospholipase D-Mediated Cancer Cell Survival. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/10427

14. TAY HWEE KEE. Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells.

Degree: 2007, National University of Singapore

URL: http://scholarbank.nus.edu.sg/handle/10635/15636

Subjects/Keywords: FcgRÐ†; FceRÐ†; Phospholipase A2; Phospholipase D; Sphingosine kinase; Signaling

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

KEE, T. H. (2007). Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/15636

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

KEE, TAY HWEE. “Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells.” 2007. Thesis, National University of Singapore. Accessed January 20, 2021. http://scholarbank.nus.edu.sg/handle/10635/15636.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

KEE, TAY HWEE. “Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells.” 2007. Web. 20 Jan 2021.

Vancouver:

KEE TH. Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells. [Internet] [Thesis]. National University of Singapore; 2007. [cited 2021 Jan 20]. Available from: http://scholarbank.nus.edu.sg/handle/10635/15636.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

KEE TH. Dissecting the phospholipid signaling pathways triggered by Fc receptors in human immune effector cells. [Thesis]. National University of Singapore; 2007. Available from: http://scholarbank.nus.edu.sg/handle/10635/15636

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

15. Skafi, Najwa. Role of Phospholipase D in Vascular Calcification : Le rôle de la phospholipase D dans la calcification vasculaire.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2017, Lyon; Université libanaise

URL: http://www.theses.fr/2017LYSE1339

► La calcification vasculaire est l’accumulation de cristaux de calcium dans les vaisseaux sanguins à travers un processus pathologique qui ressemble à la formation de l’os… (more)

▼ La calcification vasculaire est l’accumulation de cristaux de calcium dans les vaisseaux sanguins à travers un processus pathologique qui ressemble à la formation de l’os ou du cartilage. Elle apparaît notamment chez les patients diabétiques ou atteints d’une insuffisance rénale chronique. La conséquence principale de la calcification vasculaire est la perte de l’élasticité qui est indispensable pour la fonction des larges artères, elle est de plus associée à la mortalité des patients hémodialysés. Les traitements contre la calcification vasculaire sont généralement limités à ceux qui corrigent les facteurs causatifs des problèmes de santé mais aucune intervention efficace, spécifique et ciblée n’est disponible. Par conséquence, une compréhension profonde des mécanismes moléculaires impliqués dans la calcification vasculaire est nécessaire dans le but de trouver de nouvelles cibles thérapeutiques. La phospholipase D catalyse l’hydrolyse des phospholipides en acide phosphatidique et une tête polaire, elle est aussi impliquée dans différentes fonctions cellulaires et maladies. Il a été démontré qu’elle peut être activée par des facteurs impliqués dans l’ostéogenèse et par d’autres impliqués dans la calcification vasculaire. Ainsi, nous avons étudié le rôle de la phospholipase D dans la calcification vasculaire dans 3 modèles différents. Le premier est un modèle in-vitro de cellules musculaires lisses murines (lignée cellulaire MOVAS), elles sont cultivées en présence d’acide ascorbique et de β-glycérophosphate. Le deuxième est un modèle ex-vivo d’explants d’aortes cultivés en présence de fortes concentrations de phosphate et le troisième est un modèle in-vivo d’insuffisance rénale chronique produite chez des rats. Dans ce dernier modèle, la calcification vasculaire est induite par un régime riche en phosphore et en calcium et par des injections de vitamine D active. La calcification dans ces trois modèles a été suivie par l’analyse de la minéralisation en dosant les dépôts de calcium, de l’activité phosphatase alcaline, et de l’expression de différents marqueurs ostéo-chondrocytaires. Une augmentation de l’expression génique de Pld1 a été observée dans les trois modèles, en particulier au cours des premières étapes de la calcification, et a été accompagnée d'une activité accrue de la phospholipase D dans les modèles in vitro et ex-vivo. L’inhibition de l’activité phospholipase D dans ces deux modèles ou de la phospholipase D1 dans le modèle MOVAS a bloqué complètement la calcification. Par contre, l’inhibition spécifique de la phospholipase D2 n’a pas montré des effets significatifs. Deux voies par lesquelles la phospholipase D peut être activée ont été testées, la voie de la protéine kinase C et la voie de la sphingosine-1-phosphate. Ces deux voies métaboliques se sont révélées être impliquées dans le processus de calcification mais pas forcément dans l’activation de la phospholipase D au cours de ce processus. Des résultats préliminaires ont montré que la phospholipase D pourrait agir après activation de la… Advisors/Committee Members: Mebarek, Saïda (thesis director), Brizuela Madrid, Leyre (thesis director), Badran, Bassam (thesis director), Hussein, Nader (thesis director).

Subjects/Keywords: Phospholipase D; Calcification vasculaire; Phosphatase alcaline; Cellules musculaires lisses; Insuffisance rénale chronique; Aorte; Phospholipase D; Vascular calcification; Alkaline phosphatase; Smooth muscle cells; Chronic kidney disease; Aorta; 571.6

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Skafi, N. (2017). Role of Phospholipase D in Vascular Calcification : Le rôle de la phospholipase D dans la calcification vasculaire. (Doctoral Dissertation). Lyon; Université libanaise. Retrieved from http://www.theses.fr/2017LYSE1339

Chicago Manual of Style (16^th Edition):

Skafi, Najwa. “Role of Phospholipase D in Vascular Calcification : Le rôle de la phospholipase D dans la calcification vasculaire.” 2017. Doctoral Dissertation, Lyon; Université libanaise. Accessed January 20, 2021. http://www.theses.fr/2017LYSE1339.

MLA Handbook (7^th Edition):

Skafi, Najwa. “Role of Phospholipase D in Vascular Calcification : Le rôle de la phospholipase D dans la calcification vasculaire.” 2017. Web. 20 Jan 2021.

Vancouver:

Skafi N. Role of Phospholipase D in Vascular Calcification : Le rôle de la phospholipase D dans la calcification vasculaire. [Internet] [Doctoral dissertation]. Lyon; Université libanaise; 2017. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2017LYSE1339.

Council of Science Editors:

Skafi N. Role of Phospholipase D in Vascular Calcification : Le rôle de la phospholipase D dans la calcification vasculaire. [Doctoral Dissertation]. Lyon; Université libanaise; 2017. Available from: http://www.theses.fr/2017LYSE1339

16. Wang, Qili. Interaction entre la sous unité V0 de la V-ATPase et le facteur d'échange ARNO et son implication fonctionnelle dans l'exocytose régulée : Interaction between the V0 subunit of V-ATPase and the exchange factor ARNO and its functional involvement in regulated exocytosis.

Degree: Docteur es, Neurosciences, 2019, Université de Strasbourg

URL: http://www.theses.fr/2019STRAJ049

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Alors que s’accumulent des données épidémiologiques qui suggèrent une importance fondamentale des lipides de l’alimentation dans l’homéostasie cellulaire et le développement de nombreuses pathologies humaines,… (more)

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Alors que s’accumulent des données épidémiologiques qui suggèrent une importance fondamentale des lipides de l’alimentation dans l’homéostasie cellulaire et le développement de nombreuses pathologies humaines, peu d’informations sur leurs fonctions spécifiques sont disponibles à ce jour. Ceci est particulièrement le cas pour la neurosecrétion qui dépend de la fusion d’organites vésiculaires avec la membrane plasmique. Des études récentes ont montré le rôle clé de la compartimentalisation lipidique au niveau des sites d’exocytose et par ailleurs validées la notion de lipides fusogéniques, comme pour l’acide phosphatidique (PA).La V-ATPase, via ses domaines V0 et V1 est à la fois impliquée dans le remplissage en neurotransmetteurs des vésicules, mais aussi dans leur fusion. Nous montrons ici que V0a1 interagit avec le facteur d’échange pour Arf6 ARNO. En bloquant cette interaction, nous avons observé une réduction de l’activation d’Arf6, de l’activité PLD et de l’exocytose, avec une modification de la cinétique des événements unitaires d’exocytose. Nous proposons que la dissociation de V1 de V0 pourrait représenter un signal permettant l’activation de la voie Arf6-ARNO-PLD1 et ainsi promouvoir la synthèse de PA requise à une exocytose efficace dans les cellules neuroendocrines.

Lipids play key cellular functions and are involved in many human diseases and little information is available on their exact function. This is especially the case in neurosecretion that relies on the fusion of specific membrane organelle with the plasma membrane for which relatively little attention has been paid to the necessary role of lipids. Recent studies have established the importance of lipid compartmentalization at the exocytotic sites and validated the contribution of fusogenic lipids such as phosphatidic acid (PA) for membrane fusion. The V-ATPase is involved both in the charging of secretory vesicle and the membrane fusion for secretion of vesicle. Indeed, the V1 and V0 subdomains were shown to dissociate during stimulation allowing subunits of the vesicular V0 to interact with different proteins of the secretory machinery. We show here that V0a1 interacts with the exchange factor ARNO and promotes Arf6 activation during exocytosis in neuroendocrine cells. Interfering with the V0a1-ARNO interaction prevented phospholipase D (PLD) activation, phosphatidic acid synthesis during exocytosis, and altered the kinetic parameters of individual fusion events.We suggest that V1 dissociation from V0 could represent the signal that triggers the activation of the ARNO-Arf6-PLD1 pathway and promotes PA synthesis needed for efficient exocytosis in neuroendocrine cells.

Advisors/Committee Members: Vitale, Nicolas (thesis director).

Subjects/Keywords: Acide phosphatidique; Cellule neuroendocrine; Lipides; Phospholipase D; Exocytose; V-ATPase; Exocytosis; Lipids; Neuroendocrine cell; Phosphatidic acid; Phospholipase D; V-ATPase; 572.4; 616.8

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wang, Q. (2019). Interaction entre la sous unité V0 de la V-ATPase et le facteur d'échange ARNO et son implication fonctionnelle dans l'exocytose régulée : Interaction between the V0 subunit of V-ATPase and the exchange factor ARNO and its functional involvement in regulated exocytosis. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2019STRAJ049

Chicago Manual of Style (16^th Edition):

Wang, Qili. “Interaction entre la sous unité V0 de la V-ATPase et le facteur d'échange ARNO et son implication fonctionnelle dans l'exocytose régulée : Interaction between the V0 subunit of V-ATPase and the exchange factor ARNO and its functional involvement in regulated exocytosis.” 2019. Doctoral Dissertation, Université de Strasbourg. Accessed January 20, 2021. http://www.theses.fr/2019STRAJ049.

MLA Handbook (7^th Edition):

Wang, Qili. “Interaction entre la sous unité V0 de la V-ATPase et le facteur d'échange ARNO et son implication fonctionnelle dans l'exocytose régulée : Interaction between the V0 subunit of V-ATPase and the exchange factor ARNO and its functional involvement in regulated exocytosis.” 2019. Web. 20 Jan 2021.

Vancouver:

Wang Q. Interaction entre la sous unité V0 de la V-ATPase et le facteur d'échange ARNO et son implication fonctionnelle dans l'exocytose régulée : Interaction between the V0 subunit of V-ATPase and the exchange factor ARNO and its functional involvement in regulated exocytosis. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2019. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2019STRAJ049.

Council of Science Editors:

Wang Q. Interaction entre la sous unité V0 de la V-ATPase et le facteur d'échange ARNO et son implication fonctionnelle dans l'exocytose régulée : Interaction between the V0 subunit of V-ATPase and the exchange factor ARNO and its functional involvement in regulated exocytosis. [Doctoral Dissertation]. Université de Strasbourg; 2019. Available from: http://www.theses.fr/2019STRAJ049

17. 喜田, 孝史. 新規リン脂質、フィトセラミド 1-リン酸の生合成経路と代謝、および生成酵素の解析.

Degree: 博士（薬科学）, 2017, Tokushima University / 徳島大学

URL: http://repo.lib.tokushima-u.ac.jp/110930

Subjects/Keywords: Glycosyl-inositolphosphoceramide; Phospholipase D; Plants; Sphingophospholipid

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

喜田, �. (2017). 新規リン脂質、フィトセラミド 1-リン酸の生合成経路と代謝、および生成酵素の解析. (Thesis). Tokushima University / 徳島大学. Retrieved from http://repo.lib.tokushima-u.ac.jp/110930

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

喜田, 孝史. “新規リン脂質、フィトセラミド 1-リン酸の生合成経路と代謝、および生成酵素の解析.” 2017. Thesis, Tokushima University / 徳島大学. Accessed January 20, 2021. http://repo.lib.tokushima-u.ac.jp/110930.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

喜田, 孝史. “新規リン脂質、フィトセラミド 1-リン酸の生合成経路と代謝、および生成酵素の解析.” 2017. Web. 20 Jan 2021.

Vancouver:

喜田 �. 新規リン脂質、フィトセラミド 1-リン酸の生合成経路と代謝、および生成酵素の解析. [Internet] [Thesis]. Tokushima University / 徳島大学; 2017. [cited 2021 Jan 20]. Available from: http://repo.lib.tokushima-u.ac.jp/110930.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

喜田 �. 新規リン脂質、フィトセラミド 1-リン酸の生合成経路と代謝、および生成酵素の解析. [Thesis]. Tokushima University / 徳島大学; 2017. Available from: http://repo.lib.tokushima-u.ac.jp/110930

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Boston College

18. Cai, Jingfei. Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C.

Degree: PhD, Chemistry, 2013, Boston College

URL: http://dlib.bc.edu/islandora/object/bc-ir:101804

► Peripheral proteins from mammals often exhibit multi-domain structures and require metal ions such as calcium as co-factors. This dissertation investigates two types of such proteins… (more)

Subjects/Keywords: EF-hand domain; mammalian phospholipase C; model membrane; surfactant protein A; surfactant protein D

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cai, J. (2013). Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C. (Doctoral Dissertation). Boston College. Retrieved from http://dlib.bc.edu/islandora/object/bc-ir:101804

Chicago Manual of Style (16^th Edition):

Cai, Jingfei. “Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C.” 2013. Doctoral Dissertation, Boston College. Accessed January 20, 2021. http://dlib.bc.edu/islandora/object/bc-ir:101804.

MLA Handbook (7^th Edition):

Cai, Jingfei. “Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C.” 2013. Web. 20 Jan 2021.

Vancouver:

Cai J. Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C. [Internet] [Doctoral dissertation]. Boston College; 2013. [cited 2021 Jan 20]. Available from: http://dlib.bc.edu/islandora/object/bc-ir:101804.

Council of Science Editors:

Cai J. Probing the Membrane Association Mechanisms for Pulmonary Collectins and Mammalian Phospholipase C. [Doctoral Dissertation]. Boston College; 2013. Available from: http://dlib.bc.edu/islandora/object/bc-ir:101804

University of Melbourne

19. Li, Meina. A novel non-canonical pathway with potential for safer modulation of TGF-beta1 in steroid-resistant airway diseases.

Degree: 2017, University of Melbourne

URL: http://hdl.handle.net/11343/208016

► Glucocorticoids remain central to treatment regimens for chronic airway inflammatory diseases, but the therapeutic responses are often limited by impaired responses in severe diseases. Glucocorticoid… (more)

▼ Glucocorticoids remain central to treatment regimens for chronic airway inflammatory diseases, but the therapeutic responses are often limited by impaired responses in severe diseases. Glucocorticoid activity can be negatively regulated by the inflammatory microenvironment. Of the mechanisms investigated to date, the glucocorticoid insensitivity caused by transforming growth factor (TGF-beta1) in airway epithelium demands most attention, because of its extraordinary capacity at the pathophysiologically relevant picomolar concentrations to ablate glucocorticoid activity, as well as acting as a key mediator of viral infection-induced glucocorticoid insensitivity. Global inhibition of TGF-beta1 carries known risks, including autoimmune diseases, increased cancer risks and mitral valve defects. Therefore, the identification of signals downstream of TGF-beta1 receptors, through which TGF-beta1 suppresses glucocorticoid activity may provide novel and safe therapeutic targets to improve glucocorticoid effectiveness in inflammatory airway diseases. Data presented within this thesis has provided evidence that TGF-beta1 has a broad suppressive effect in impact on the glucocorticoid transcriptome. Hypothesis-free proteomic analysis of airway epithelial cells identified 24 candidate mediators from which an increase in the levels of phosphorylated cofilin1 was prioritized for analysis, because: cofilin1 phosphorylation was not inhibited by a cocktail of small molecule inhibitors of non-canonical kinases; and, cofilin1 phosphorylation was induced by TGF-beta1 and TGF-beta3 which impair glucocorticoid activity, but not by TGF-beta2 which has no effect on glucocorticoid activity. Pharmacological and genetic approaches established that TGF-beta1-induced glucocorticoid insensitivity is mediated by a novel signaling cascade involving LIM domain kinase 2 (LIMK2)-mediated phosphorylation of cofilin1. Phospho-cofilin1 activates phospholipase D (PLD) to generate the effectors (lyso)phosphatidic acid (PA). These PLD products mediate the TGF-beta1-induced glucocorticoid insensitivity, causing the impairment of both glucocorticoid inducible GRE activity and endogenous gene expression. Data obtained during these thesis studies identified that inhibition the CLOCK regulator casein kinase 1delta/epsilon (CK1delta/epsilon) represents a promising strategy for targeted treatment in inflammatory pulmonary diseases with TGF-beta1 involvement. We have shown that pharmacological inhibition of CK1delta/epsilon reduced TGF-beta1-induced fibrogenic signals, and also attenuated TGF-beta1 signals subserving glucocorticoid insensitivity. In addition, inhibition of CK1delta/epsilon suppressed inflammogen-induced inflammatory cytokine production by airway epithelial cells. This study has provided extensive evidence that TGF-beta1 has broad impact on the glucocorticoid transcriptome. Furthermore, through the systematic investigation into the underlying mechanisms through which this insensitivity is induced, this study has provided novel insights into…

Subjects/Keywords: TGF-beta1; glucocorticoid insensitivity; phospho-cofilin1; LIM kinase; phospholipase D; (lyso)phosphatidic acid

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Li, M. (2017). A novel non-canonical pathway with potential for safer modulation of TGF-beta1 in steroid-resistant airway diseases. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/208016

Chicago Manual of Style (16^th Edition):

Li, Meina. “A novel non-canonical pathway with potential for safer modulation of TGF-beta1 in steroid-resistant airway diseases.” 2017. Doctoral Dissertation, University of Melbourne. Accessed January 20, 2021. http://hdl.handle.net/11343/208016.

MLA Handbook (7^th Edition):

Li, Meina. “A novel non-canonical pathway with potential for safer modulation of TGF-beta1 in steroid-resistant airway diseases.” 2017. Web. 20 Jan 2021.

Vancouver:

Li M. A novel non-canonical pathway with potential for safer modulation of TGF-beta1 in steroid-resistant airway diseases. [Internet] [Doctoral dissertation]. University of Melbourne; 2017. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/11343/208016.

Council of Science Editors:

Li M. A novel non-canonical pathway with potential for safer modulation of TGF-beta1 in steroid-resistant airway diseases. [Doctoral Dissertation]. University of Melbourne; 2017. Available from: http://hdl.handle.net/11343/208016

University of North Texas

20. Brown, Shea Austin. N-Acylethanolamines and Plant Phospholipase D.

Degree: 1998, University of North Texas

URL: https://digital.library.unt.edu/ark:/67531/metadc279270/

► Recently, three distinct isoforms of phospholipase D (PLD) were identified in Arabidopsis thaliana. PLD α represents the well-known form found in plants, while PLD β… (more)

Subjects/Keywords: phospholipase D; plants; biochemistry; Phospholipases.; Phospholipids.

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APA (6^th Edition):

Brown, S. A. (1998). N-Acylethanolamines and Plant Phospholipase D. (Thesis). University of North Texas. Retrieved from https://digital.library.unt.edu/ark:/67531/metadc279270/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Brown, Shea Austin. “N-Acylethanolamines and Plant Phospholipase D.” 1998. Thesis, University of North Texas. Accessed January 20, 2021. https://digital.library.unt.edu/ark:/67531/metadc279270/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Brown, Shea Austin. “N-Acylethanolamines and Plant Phospholipase D.” 1998. Web. 20 Jan 2021.

Vancouver:

Brown SA. N-Acylethanolamines and Plant Phospholipase D. [Internet] [Thesis]. University of North Texas; 1998. [cited 2021 Jan 20]. Available from: https://digital.library.unt.edu/ark:/67531/metadc279270/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Brown SA. N-Acylethanolamines and Plant Phospholipase D. [Thesis]. University of North Texas; 1998. Available from: https://digital.library.unt.edu/ark:/67531/metadc279270/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Kansas State University

21. Lee, Jung Hoon. Suppression of phospholipase D[Alpha] in soybean.

Degree: PhD, Department of Agronomy, 2008, Kansas State University

URL: http://hdl.handle.net/2097/828

► Demands on value-added crops have been raised to improve agricultural, industrial, and economical value. Currently, transgene application is one of most effective methods to satisfy… (more)

▼ Demands on value-added crops have been raised to improve agricultural, industrial, and economical value. Currently, transgene application is one of most effective methods to satisfy these demands. Success in herbicide-resistant soybean (Glycine max (L.) Merr.) has boosted genetic engineering to be used for biochemical, nutritional, cultural, and physiological improvements. The objectives of this study were to establish transgenic soybean lines with attenuated phospholipase D[Alpha] (PLD[Alpha]) activity in the seed, test the alteration of fatty acid profiles affected by transgene and somaclonal variation, and evaluate the physiological alteration of transgenic lines by both transgene and somaclonal variation. To change fatty acid profile in soybean seed, we attenuated PLD[Alpha] enzyme activity by an RNA interference construct using the PLD[Alpha] gene sequence. Two transgenic soybean lines were established by particle inflow gun bombardment of co-bombarding pSPLDi and pHG1 transgenes, and evaluated for the presence and expression of transgenes thoroughly through the T[subscript]5 generation. PLDα-suppressed soybean lines were characterized by decreased PLD[Alpha] enzyme activity and PLD[Alpha] protein both during seed development and in mature seeds. The PLD[Alpha]-attenuated transgenic lines, SW1-7-1-1 and SW1-7-1-2, contain 36% and 49% oleic acid in the filed and greenhouse evaluations, respectively, which are equivalent to the mid-oleic acid soybean lines improved by conventional breeding and mutagenesis. Phenotypic and genetic analysis of the transgenic lines suggested the possibility that the multi-copy transgene integration formed direct or indirect repeats by random ligation during integration and organization of transgenes in the soybean genome, and the transgene cluster with tandem repeats may consequently increase the probability of transgene silencing. Various factors, such as high humidity and temperature, result in the loss of seed viability. Fayette seed stored for two months since harvest exhibited about 95% viability; however Fayette seeds stored for 33 months at room temperature and uncontrolled relative humidity become non-viable. PLDα-attenuated transgenic soybean seeds have been produced by transformation. PLD-suppressed transgenic soybean seeds have maintained viability when stored for 33 months at room temperature. Germination of transgenic seed stored for 33 months ranged from 30 to 50%. Increased leakage of electrolytes associated with the loss of viability was observed in null-transgenic and background seeds versus transgenic seed. The increase in electrolyte leakage may have been induced by lipid peroxidation and free radical formation which can generate oxidative damage in the cell and subsequently decrease seed viability. Differences in the ultrastructure of cotyledon tissue were observed between PLD[Alpha]-suppressed soybean and the background cultivar. The loss of viability in the background cultivar was consistent with observations of the plasma membrane being detached from the cell… Advisors/Committee Members: William T. Schapaugh JrHarold N. Trick.

Subjects/Keywords: soybean; phospholipase D; Agriculture, Agronomy (0285)

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lee, J. H. (2008). Suppression of phospholipase D[Alpha] in soybean. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/828

Chicago Manual of Style (16^th Edition):

Lee, Jung Hoon. “Suppression of phospholipase D[Alpha] in soybean.” 2008. Doctoral Dissertation, Kansas State University. Accessed January 20, 2021. http://hdl.handle.net/2097/828.

MLA Handbook (7^th Edition):

Lee, Jung Hoon. “Suppression of phospholipase D[Alpha] in soybean.” 2008. Web. 20 Jan 2021.

Vancouver:

Lee JH. Suppression of phospholipase D[Alpha] in soybean. [Internet] [Doctoral dissertation]. Kansas State University; 2008. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2097/828.

Council of Science Editors:

Lee JH. Suppression of phospholipase D[Alpha] in soybean. [Doctoral Dissertation]. Kansas State University; 2008. Available from: http://hdl.handle.net/2097/828

22. Rahier-Corticchiato, Renaud. Caractérisation biochimique des phospholipases D et de leurs domaines fonctionnels : nouvelle méthode de mesure de l’activité phospholipase D : Biochemical characterization of phospholipases D and their functional domains : novel method for measuring phospholipase D activities.

Degree: Docteur es, Biochimie, 2016, Lyon

URL: http://www.theses.fr/2016LYSE1292

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La phospholipase D (PLD) hydrolyse les phospholipides membranaires en libérant leur tête polaire afin de générer l'acide phosphatidique (PA), impliqué dans la signalisation cellulaire. Pour… (more)

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La phospholipase D (PLD) hydrolyse les phospholipides membranaires en libérant leur tête polaire afin de générer l'acide phosphatidique (PA), impliqué dans la signalisation cellulaire. Pour comprendre les propriétés biochimiques des PLDs, les travaux présentés ont été réalisés autour de deux axes. Le premier axe concerne l'expression recombinante et la purification de la PLDa d'Arabidopsis thaliana (AtPLDa) dans la levure Pichia pastoris. La détermination de la séquence N-terminale a révélé que l'AtPLDa est amputée de ses 35 premiers résidus, suggérant ainsi la participation d'un mécanisme de maturation. Cependant, la région N-terminale des PLDs de plantes est homologue au domaine C2, impliqué dans leur interaction Ca2+-dépendante avec la membrane. Afin d'évaluer l'impact d'un tel clivage, les domaines C2 de l'AtPLDa mais également de l'AtPLDß, à titre de comparaison, ont été étudiés sous leur forme entière ou mature. Ainsi, la caractérisation de leur affinité pour les phospholipides, associée à leur modélisation tridimensionnelle, ont permis de démontrer que les différences de régulation par le Ca2+, observées entre les formes entières et mature, provenait de la présence d'une hélice a amphipathique, retirée lors du processus de maturation. Le second axe concerne le développement d'une nouvelle méthode de mesure des activités PLD via le dosage de manière direct, spécifique et continu du PA grâce à la propriété d'amplification de fluorescence par chélation de la 8-hydroxyquinoléine, en présence de Ca2+. Ainsi, ce test apparait adapté pour le suivi de l'inhibition des PLDs et pour l'étude de leur spécificité de substrat, en utilisant des phospholipides naturels avec différentes tête polaires, et à l'échelle d'une microplaque

Phospholipase D (PLD) hydrolyses membrane phospholipids, leading to the formation of free polar headgroup and phosphatidic acid releasing, involved in cell signaling. To understand the biochemical properties of PLDs, this work has been made around two axes. The one first concerns the recombinant expression and purification of the PLDa of Arabidopsis thaliana (AtPLDa) in the yeast Pichia pastoris. The N-terminal sequence of the recombinant AtPLDa has been determined and found to lack its first 35 amino acids, suggesting the involvement of a maturing mechanism. However, plant PLDs exhibit a C2-lipid binding domain at their N-terminal region, which is involved in their Ca2+-dependent membrane targeting. Thus, to assess the impact of such a cleavage, whole and mature-like C2 domains of AtPLDa, as well as of AtPLDß, for the sake of comparison were studied. Thus, the characterization of their affinity for phospholipids, combined with their three-dimensional modeling have demonstrated that the differences observed in their regulation by Ca2+, observed between whole and mature-like forms, originated from the presence of a N-terminus amphipathic a helix, removed during the maturation process. The second axis concerns the development of a novel PLD assay that measure PA in a direct, specific and…

Advisors/Committee Members: Abousalham, Abdelkarim (thesis director), Noiriel, Alexandre (thesis director).

Subjects/Keywords: Phospholipases D; Domaine C2; Arabidopsis thaliana; Pichia pastoris; 8-Hydroxyquinoléine; Phospholipase D; C2 domains; Arabidopsis thaliana; Pichia pastoris; 8-hydroxyquinoline; 572

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rahier-Corticchiato, R. (2016). Caractérisation biochimique des phospholipases D et de leurs domaines fonctionnels : nouvelle méthode de mesure de l’activité phospholipase D : Biochemical characterization of phospholipases D and their functional domains : novel method for measuring phospholipase D activities. (Doctoral Dissertation). Lyon. Retrieved from http://www.theses.fr/2016LYSE1292

Chicago Manual of Style (16^th Edition):

Rahier-Corticchiato, Renaud. “Caractérisation biochimique des phospholipases D et de leurs domaines fonctionnels : nouvelle méthode de mesure de l’activité phospholipase D : Biochemical characterization of phospholipases D and their functional domains : novel method for measuring phospholipase D activities.” 2016. Doctoral Dissertation, Lyon. Accessed January 20, 2021. http://www.theses.fr/2016LYSE1292.

MLA Handbook (7^th Edition):

Rahier-Corticchiato, Renaud. “Caractérisation biochimique des phospholipases D et de leurs domaines fonctionnels : nouvelle méthode de mesure de l’activité phospholipase D : Biochemical characterization of phospholipases D and their functional domains : novel method for measuring phospholipase D activities.” 2016. Web. 20 Jan 2021.

Vancouver:

Rahier-Corticchiato R. Caractérisation biochimique des phospholipases D et de leurs domaines fonctionnels : nouvelle méthode de mesure de l’activité phospholipase D : Biochemical characterization of phospholipases D and their functional domains : novel method for measuring phospholipase D activities. [Internet] [Doctoral dissertation]. Lyon; 2016. [cited 2021 Jan 20]. Available from: http://www.theses.fr/2016LYSE1292.

Council of Science Editors:

Rahier-Corticchiato R. Caractérisation biochimique des phospholipases D et de leurs domaines fonctionnels : nouvelle méthode de mesure de l’activité phospholipase D : Biochemical characterization of phospholipases D and their functional domains : novel method for measuring phospholipase D activities. [Doctoral Dissertation]. Lyon; 2016. Available from: http://www.theses.fr/2016LYSE1292

23. Bourtsala, Angeliki. Μελέτη της δράσης φωσφολιπασών D κατά την απόκριση του φυτού Gossypium hirsutum σε περιβαλλοντικές καταπονήσεις.

Degree: 2017, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/46946

►

Phospholipases D (PLD, E.C. 3.1.4.4) hydrolyze membrane phospholipids and are present in allorganisms studied. Plant PLDs exist in a wide range of isoforms, classified into… (more)

▼

Phospholipases D (PLD, E.C. 3.1.4.4) hydrolyze membrane phospholipids and are present in allorganisms studied. Plant PLDs exist in a wide range of isoforms, classified into six classes (α-ζ). Among them, α and δ are the most common. PLD activity in plants is involved in environmental stress responses via its product, phosphatidic acid (PtdOH), a signalling molecule. In the presence of aprimary alcohol, PLD hydrolytic activity is partially inhibited, as PLD transphosphatidylation reaction is preferentially catalyzed. In this study, we have found for the first time PLD activity in microsomal fraction of cultivated cotton (Gossypium hirsutum). Upon mechanical wounding -resembling tissue damage caused by biotic orabiotic factors- acute increase of PLDα isoform activity was observed in leaves, both locally and systemically. Endogenous PtdOH determination revealed analogous, rapid increase of its concentration locally, while duplication in PtdOH levels was observed as a late, local and systemic, response to wounding. Moreover, it was found that phosphatidylethanolamine is the prefered PLDα substrate and itis also preferentially consumed during early stages after wounding. However, after 30 min, a shift inselectivity towards phosphatidylcholine was observed, possibly due to other PLD isoforms’ activity, mainly δ. Expression analysis of PLDα and δ isoforms showed mRNA accumulation of both isoforms in the wounded tissue, but only PLDδ was induced in systemic leaves, suggesting that PLDδ is mainly responsible for systemic response to wounding. This was confirmed by PLDδ activity assay. Finally, expression experiments showed that lipoxygenase, NADPH oxidase and cellulose synthase arewound-induced, as well. In vivo effect of 1-butanol, that suppresses PLD-derived PtdOH production, inhibits the induction of all three genes tested, implying that they are possible downstream PLD targets during G. hirsutum stress.

Οι φωσφολιπάσες D (PLD, E.C. 3.1.4.4) είναι υδρολυτικά ένζυμα που δρουν σε φωσφολιπίδια των μεμβρανών και απαντώνται σε όλους τους οργανισμούς. Οι φυτικές PLD εμφανίζουν τη μεγαλύτερη ποικιλία ισομορφών, που κατατάσσονται σε έξι τάξεις (α-ζ). Από αυτές, οι α και δ είναι οι πιο διαδεδομένες. Η δράση των PLD στα φυτά συνδέεται με αποκρίσεις σε περιβαλλοντικές καταπονήσεις μέσω του παραγόμενου φωσφατιδικού οξέος (PtdOH), που δρα ως ενδοκυτταρικό σήμα. Στην περίπτωση παρουσίας πρωτοταγούς αλκοόλης, αναστέλλεται μερικώς η υδρολυτική δράση των PLDκαι καταλύεται η χαρακτηριστική για το ένζυμο αντίδραση μεταφωσφατιδυλίωσης. Στο καλλιεργούμενο βαμβάκι (Gossypium hirsutum) εντοπίστηκε για πρώτη φορά δραστικότητα PLDστο κλάσμα των μικροσωμάτων. Μετά από μηχανικό τραυματισμό -που προσομοιάζει με βλάβη στον ιστό προερχόμενη είτε από βιοτικούς είτε από αβιοτικούς παράγοντες- παρατηρήθηκε άμεση αύξηση της δραστικότητας της ισομορφής α της PLD στα φύλλα, τοπικά και συστημικά. Ο προσδιορισμός των ενδογενών επιπέδων PtdOH αποκάλυψε ανάλογη, ραγδαία αύξηση της συγκέντρωσης του λιπιδίου τοπικά, ενώ διπλασιασμός των επιπέδων του…

Subjects/Keywords: Φωσφολιπάση D; Φωσφατιδικό οξύ; Καλλιεργούμενο βαμβάκι; Τραυματισμός; Phospholipase D; PLDα; PLDδ; Phosphatidic acid; Cultivated cotton; G. hirsutum; Wounding

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bourtsala, A. (2017). Μελέτη της δράσης φωσφολιπασών D κατά την απόκριση του φυτού Gossypium hirsutum σε περιβαλλοντικές καταπονήσεις. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/46946

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bourtsala, Angeliki. “Μελέτη της δράσης φωσφολιπασών D κατά την απόκριση του φυτού Gossypium hirsutum σε περιβαλλοντικές καταπονήσεις.” 2017. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed January 20, 2021. http://hdl.handle.net/10442/hedi/46946.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bourtsala, Angeliki. “Μελέτη της δράσης φωσφολιπασών D κατά την απόκριση του φυτού Gossypium hirsutum σε περιβαλλοντικές καταπονήσεις.” 2017. Web. 20 Jan 2021.

Vancouver:

Bourtsala A. Μελέτη της δράσης φωσφολιπασών D κατά την απόκριση του φυτού Gossypium hirsutum σε περιβαλλοντικές καταπονήσεις. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/10442/hedi/46946.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bourtsala A. Μελέτη της δράσης φωσφολιπασών D κατά την απόκριση του φυτού Gossypium hirsutum σε περιβαλλοντικές καταπονήσεις. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2017. Available from: http://hdl.handle.net/10442/hedi/46946

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Gothenburg / Göteborgs Universitet

24. Asp, Lennart 1965-. Effects of ARF1 and phospholipase D on the assembly and secretion of apoB-100 containing lipoproteins.

Degree: 2002, University of Gothenburg / Göteborgs Universitet

URL: http://hdl.handle.net/2077/15514

► Hydrophobic insoluble lipids such as triglycerides and cholesterol ester are transported in spherical, water-soluble molecular complexes called lipoproteins. Lipoproteins are secreted mainly from the liver… (more)

▼ Hydrophobic insoluble lipids such as triglycerides and cholesterol ester are transported in spherical, water-soluble molecular complexes called lipoproteins. Lipoproteins are secreted mainly from the liver and intestine into the plasma for distribution to peripheral tissues. In this thesis, the assembly and secretion of one form of these lipoproteins have been studied: very low density lipoproteins (VLDL). Apolipoprotein (apo) B-100 is the major structural protein of VLDL and is essential for assembly of the particle. The assembly of VLDL has been suggested to involve two relatively well-defined steps. In the first step, apoB-100 is co-translationally translocated through the ER membrane forming pre-VLDL with a density corresponding to high density lipoproteins (HDL) or low density lipoproteins (LDL). The second step is thought to include the formation of a apoB- free lipid droplets in the ER lumen, which are fused en bloc with pre-VLDL forming VLDL. The results presented show that apoB-100 is sorted to degradation at different levels in the secretory pathway. Thus, membrane-associated apoB-100 was degraded via an ATP-dependent pathway, most likely corresponding to the recently discovered proteasomal pathway. ApoB-100 present on HDL and LDL particles in the secretory pathway was degraded by an ALLN-sensitive degradation pathway. The GTP-binding protein ADP ribosylation factor 1 (ARF1) inhibited the non-proteasomal degradation of apoB-100. ARF1 was also essential for the second step in the assembly of apoB-100 VLDL, giving a molecular explanation for the inhibitory effect of brefeldin A on the process. Phospholipase D (PLD) activity stimulated the assembly of apoB-100 VLDL in a cell-free system reconstituting the assembly process. Moreover, the results indicate that ARF1 mediates its effect on the assembly of VLDL by activating PLD. The activity of PLD was also essential for the formation of small cytosolic lipid droplets in a cell-free system. Thus, the dependence on PLD for both of these processes may suggest a common mechanism for the formation of small lipid droplets, either they are sorted to the cytosol or sorted to the ER lumen and secreted as VLDL.

Subjects/Keywords: ApoB; ARF1; Phospholipase D; Lipoproteins; VLDL;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Asp, L. 1. (2002). Effects of ARF1 and phospholipase D on the assembly and secretion of apoB-100 containing lipoproteins. (Thesis). University of Gothenburg / Göteborgs Universitet. Retrieved from http://hdl.handle.net/2077/15514

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Asp, Lennart 1965-. “Effects of ARF1 and phospholipase D on the assembly and secretion of apoB-100 containing lipoproteins.” 2002. Thesis, University of Gothenburg / Göteborgs Universitet. Accessed January 20, 2021. http://hdl.handle.net/2077/15514.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Asp, Lennart 1965-. “Effects of ARF1 and phospholipase D on the assembly and secretion of apoB-100 containing lipoproteins.” 2002. Web. 20 Jan 2021.

Vancouver:

Asp L1. Effects of ARF1 and phospholipase D on the assembly and secretion of apoB-100 containing lipoproteins. [Internet] [Thesis]. University of Gothenburg / Göteborgs Universitet; 2002. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2077/15514.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Asp L1. Effects of ARF1 and phospholipase D on the assembly and secretion of apoB-100 containing lipoproteins. [Thesis]. University of Gothenburg / Göteborgs Universitet; 2002. Available from: http://hdl.handle.net/2077/15514

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

25. SWAMINATHAN SETHU. Role of PLD and SPHK in TNFa induced signaling and inflammatory responses.

Degree: 2009, National University of Singapore

URL: http://scholarbank.nus.edu.sg/handle/10635/16400

Subjects/Keywords: Inflammation; TNFa; Phospholipase D; Sphingosine kinase; intracellular signaling; Peritonitis.

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

SETHU, S. (2009). Role of PLD and SPHK in TNFa induced signaling and inflammatory responses. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/16400

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

SETHU, SWAMINATHAN. “Role of PLD and SPHK in TNFa induced signaling and inflammatory responses.” 2009. Thesis, National University of Singapore. Accessed January 20, 2021. http://scholarbank.nus.edu.sg/handle/10635/16400.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

SETHU, SWAMINATHAN. “Role of PLD and SPHK in TNFa induced signaling and inflammatory responses.” 2009. Web. 20 Jan 2021.

Vancouver:

SETHU S. Role of PLD and SPHK in TNFa induced signaling and inflammatory responses. [Internet] [Thesis]. National University of Singapore; 2009. [cited 2021 Jan 20]. Available from: http://scholarbank.nus.edu.sg/handle/10635/16400.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

SETHU S. Role of PLD and SPHK in TNFa induced signaling and inflammatory responses. [Thesis]. National University of Singapore; 2009. Available from: http://scholarbank.nus.edu.sg/handle/10635/16400

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

East Tennessee State University

26. Swati, Swati. Cloning of N-acylethanolamine Metabolic Pathway Genes from Physcomitrella patens.

Degree: MS, Biology, 2017, East Tennessee State University

URL: https://dc.etsu.edu/etd/3178

► N-acylethanolamines (NAEs) including anandamide are lipid derivative molecules, which play vital roles in physiological and developmental processes in plants and animals and mediate stress… (more)

Subjects/Keywords: Anandamide; Fatty Acid Amide Hydrolase; N-acylethanolamine; N-acylphosphatidylethanolamine; N-acylphosphatidylethanolamine-Phospholipase D; N-acylphosphatidylethanolamine; Physcomitrella patens; Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Swati, S. (2017). Cloning of N-acylethanolamine Metabolic Pathway Genes from Physcomitrella patens. (Thesis). East Tennessee State University. Retrieved from https://dc.etsu.edu/etd/3178

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Swati, Swati. “Cloning of N-acylethanolamine Metabolic Pathway Genes from Physcomitrella patens.” 2017. Thesis, East Tennessee State University. Accessed January 20, 2021. https://dc.etsu.edu/etd/3178.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Swati, Swati. “Cloning of N-acylethanolamine Metabolic Pathway Genes from Physcomitrella patens.” 2017. Web. 20 Jan 2021.

Vancouver:

Swati S. Cloning of N-acylethanolamine Metabolic Pathway Genes from Physcomitrella patens. [Internet] [Thesis]. East Tennessee State University; 2017. [cited 2021 Jan 20]. Available from: https://dc.etsu.edu/etd/3178.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Swati S. Cloning of N-acylethanolamine Metabolic Pathway Genes from Physcomitrella patens. [Thesis]. East Tennessee State University; 2017. Available from: https://dc.etsu.edu/etd/3178

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

27. Rosenberger, Christina Laura. Regulation of mTORC1 by phosphatidic acid: mechanism and structural insight.

Degree: PhD, Cell and Developmental Biology, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/92925

► The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase with remarkable control over cellular status. As a master regulator, mTOR integrates a variety of… (more)

▼ The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase with remarkable control over cellular status. As a master regulator, mTOR integrates a variety of intra- and extra-cellular signals in order to coordinate them with appropriate gene expression, protein synthesis, metabolism, cell migration, autophagy – the list goes on! mTOR signaling, with involvement in so many important cellular processes, can have detrimental physiological effects when dysregulated. Aberrant mTOR signaling is now known to contribute to a great number of the major pathologies we face today. Understanding how mTOR is normally regulated is, therefore, important for informing the development of effective and specific therapeutics for diseases like cancer and diabetes. Significant research efforts over the last two decades have informed our current understanding of the extensive mTOR signaling pathways, but many questions remain. In my dissertation work I have investigated longstanding mysteries of mTOR activation by mitogens and nutrients, with specific focus on the mechanism by which the lipid second messenger, phosphatidic acid, activates mTOR complex 1. The mammalian target of rapamycin complex 1 (mTORC1) is regulated, in part, by the endogenous inhibitor DEPTOR. However, the mechanism of DEPTOR regulation with regard to rapid mTORC1 activation remains unknown. In collaboration with Dr. Mee Sup Yoon, I discovered that DEPTOR is rapidly and temporarily dissociated from mTORC1 upon mitogenic stimulation. We demonstrated that this mitogen stimulated DEPTOR dissociation is blocked by inhibition or depletion of the mTORC1 regulator, phospholipase D (PLD), and is recapitulated with the addition of the PLD product phosphatidic acid (PA). Parallel mass spectrometry analysis independently identified DEPTOR as an mTOR binding partner dissociated by PA. Interestingly, I found that only PA species with unsaturated fatty acid chains, such as those produced by PLD, are capable of displacing DEPTOR and activating mTORC1, with high affinity for the FRB domain of mTOR. Our findings, detailed in Chapter II reveal a mechanism of acute mTORC1 regulation that was previously unidentified and provide a molecular explanation for the exquisite specificity of PA function. In light of PA’s essential role in mTORC1 activation, I found it striking that mTOR proteins containing one of several point mutations have been reported to remain catalytically active in conditions when amino acids, and therefore PA, are absent. The existence of such hyperactive mTOR prompted me to ask whether a point mutation can render mTOR independent of regulation by PA and, if so, by what mechanism? In Chapter III, I describe how by examining the activity of several mTOR proteins each carrying a unique point mutation known to be associated with human cancer, I discovered that individual point mutations can confer varying degrees of PA-independent mTORC1 activity. My finding that an L1460P mutation in mTOR's FAT domain, S2215Y mutation in the kinase N-lobe, and E2419K in the kinase… Advisors/Committee Members: Chen, Jie (advisor), Chen, Jie (Committee Chair), Belmont, Andrew (committee member), Chen, Lin-Feng (committee member), Rivier, David (committee member).

Subjects/Keywords: Mammalian target of rapamycin (mTOR); phosphatidic acid; phospholipase D (PLD); DEP Domain Containing MTOR-Interacting Protein (DEPTOR); hyperactive; cancer

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rosenberger, C. L. (2016). Regulation of mTORC1 by phosphatidic acid: mechanism and structural insight. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/92925

Chicago Manual of Style (16^th Edition):

Rosenberger, Christina Laura. “Regulation of mTORC1 by phosphatidic acid: mechanism and structural insight.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed January 20, 2021. http://hdl.handle.net/2142/92925.

MLA Handbook (7^th Edition):

Rosenberger, Christina Laura. “Regulation of mTORC1 by phosphatidic acid: mechanism and structural insight.” 2016. Web. 20 Jan 2021.

Vancouver:

Rosenberger CL. Regulation of mTORC1 by phosphatidic acid: mechanism and structural insight. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/2142/92925.

Council of Science Editors:

Rosenberger CL. Regulation of mTORC1 by phosphatidic acid: mechanism and structural insight. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/92925

University of Edinburgh

28. Barclay, Zoë Jade. Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant.

Degree: PhD, 2010, University of Edinburgh

URL: http://hdl.handle.net/1842/4483

► The 5-HT2A receptor (5-HT2AR) is implicated in neuropsychiatric disorders such as schizophrenia and is thought to mediate the actions of a number of hallucinogenic and… (more)

▼ The 5-HT2A receptor (5-HT2AR) is implicated in neuropsychiatric disorders such as schizophrenia and is thought to mediate the actions of a number of hallucinogenic and antipsychotic drugs. Additionally, certain polymorphic variants of the receptor, such as an allele resulting in substitution of amino acid 452 histidine (H) with tyrosine (Y), have been linked to schizophrenia or altered therapeutic response to antipsychotics. The 5-HT2AR utilises various intracellular signalling pathways, including the activation of phospholipase C (PLC) and phospholipase D (PLD) via recruitment of the small G-protein ADP-Ribosylation Factor (ARF). This thesis focusses on protein:protein interactions and signalling mechanisms of the 5-HT2AR and H452Y-5-HT2AR receptor variant. Both ARF1 and PLD1 have previously been shown to bind to the carboxy-terminal tail (ct) of the 5-HT2AR. In chapter three it is demonstrated that the 5-HT2AR can activate PLD in an ARF-dependent manner, primarily through the PLD1 isoform. GST-fusion proteins of truncated and mutated variants of the receptor ct are used to show that ARF1 and PLD1 independently bind to distinct sites. Coimmunoprecipitation, GST-fusion protein studies and PLD activity assays demonstrate that the introduction of the H452Y mutation decreases the physical interactions between the receptor and PLD1, as well as decreasing 5-HT2ARmediated PLD activation. In chapter four, potential mechanisms of wild-type and H452Y-5-HT2AR desensitisation are explored. It is shown that β-arrestin 2 (β-arr 2) confers a decrease in H452Y-5-HT2AR-mediated PLC activity, despite having no significant effect upon wild-type 5-HT2AR responses. The H452Y-5-HT2AR variant is also shown, by GST-fusion protein studies, to bind β-arr 2 more strongly. The H452Y-5-HT2AR additionally mediates increased levels of 5-HT-induced ERK phosphorylation compared to the wild type 5-HT2AR, potentially through increased scaffolding of ERK activation complexes by receptor-bound β-arr 2. Chapter five focusses on possible interactions of the 5-HT2AR with the Ca2+-binding proteins annexin A2, S100B and the annexin A2 partner p11, together with the functional consequences of these interactions. Co-immunoprecipiation and GST-fusion protein studies show that annexin A2 binds specifically to the 5-HT2AR ct. Furthermore, annexin A2 (but not S100B or p11) is shown to result in an amplification of 5-HT2AR-mediated PLC responses. These findings provide a greater insight into some of the signal transduction mechanisms of the 5-HT2AR and their perturbation in the H452Y polymorphic form of the receptor, and understanding of the molecular mechanisms underlying neuropsychiatric diseases in patient subgroups, potentially leading to improved therapeutic treatments.

Subjects/Keywords: 615.1; 5-HT2AR receptor; PLD; phospholipase D; H452Y

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Barclay, Z. J. (2010). Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/4483

Chicago Manual of Style (16^th Edition):

Barclay, Zoë Jade. “Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant.” 2010. Doctoral Dissertation, University of Edinburgh. Accessed January 20, 2021. http://hdl.handle.net/1842/4483.

MLA Handbook (7^th Edition):

Barclay, Zoë Jade. “Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant.” 2010. Web. 20 Jan 2021.

Vancouver:

Barclay ZJ. Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant. [Internet] [Doctoral dissertation]. University of Edinburgh; 2010. [cited 2021 Jan 20]. Available from: http://hdl.handle.net/1842/4483.

Council of Science Editors:

Barclay ZJ. Signal transduction by the 5-HT2A receptor and its H452Y polymorphic variant. [Doctoral Dissertation]. University of Edinburgh; 2010. Available from: http://hdl.handle.net/1842/4483

University of Guelph

29. DeBrouwer, Erika J. Improvement of the Shelf Life in ‘Honeycrisp’ Apples (Malus domestica Borkh.) using Hexanal.

Degree: MS, Department of Plant Agriculture, 2019, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17682

► In this study the effects of hexanal, a potential postharvest preservative, contained within ‘Enhanced Freshness Formulation’ (EFF), on apple ripening was investigated. EFF was sprayed… (more)

Subjects/Keywords: Honeycrisp; hexanal; EFF; Bitter Pit; calcium; SEM; Enhanced Freshness Formulation; apple; PLD; Phospholipase-D; postharvest; storage; shelf life; post harvest

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

DeBrouwer, E. J. (2019). Improvement of the Shelf Life in ‘Honeycrisp’ Apples (Malus domestica Borkh.) using Hexanal. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17682

Chicago Manual of Style (16^th Edition):

DeBrouwer, Erika J. “Improvement of the Shelf Life in ‘Honeycrisp’ Apples (Malus domestica Borkh.) using Hexanal.” 2019. Masters Thesis, University of Guelph. Accessed January 20, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17682.

MLA Handbook (7^th Edition):

DeBrouwer, Erika J. “Improvement of the Shelf Life in ‘Honeycrisp’ Apples (Malus domestica Borkh.) using Hexanal.” 2019. Web. 20 Jan 2021.

Vancouver:

DeBrouwer EJ. Improvement of the Shelf Life in ‘Honeycrisp’ Apples (Malus domestica Borkh.) using Hexanal. [Internet] [Masters thesis]. University of Guelph; 2019. [cited 2021 Jan 20]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17682.

Council of Science Editors:

DeBrouwer EJ. Improvement of the Shelf Life in ‘Honeycrisp’ Apples (Malus domestica Borkh.) using Hexanal. [Masters Thesis]. University of Guelph; 2019. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/17682

Wright State University

30. Fite, Kristen. Dysregulation of Phospholipase D (PLD) isoforms increases breast cancer cell invasion.

Degree: PhD, Biomedical Sciences PhD, 2017, Wright State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright149557402792618

► Breast cancer remains the second most prevalent cancer among women in the U.S. with metastatic breast cancer having the worst prognosis. A rapidly proliferating tumor… (more)

▼ Breast cancer remains the second most prevalent cancer among women in the U.S. with metastatic breast cancer having the worst prognosis. A rapidly proliferating tumor under various stressors will promote phenotypic cellular changes, known as epithelial-to-mesenchymal transition (EMT), which allows cells to begin to invade surrounding tissue, enter the circulatory system, and eventually seed a distant metastatic site. The phospholipase D (PLD) enzymes are critical regulators of cell signaling pathways necessary for cell migration. While the importance of PLD enzymes in cancer cell invasion is well known, clinically applicable methods of PLD inhibition are not yet available. The best-studied isoforms are the `classical’ PLD1 and PLD2 membrane lipases that hydrolyze phosphatidylcholine (PC) to free choline and phosphatidic acid (PA). PA acts as a secondary messenger activating numerous pathways leading to cell growth and proliferation, vesicle trafficking, and cell migration. PLD1 and PLD2 are upregulated in several cancers including breast and, furthermore, promote tumorigenesis and disease progression. However, the specific molecular mechanism that regulates overexpression of PLD1 and PLD2 in cancer remains unclear. I investigated post-transcriptional regulation of the classical PLD isoforms by microRNA (miRNA) in cancer cell invasion and in stress (nutrient starvation) leading to EMT. MicroRNA are currently widely investigated as potential therapeutic agents involved in a myriad of diseases. Naturally produced in the body, miRNA are attractive therapeutic molecules based on their small size, surprising stability, and potent regulatory capabilities. A repertoire of four microRNAs present in non-cancerous breast cells that are down-regulated in invasive breast cancer cell were found and demonstration of their regulation of PLD1 or PLD2 mRNA was done by luciferase reporter assay. Exogenous addition of these microRNAs to invasive breast cancer cells reduced cell invasion. Additionally, initial nutrient starvation increased classical PLD protein levels, concomitant with cell invasion. With prolonged starvation, PLD-targeting microRNA were upregulated and functioned in a negative feedback loop to downregulate PLD protein expression. While much is known about the PLD1 and PLD2 isoforms, the other mammalian PLD isoforms (PLD3, PLD4, and PLD6) are vastly less studied. Interestingly, PLD6 has recently been found to be overexpressed in breast cancer tumors, however, further studies investigating the role of PLD6 in cancer progression have not been published. PLD6 localizes to the mitochondrial outer membrane and uses cardiolipin as a substrate to produce PA. This reaction promotes mitochondrial fusion, thereby inhibiting apoptosis, while increasing oxidative phosphorylation, both of which are critical to cancer progression. While PLD1 and PLD2 are ubiquitously expressed, PLD6 is expressed at lower basal levels in most tissues, making PLD6 an attractive therapeutic target, when upregulated in cancer, with potentially less… Advisors/Committee Members: Gomez-Cambronero, Julian (Advisor).

Subjects/Keywords: Biomedical Research; Biochemistry; Cellular Biology; Biomedical science; cell signaling; biochemistry; breast cancer; cell invasion; phospholipase D; microRNA

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APA (6^th Edition):

Fite, K. (2017). Dysregulation of Phospholipase D (PLD) isoforms increases breast cancer cell invasion. (Doctoral Dissertation). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright149557402792618

Chicago Manual of Style (16^th Edition):

Fite, Kristen. “Dysregulation of Phospholipase D (PLD) isoforms increases breast cancer cell invasion.” 2017. Doctoral Dissertation, Wright State University. Accessed January 20, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright149557402792618.

MLA Handbook (7^th Edition):

Fite, Kristen. “Dysregulation of Phospholipase D (PLD) isoforms increases breast cancer cell invasion.” 2017. Web. 20 Jan 2021.

Vancouver:

Fite K. Dysregulation of Phospholipase D (PLD) isoforms increases breast cancer cell invasion. [Internet] [Doctoral dissertation]. Wright State University; 2017. [cited 2021 Jan 20]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright149557402792618.

Council of Science Editors:

Fite K. Dysregulation of Phospholipase D (PLD) isoforms increases breast cancer cell invasion. [Doctoral Dissertation]. Wright State University; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright149557402792618

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