subject:(Phosphatidic acids)

1. 山本, 梓司. Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果.

Degree: 博士(医学), 2018, Saitama Medical University / 埼玉医科大学

URL: http://id.nii.ac.jp/1386/00000615/

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Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination,… (more)

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Multiple sclerosis is a neuroinflammatory demyelinating and neurodegenerative disease of the central nervous system characterized by recurrent and progressive demyelination/remyelination cycles, neuroinflammation, oligodendrocyte loss, demyelination, and axonal degeneration. Cyclic phosphatidic acid (cPA) is a natural phospholipid mediator with a unique cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. We reported earlier that cPA elicits a neurotrophin-like action and protects hippocampal neurons from ischemia-induced delayed neuronal death. We designed, chemically synthesized, and metabolically stabilized derivatives of cPA: 2-carba-cPA (2ccPA), a synthesized compound in which one of the phosphate oxygen molecules is replaced with a methylene group at the sn-2 position. In the present study, we investigated whether 2ccPA exerts protective effects in oligodendrocytes and suppresses pathology in the two most common mouse models of multiple sclerosis.

To evaluate whether 2ccPA has potential beneficial effects on the pathology of multiple sclerosis, we investigated the effects of 2ccPA on oligodendrocyte cell death in vitro and administrated 2ccPA to mouse models of experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination.

We demonstrated that 2ccPA suppressed the CoCl

-induced increase in the Bax/Bcl-2 protein expression ratio and phosphorylation levels of p38MAPK and JNK protein. 2ccPA treatment reduced cuprizone-induced demyelination, microglial activation, NLRP3 inflammasome, and motor dysfunction. Furthermore, 2ccPA treatment reduced autoreactive T cells and macrophages, spinal cord injury, and pathological scores in EAE, the autoimmune multiple sclerosis mouse model.

We demonstrated that 2ccPA protected oligodendrocytes via suppression of the mitochondrial apoptosis pathway. Also, we found beneficial effects of 2ccPA in the multiperiod of cuprizone-induced demyelination and the pathology of EAE. These data indicate that 2ccPA may be a promising compound for the development of new drugs to treat demyelinating disease and ameliorate the symptoms of multiple sclerosis.

平成29年度

Subjects/Keywords: Animals; Anti-Inflammatory Agents; Apoptosis; Cell Differentiation; Cell Line, Transformed; Cuprizone; Demyelinating Diseases; Disease Models, Animal; Female; Gene Expression Regulation; Humans; MAP Kinase Signaling System; Male; Mice; Mice, Inbred C57BL; Monoamine Oxidase Inhibitors; Myelin Sheath; NLR Family, Pyrin Domain-Containing 3 Protein; Phosphatidic Acids; Proto-Oncogene Proteins c-bcl-2; p38 Mitogen-Activated Protein Kinases

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

APA (6^th Edition):

山本, �. (2018). Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果. (Thesis). Saitama Medical University / 埼玉医科大学. Retrieved from http://id.nii.ac.jp/1386/00000615/

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):

山本, 梓司. “Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果.” 2018. Thesis, Saitama Medical University / 埼玉医科大学. Accessed March 07, 2021. http://id.nii.ac.jp/1386/00000615/.

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

MLA Handbook (7^th Edition):

山本, 梓司. “Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果.” 2018. Web. 07 Mar 2021.

Vancouver:

山本 �. Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果. [Internet] [Thesis]. Saitama Medical University / 埼玉医科大学; 2018. [cited 2021 Mar 07]. Available from: http://id.nii.ac.jp/1386/00000615/.

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

Council of Science Editors:

山本 �. Protective and therapeutic role of 2-carba-cyclic phosphatidic acid in demyelinating disease. : 脱髄性疾患における環状ホスファチジン酸誘導体の脱髄抑制及び治療効果. [Thesis]. Saitama Medical University / 埼玉医科大学; 2018. Available from: http://id.nii.ac.jp/1386/00000615/

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

Michigan State University

2. Lu, Binbin. Functional analysis of a phosphatidic acid transport system in Arabidopsis thaliana.

Degree: PhD, Department of Biochemistry and Molecular Biology, 2009, Michigan State University

URL: http://etd.lib.msu.edu/islandora/object/etd:17024

Subjects/Keywords: Phosphatidic acids – Physiological transport; Arabidopsis thaliana – Physiology

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

APA (6^th Edition):

Lu, B. (2009). Functional analysis of a phosphatidic acid transport system in Arabidopsis thaliana. (Doctoral Dissertation). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:17024

Chicago Manual of Style (16^th Edition):

Lu, Binbin. “Functional analysis of a phosphatidic acid transport system in Arabidopsis thaliana.” 2009. Doctoral Dissertation, Michigan State University. Accessed March 07, 2021. http://etd.lib.msu.edu/islandora/object/etd:17024.

MLA Handbook (7^th Edition):

Lu, Binbin. “Functional analysis of a phosphatidic acid transport system in Arabidopsis thaliana.” 2009. Web. 07 Mar 2021.

Vancouver:

Lu B. Functional analysis of a phosphatidic acid transport system in Arabidopsis thaliana. [Internet] [Doctoral dissertation]. Michigan State University; 2009. [cited 2021 Mar 07]. Available from: http://etd.lib.msu.edu/islandora/object/etd:17024.

Council of Science Editors:

Lu B. Functional analysis of a phosphatidic acid transport system in Arabidopsis thaliana. [Doctoral Dissertation]. Michigan State University; 2009. Available from: http://etd.lib.msu.edu/islandora/object/etd:17024

3. Tsukahara, Ryoko. Characterization of the Mechanism of PPARγ-Mediated Neointima Formation in Rodents.

Degree: PhD, Biomedical Sciences, 2011, University of Tennessee Health Science Center

URL: https://dc.uthsc.edu/dissertations/270

► Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is… (more)

▼ Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor γ (PPARγ). We pursued a gene knockout strategy to identify the LPA receptor subtypes necessary for the neointimal response in a non-injury model of carotid remodeling and also compared the effects of AGP and the PPARγ agonist rosiglitazone (ROSI) on balloon injury-elicited neointima development. In the balloon injury model AGP significantly increased neointima; however, rosiglitazone application attenuated it. AGP and ROSI were also applied intralumenally for 1 hour without injury into the carotid arteries of LPA1, LPA2, LPA1&2 double knockout, and Mx1Cre-inducible conditional PPARγ knockout mice targeted to vascular smooth muscle cells, macrophages, and endothelial cells. The neointima was quantified and also stained for CD31, CD68, CD11b, and "-smooth muscle actin markers. In LPA1, LPA2, LPA1&2 GPCR knockouts, Mx1Cre transgenic, PPARγ fl/- , and uninduced Mx1Cre#PPAR! fl/- mice AGP- and ROSI-elicited neointima was indistinguishable in its progression and cytological features from that of WT C57BL/6 mice. In PPARγ -/- knockout mice, generated by activation of Mx1Cre-mediated recombination, AGP and ROSI failed to elicit neointima and vascular wall remodeling. Our findings point to a difference in the effects of AGP and ROSI between the balloon-injury- and the non-injury chemically-induced neointima. The present data provide genetic evidence for the requirement of PPARγ in AGP- and ROSI-elicited neointimal thickening in the non-injury model and reveal that the overwhelming majority of the cells in the neointimal layer express !-smooth muscle actin. Cyclic phosphatidic acid (1-acyl-2,3-cyclic-glycerophosphate, CPA), one of nature’s simplest phospholipids, is found in cells from slime mold to humans and has largely unknown function. We find that CPA is generated in mammalian cells in a stimulus coupled-manner by phospholipase D2 (PLD2), and binds to and inhibits the nuclear hormone receptor PPAR! with nanomolar affinity and high specificity through stabilizing its interaction with the corepressor SMRT. CPA production inhibits the PPAR! target-gene transcription that normally drives adipocytic differentiation of 3T3-L1 cells, lipid accumulation in RAW264.7 cells and primary mouse macrophages, and arterial wall remodeling in vivo. Inhibition of PLD2 by shRNA, a dominant negative mutant, or a small molecule inhibitor blocks CPA production and relieves PPARγ inhibition. We conclude that CPA is a novel second messenger and a physiological inhibitor of PPARγ, revealing that PPARγ is regulated by endogenous agonists as well as by antagonists. PPAR" is a nuclear hormone receptor related to many human diseases, including obesity, atherosclerosis, diabetes, and cancers. Recent studies have provided evidence that LPA and its analog AGP activate PPARγ. On the… Advisors/Committee Members: Gabor J. Tigyi, M.D., Ph.D..

Subjects/Keywords: lysophosphatidic acid; cyclic phosphatidic acid; phospholipase D; neointima; atherosclerosis; PPAR!; Amino Acids, Peptides, and Proteins; Cardiovascular Diseases; Chemicals and Drugs; Diseases; Lipids; Medical Sciences; Medicine and Health Sciences

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

APA (6^th Edition):

Tsukahara, R. (2011). Characterization of the Mechanism of PPARγ-Mediated Neointima Formation in Rodents. (Doctoral Dissertation). University of Tennessee Health Science Center. Retrieved from https://dc.uthsc.edu/dissertations/270

Chicago Manual of Style (16^th Edition):

Tsukahara, Ryoko. “Characterization of the Mechanism of PPARγ-Mediated Neointima Formation in Rodents.” 2011. Doctoral Dissertation, University of Tennessee Health Science Center. Accessed March 07, 2021. https://dc.uthsc.edu/dissertations/270.

MLA Handbook (7^th Edition):

Tsukahara, Ryoko. “Characterization of the Mechanism of PPARγ-Mediated Neointima Formation in Rodents.” 2011. Web. 07 Mar 2021.

Vancouver:

Tsukahara R. Characterization of the Mechanism of PPARγ-Mediated Neointima Formation in Rodents. [Internet] [Doctoral dissertation]. University of Tennessee Health Science Center; 2011. [cited 2021 Mar 07]. Available from: https://dc.uthsc.edu/dissertations/270.

Council of Science Editors:

Tsukahara R. Characterization of the Mechanism of PPARγ-Mediated Neointima Formation in Rodents. [Doctoral Dissertation]. University of Tennessee Health Science Center; 2011. Available from: https://dc.uthsc.edu/dissertations/270

Georgia Tech

4. Urs, Aarti N. Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17.

Degree: MS, Biology, 2005, Georgia Tech

URL: http://hdl.handle.net/1853/7638

► Steroidogenic factor (SF1) is an orphan nuclear receptor that is essential for steroid hormone-biosynthesis and endocrine development. Recent studies have demonstrated that phospholipids are ligands… (more)

Subjects/Keywords: CYP17; Sphingosine; Phosphatidic acids; Steroidogenic factor 1; Transcription factors; Steroid hormones Synthesis; Sphingosine; Pregnenolone; Phospholipids; Ligands

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Urs, A. N. (2005). Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7638

Chicago Manual of Style (16^th Edition):

Urs, Aarti N. “Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17.” 2005. Masters Thesis, Georgia Tech. Accessed March 07, 2021. http://hdl.handle.net/1853/7638.

MLA Handbook (7^th Edition):

Urs, Aarti N. “Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17.” 2005. Web. 07 Mar 2021.

Vancouver:

Urs AN. Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17. [Internet] [Masters thesis]. Georgia Tech; 2005. [cited 2021 Mar 07]. Available from: http://hdl.handle.net/1853/7638.

Council of Science Editors:

Urs AN. Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17. [Masters Thesis]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7638

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