+publisher:"University of Kansas" +contributor:("Staudinger, Jeff L.")

University of Kansas

1. Chen, Yao. Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes.

Degree: PhD, Pharmaceutical Chemistry, 2016, University of Kansas

► Quantification of highly homologous human liver drug-metabolizing enzymes (DMEs) has been a challenging task in drug metabolism and disposition research, due to a lack of… (more)

▼ Quantification of highly homologous human liver drug-metabolizing enzymes (DMEs) has been a challenging task in drug metabolism and disposition research, due to a lack of specific antibodies and marker substrates. Mass spectrometry (MS) techniques and applications have evolved significantly, striving to achieve absolute and specific quantification of these enzymes. Since the first absolute quantification of cytochrome P450s (CYPs) using the attachment of isotope tags to free thiols (iCAT), MS-based quantification has become much more versatile, cheaper, and easier to use. Today, variations of liquid chromatography-multiple reaction monitoring (LC-MRM)-based targeted proteomics, such as AQUA (absolute quantification) and QconCAT (concatenated signature peptides), have become the gold standards for quantification. These new methods have driven the absolute quantification of DMEs to become a routine laboratory task. Many drug metabolism-related projects require absolute enzyme quantification. For example, precise knowledge of enzyme expression during ontogeny is a necessity to aid pharmacists in planning drug-dosing regimens for patients of different age groups. Additional examples include the need for accurate cellular enzyme expression profiles when establishing new drug-screening cell models and when elucidating molecular mechanisms underlying hypothesized drug-drug interactions. This dissertation demonstrates how an LC-MRM targeted approach contributes to these three areas. First, an ultra-performance liquid chromatography (UPLC)-MRM targeted quantification method was developed and validated, focusing specifically on the quantification of CYP2C and flavin-containing monoxoygenase (FMO) isoforms. Second, the newly developed, as well as existing, UPLC-MRM quantification methods were used to confirm previously reported DME ontogeny patterns and establish patterns for CYP4F and FMO5. Third, targeted proteomic quantification was employed for the absolute quantification of CYPs 1A1, 1A2 and 1B1 in KLE cells and different human tissue microsomes to aid the establishment of CYP1B1-dependent cell models for the screening of anticancer prodrugs. Lastly, CYP4F2-specific targeted quantification was used to confirm the mechanism underlying a potential drug-drug interaction between warfarin and lovastatin. UPLC-MRM-based targeted proteomic techniques have many advantages, but the cost and time required for method development rises linearly with an increase in the number of targeted proteins. An emerging technique utilizing label-free data independent analysis (DIA) with high-resolution mass spectrometry (HDMS) offers the global quantification of hundreds of proteins at a negligible cost; however, there are numerous hurdles when using this technique. We introduced a new sample processing method, quantitative filter-assisted sample preparation (qFASP), which allows full recovery and analysis of clean, digested proteomic peptides. With qFASP and additional optimized procedures, many of the hurdles encountered with DIA quantification… Advisors/Committee Members: Wang, Michael Z. (advisor), Stella, Valentino J. (cmtemember), Stobaugh, John F. (cmtemember), Berkland, Cory J. (cmtemember), Staudinger, Jeff L. (cmtemember).

Subjects/Keywords: Pharmaceutical sciences; Analytical chemistry; Drug-Metabolizing Enzymes; Liquid Chromatography; Mass Spectrometry Quantification; nanoUPLC-Q-TOF Data Independent Acquisition; Quantitative FASP; UPLC-MRM Targeted Proteomics

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

APA (6^th Edition):

Chen, Y. (2016). Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/25430

Chicago Manual of Style (16^th Edition):

Chen, Yao. “Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes.” 2016. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/25430.

MLA Handbook (7^th Edition):

Chen, Yao. “Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes.” 2016. Web. 26 Jan 2021.

Vancouver:

Chen Y. Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes. [Internet] [Doctoral dissertation]. University of Kansas; 2016. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/25430.

Council of Science Editors:

Chen Y. Mass Spectrometry-Based Quantitative Proteomics for Drug-Metabolizing Enzymes. [Doctoral Dissertation]. University of Kansas; 2016. Available from: http://hdl.handle.net/1808/25430

2. Xu, Chenshu. REGULATION OF DRUG METABOLISM AND INFLAMMATION BY PREGNANE X RECEPTOR.

Degree: PhD, Pharmacology & Toxicology, 2011, University of Kansas

URL: http://hdl.handle.net/1808/9708

► Liver-enriched nuclear receptor (NR) proteins regulate the expression and activity of several pivotal hepatic biochemical pathways including the uptake, metabolism and excretion of cholesterol, bile… (more)

▼ Liver-enriched nuclear receptor (NR) proteins regulate the expression and activity of several pivotal hepatic biochemical pathways including the uptake, metabolism and excretion of cholesterol, bile acids, glucose, and xenobiotic compounds from the body. The pregnane x receptor (PXR, NR1I2) was first identified in 1998 as a member of the NR superfamily. Over the past decade, it has been well established that PXR functions as a master-regulator of xenobiotic- and drug-inducible expression and activity of numerous genes that encode key members of the phase I and phase II metabolic enzymes, as well as several membrane transporter proteins. In this way, activation of PXR serves as the principal defense mechanism defending the body from toxic insult. Similarly, the PXR protein also forms the molecular basis of an important class of drug-drug interactions in the clinical setting. Moreover, ligand-activated PXR negatively regulates inflammatory processes in both liver and intestine. An integrated model is emerging to reveal a key role for the post-translational modification of PXR in the selective suppression of gene expression, and is opening the door to the study of completely new modes of PXR-mediated gene regulation. This dissertation contributes mainly to two key areas of PXR research: (1) Identification a novel PXR target gene- carboxylesterase 6 (Ces6); (2) a study of the SUMOylation and ubiquitination of PXR protein. The results presented in this dissertation were primarily obtained from mouse and cell-culture systems. Data presented here reveal that activation of the inflammatory response modulates the SUMOylation and ubiquitination status of ligand-bound PXR protein. The SUMOylation and ubiquitination of the PXR protein functions to feedback-repress the inflammatory and xenobiotic responses, respectively. Taken together, the data represent a likely mechanism and provides initial molecular details for the connection between the PXR signaling pathway and inflammation. Studies on post-translational modification of PXR indicate how this protein is converted from a positive regulator in drug metabolism into a transcriptional repressor in inflammatory response. Finally, detailed protocols for purification of mammalian proteins necessary to perform in vitro SUMOylation reactions are presented. Taken together, the work presented in this dissertation contributes to understanding the interface between PXR, drug metabolism, and inflammation, which is expected to produce new opportunities for the development of novel therapeutic strategies. Advisors/Committee Members: Staudinger, Jeff L. (advisor), Dobrowsky, Rick T (cmtemember), Shi, Honglian (cmtemember), Moise, Alex (cmtemember), Lundquist, Erik A. (cmtemember).

Subjects/Keywords: Pharmacology; Toxicology; Carboxylesterase; Constitutive androstane receptor; Inflammation; Pregnane x receptor; Sumoylation

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APA (6^th Edition):

Xu, C. (2011). REGULATION OF DRUG METABOLISM AND INFLAMMATION BY PREGNANE X RECEPTOR. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/9708

Chicago Manual of Style (16^th Edition):

Xu, Chenshu. “REGULATION OF DRUG METABOLISM AND INFLAMMATION BY PREGNANE X RECEPTOR.” 2011. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/9708.

MLA Handbook (7^th Edition):

Xu, Chenshu. “REGULATION OF DRUG METABOLISM AND INFLAMMATION BY PREGNANE X RECEPTOR.” 2011. Web. 26 Jan 2021.

Vancouver:

Xu C. REGULATION OF DRUG METABOLISM AND INFLAMMATION BY PREGNANE X RECEPTOR. [Internet] [Doctoral dissertation]. University of Kansas; 2011. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/9708.

Council of Science Editors:

Xu C. REGULATION OF DRUG METABOLISM AND INFLAMMATION BY PREGNANE X RECEPTOR. [Doctoral Dissertation]. University of Kansas; 2011. Available from: http://hdl.handle.net/1808/9708

University of Kansas

3. Pan, Pan. Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy.

Degree: PhD, Pharmacology & Toxicology, 2014, University of Kansas

URL: http://hdl.handle.net/1808/21637

► Aberrant neuron-glia interactions can contribute to a variety of neurodegenerative diseases. We have previously demonstrated that enhanced activation of Erb B2, which is a member… (more)

▼ Aberrant neuron-glia interactions can contribute to a variety of neurodegenerative diseases. We have previously demonstrated that enhanced activation of Erb B2, which is a member of the epidermal growth factor receptor (EGFR) family, can contribute to the development of diabetic peripheral neuropathy (DPN). In peripheral nerves, Erb B receptors are activated by various members of the neuregulin-1 (NRG1) family including NRG1 Type I, NRG1 Type II and NRG1 Type III to regulate Schwann cell growth, migration, differentiation and dedifferentiation. Alternatively, Erb B2 activity can be negatively regulated by association with the Erb B2-interacting protein, erbin. Since the effect of diabetes on the expression of NRG1 isoforms and erbin in peripheral nerve are unknown, the current study determined whether changes in NRG1 isoforms and erbin may be associated with altered Erb B2 signaling in DPN. Swiss Webster mice were rendered diabetic with streptozotocin (STZ) and after 12 weeks of diabetes, treated with erlotinib, an inhibitor of Erb B2 activation. Inhibition of Erb B2 signaling partially reversed several pathophysiologic aspects of DPN including a pronounced sensory hypoalgesia, nerve conduction velocity deficits and the decrease in epidermal nerve fiber innervation. We also observed a decrease of NRG1 Type III but an increase of NRG1 Type I level in diabetic sural nerves at early stage of diabetes. With disease progression, we detected reduced erbin expression and enhanced MAPK pathway activity in diabetic mice. Pharmacologic inhibition of Erb B2 suppressed MAPK activity in diabetic sural nerves. These results support that hyperglycemia may impair NRG1-Erb B2 signaling by disrupting the balance between NRG1 isoforms, decreasing the expression of erbin and correspondingly activating the MAPK pathway. Together, imbalanced NRG1 isoforms and downregulated erbin may contribute to the dysregulation of Erb B2 signaling in the development of DPN Advisors/Committee Members: Dobrowsky, Rick T (advisor), Staudinger, Jeff L (cmtemember), Moise, Alexander R (cmtemember), Shi, Honglian (cmtemember), Ackley, Brian D (cmtemember).

Subjects/Keywords: Pharmacology; Erlotinib; Intra epidermal nerve fibers; Nerve conduction velocity; Sensory hypoalgesia

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APA (6^th Edition):

Pan, P. (2014). Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/21637

Chicago Manual of Style (16^th Edition):

Pan, Pan. “Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy.” 2014. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/21637.

MLA Handbook (7^th Edition):

Pan, Pan. “Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy.” 2014. Web. 26 Jan 2021.

Vancouver:

Pan P. Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy. [Internet] [Doctoral dissertation]. University of Kansas; 2014. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/21637.

Council of Science Editors:

Pan P. Differential expression of neuregulin-1 isoforms and downregulation of erbin are associated with Erb B2 receptor activation in diabetic peripheral neuropathy. [Doctoral Dissertation]. University of Kansas; 2014. Available from: http://hdl.handle.net/1808/21637

4. Lichti-Kaiser, Kristin Nicole. Regulation of the Pregnane X Receptor Signaling Pathway.

Degree: PhD, Pharmacology & Toxicology, 2009, University of Kansas

URL: http://hdl.handle.net/1808/6188

► Liver-enriched nuclear receptors (NRs) collectively function as metabolic and toxicological `sensors' that mediate liver-specific gene-activation in mammals. NR-mediated gene-environment interaction regulates important steps in the… (more)

▼ Liver-enriched nuclear receptors (NRs) collectively function as metabolic and toxicological `sensors' that mediate liver-specific gene-activation in mammals. NR-mediated gene-environment interaction regulates important steps in the hepatic uptake, metabolism and excretion of glucose, fatty acids, lipoproteins, cholesterol, bile acids, and xenobiotics. While it is well-recognized that ligand-binding is the primary mechanism behind activation of NRs, recent research is revealing that multiple signal transduction pathways modulate NR-function in liver. The interface between specific signal transduction pathways and NRs helps to determine their overall responsiveness to various environmental and physiological stimuli. The pregnane x receptor (PXR, NR1I2) was identified in 1998 as a member of the NR superfamily of ligand-activated transcription factors. PXR is activated by a broad range of lipophilic compounds in a species-specific manner. The primary function ascribed to PXR is the homeostatic control of steroids, bile acids, and xenobiotics. This function is mediated through PXR's ability to coordinately activate gene expression and regulate the subsequent activity of phase I and phase II metabolic enzymes, as well as several membrane transporter proteins. While PXR likely evolved primarily to protect the liver from toxic assault, its activation also represents the molecular basis for an important class of drug-drug, herb-drug, and food-drug interactions. While ligand binding is the primary mode of PXR activation, several signal transduction pathways interface with the PXR protein to determine its overall responsiveness to environmental stimuli. Multiple signaling pathways modulate the activity of PXR, likely through direct alteration of the phosphorylation status of the receptor and its protein cofactors. Therefore, specific combinations of ligand binding and cell signaling pathways affect PXR-mediated gene activation and determine the overall biological response. This dissertation contributes to the molecular understanding of the regulation of PXR by novel agonists, cAMP-dependent protein kinase (PKA) signaling, and phosphorylation. The results presented here were primarily obtained from mouse and tissue culture systems. This dissertation identifies Tian Xian, a traditional Chinese herbal anti-cancer remedy, as a novel PXR activator. This evidence suggests that Tian Xian should be used cautiously by cancer patients taking chemotherapy due to its potential to increase the metabolism of co-administered medications. In addition, data presented here show that activation of PKA signaling modulates PXR activity in a species-specific manner. It is further revealed that PXR exists as phospho-protein in vivo and that the activation of PKA signaling modulates the phospho-threonine status of PXR. Finally, the potential phosphorylation sites within the PXR protein are identified. These phosphorylation sites are characterized, using a phosphomimetic and phospho-deficient site-directed mutagenesis based approach, based on their… Advisors/Committee Members: Staudinger, Jeff L. (advisor), Muma, Nancy (cmtemember), Dobrowsky, Rick T (cmtemember), Timmons, Lisa (cmtemember), Carrasco, Gonzalo A. (cmtemember).

Subjects/Keywords: Health sciences; Pharmacology; Cell signaling; Gene expression; Pregnane x receptor

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APA (6^th Edition):

Lichti-Kaiser, K. N. (2009). Regulation of the Pregnane X Receptor Signaling Pathway. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/6188

Chicago Manual of Style (16^th Edition):

Lichti-Kaiser, Kristin Nicole. “Regulation of the Pregnane X Receptor Signaling Pathway.” 2009. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/6188.

MLA Handbook (7^th Edition):

Lichti-Kaiser, Kristin Nicole. “Regulation of the Pregnane X Receptor Signaling Pathway.” 2009. Web. 26 Jan 2021.

Vancouver:

Lichti-Kaiser KN. Regulation of the Pregnane X Receptor Signaling Pathway. [Internet] [Doctoral dissertation]. University of Kansas; 2009. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/6188.

Council of Science Editors:

Lichti-Kaiser KN. Regulation of the Pregnane X Receptor Signaling Pathway. [Doctoral Dissertation]. University of Kansas; 2009. Available from: http://hdl.handle.net/1808/6188

5. Sun, Mengxi. UBIQUITINATION AND SUMOYLATION OF PREGNANE X RECEPTOR.

Degree: PhD, Pharmacology & Toxicology, 2015, University of Kansas

URL: http://hdl.handle.net/1808/21668

► Abstract Pregnane X receptor (PXR, NR1I2) is a ligand-activated nuclear receptor (NR) superfamily member expressed at high levels in the liver and intestine of mammals.… (more)

▼ Abstract Pregnane X receptor (PXR, NR1I2) is a ligand-activated nuclear receptor (NR) superfamily member expressed at high levels in the liver and intestine of mammals. PXR can be activated by a broad range of structurally diverse xenobiotics and endobiotics. As a key regulator of xenobiotic metabolism and clearance, activated PXR up-regulates the expression of genes encoding phase I (oxidation) and phase II (conjugation) metabolizing enzymes and phase III transporters to increase the metabolism and clearance of drugs and xenobiotics from the body, thus protecting the body from potential toxic insults. Besides xenobiotic metabolism and clearance, activation of PXR also involves in the regulation of many other important biochemical pathways, like inflammation and bile acid homeostasis. While ligand-binding is the primary mechanism for NRs activation, recent research indicates that post-translational modifications of NRs also help to determine their activities under different physiological conditions and represent new modes of regulation for NRs. Studies on post-translational modifications of PXR have just begun to emerge, how post-translational modifications regulate PXR activity is not well-understood. This dissertation focuses on ubiquitination and SUMOylation of PXR. These post-translational modifications of PXR were characterized and their effects on PXR activities were studied in both primary cultures of hepatocytes and immortalized cell lines. Data presented here indicate that PXR is a target of the ubiquitin proteasome system, and inhibition of proteasome activity decreases the transactivation of PXR. The E3s and SENPs (Sentrin-specific Protease) that regulate PXR SUMOylation and de-SUMOylation are identified. Utilizing the newly identified SENPs, SUMOylation is further confirmed to be indispensable for PXR to repress inflammatory response. Furthermore, the crosstalk between ubiquitination and SUMOylation at the level of PXR is explored. Our data indicate that SUMOylation increases the presence of ubiquitinated PXR, and many other substrates of ubiquitin. Taken together, this dissertation contributes to the understanding of post-translational modifications of PXR and their regulatory effects on drug metabolism and inflammation, which is expected to produce new opportunities for the development of novel and safe therapeutic strategies. Advisors/Committee Members: Staudinger, Jeff L (advisor), Dobrowsky, Rick T (cmtemember), Moise, Alexander R (cmtemember), Shi, Honglian (cmtemember), Neufeld, Kristi L (cmtemember).

Subjects/Keywords: Pharmacology; Toxicology; PXR; SUMOylation; ubiquitination

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

APA (6^th Edition):

Sun, M. (2015). UBIQUITINATION AND SUMOYLATION OF PREGNANE X RECEPTOR. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/21668

Chicago Manual of Style (16^th Edition):

Sun, Mengxi. “UBIQUITINATION AND SUMOYLATION OF PREGNANE X RECEPTOR.” 2015. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/21668.

MLA Handbook (7^th Edition):

Sun, Mengxi. “UBIQUITINATION AND SUMOYLATION OF PREGNANE X RECEPTOR.” 2015. Web. 26 Jan 2021.

Vancouver:

Sun M. UBIQUITINATION AND SUMOYLATION OF PREGNANE X RECEPTOR. [Internet] [Doctoral dissertation]. University of Kansas; 2015. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/21668.

Council of Science Editors:

Sun M. UBIQUITINATION AND SUMOYLATION OF PREGNANE X RECEPTOR. [Doctoral Dissertation]. University of Kansas; 2015. Available from: http://hdl.handle.net/1808/21668

6. Zhang, Liang. Pharmacological Induction of Molecular Chaperones Restores Mitochondrial Function in Hyperglycemically Stressed Sensory Neurons.

Degree: PhD, Pharmacology & Toxicology, 2012, University of Kansas

URL: http://hdl.handle.net/1808/10622

► Distal diabetic peripheral polyneuropathy (DPN) is a prevalent complication resulting from chronic hyperglycemia in diabetic patients. It is associated with incapacitating pain, foot ulceration, and… (more)

▼ Distal diabetic peripheral polyneuropathy (DPN) is a prevalent complication resulting from chronic hyperglycemia in diabetic patients. It is associated with incapacitating pain, foot ulceration, and lower-limb amputations and brings about physical and psychological burdens to a patient's quality of life and a large economic burden to the health care system. Despite the prevalence and severity of DPN, the development of therapies that have focused on "diabetes specific" targets has met with limited translational success. This is due, at least in part, to the fact that disease progression among individuals does not occur with temporal and/or biochemical uniformity. Thus, our innovative approach has explored the premise that it is not necessary to target a specific pathogenic mechanism to reverse DPN and that pharmacologic induction of cytoprotective molecular chaperones affords a novel mechanism to improve myelinated and unmyelinated fiber function in DPN. To this end, we established that KU-32, a novel, non-toxic small molecule inhibitor of the molecular chaperone heat shock protein 90 (Hsp90) was able to protect sensory neurons from glucotoxicity and decrease the symptoms of DPN in diabetic mice. However, despite KU-32's efficacy in improving the sensory deficits of DPN in diabetic mice, specific mechanisms of neuroprotection remain unidentified. Thus, this dissertation utilized variations of stable isotope labeling with amino acids in cell culture (SILAC) as a novel, unbiased and systematic approach to quantitatively study the effect of hyperglycemia and KU-32 on the mitochondrial proteomes from dorsal root ganglia (DRG) neurons and Schwann cells (SCs) as in vitro models of DPN. This dissertation provides the first quantitative characterization of the temporal effect of hyperglycemia on the SC proteome using SILAC. Specifically, hyperglycemia increased the expression of numerous mitochondrial proteins in SCs that regulate oxidative phosphorylation and anti-oxidant responses. Consistent with these observations, hyperglycemia did not induce superoxide production in SCs and this correlated with an increase in MnSOD and the extent of proton leak, which may function in reducing oxidative stress. Although hyperglycemia increased mitochondrial respiration, the increase in proton leak suggests that respiration is less efficient at producing ATP. However, this deficiency may be offset by the ability of hyperglycemia to increase glycolysis in SCs. In contrast, hyperglycemia decreased mitochondrial respiratory capacity in DRG sensory neurons and promoted a robust induction in superoxide production. Treatment of KU-32 antagonized the effect of hyperglycemia by decreasing mitochondrial superoxide levels and improving organellar bioenergetics in DRG neurons. These functional improvements correlated with the translational induction of MnSOD and mitochondrial chaperones by KU-32. Overall, studies in this dissertation provide evidence that sensory neurons and SCs have rather distinct energetic responses to hyperglycemia and that SCs… Advisors/Committee Members: Dobrowsky, Rick T (advisor), Staudinger, Jeff L. (cmtemember), Shi, Honglian (cmtemember), Blagg, Brian (cmtemember), Richter, Mark L (cmtemember).

Subjects/Keywords: Pharmacology; Chaperones; Diabetic neuropathy; Hyperglycemia; Mitochodrial dysfunction; Oxidative stress; Sensory neurons

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APA (6^th Edition):

Zhang, L. (2012). Pharmacological Induction of Molecular Chaperones Restores Mitochondrial Function in Hyperglycemically Stressed Sensory Neurons. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/10622

Chicago Manual of Style (16^th Edition):

Zhang, Liang. “Pharmacological Induction of Molecular Chaperones Restores Mitochondrial Function in Hyperglycemically Stressed Sensory Neurons.” 2012. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/10622.

MLA Handbook (7^th Edition):

Zhang, Liang. “Pharmacological Induction of Molecular Chaperones Restores Mitochondrial Function in Hyperglycemically Stressed Sensory Neurons.” 2012. Web. 26 Jan 2021.

Vancouver:

Zhang L. Pharmacological Induction of Molecular Chaperones Restores Mitochondrial Function in Hyperglycemically Stressed Sensory Neurons. [Internet] [Doctoral dissertation]. University of Kansas; 2012. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/10622.

Council of Science Editors:

Zhang L. Pharmacological Induction of Molecular Chaperones Restores Mitochondrial Function in Hyperglycemically Stressed Sensory Neurons. [Doctoral Dissertation]. University of Kansas; 2012. Available from: http://hdl.handle.net/1808/10622

University of Kansas

7. Zhang, Hongsheng. Identification and Biochemical Characterization of PGC-1beta-Interacting Proteins.

Degree: MS, Pharmacology & Toxicology, 2008, University of Kansas

URL: http://hdl.handle.net/1808/4341

► Nuclear receptors (NRs) are ligand-activated transcription factors. They regulate key biological processes including homeostasis of lipophilic molecules, organogenesis, development, and reproduction. The ability of NRs… (more)

▼ Nuclear receptors (NRs) are ligand-activated transcription factors. They regulate key biological processes including homeostasis of lipophilic molecules, organogenesis, development, and reproduction. The ability of NRs to regulate gene transcription is dependent upon their ability to directly binding to specific enhancer elements within the promoters of their target genes. While NRs directly bind to DNA, they lack the capacity to modify chromatin, unwind DNA, and recruit transcriptional machinery. All of these aforementioned processes represent key steps in the regulation of gene transcription. Therefore, the full functional activity of NRs depends upon their ability to interact with protein cofactors, termed coactivator and corepressor proteins. Metabolic syndrome is an emerging global epidemic characterized by a complex disorder that affects both glucose and lipid metabolism. Peroxisome proliferator-activated receptor-gamma (PPARg) co-activator-1alpha (PGC-1a) is a coactivator protein that is mainly expressed in tissues that require a high oxidative capacity such as fat, muscle, brain, and liver. PGC-1a plays an important role in regulating key metabolic processes involved in energy homeostasis including gluconeogenesis, mitochondrial biogenesis, adaptive thermogenesis, and b-oxidation of fatty acids. PGC-1a accomplishes this feature through its ability to interact with selected NRs and certain other transcription factor types. PGC-1b is the closest homolog of PGC-1a and also shares some similarities with PGC-1a in amino acid sequence, expression pattern, interacting protein partners, target genes, and biochemical function. However, these two coactivator proteins also display distinct proerties. For example, PGC-1b mediates hepatic lipogenic program but not gluconeogenesis, whereas PGC-1a plays a key regulatory role in hepatic gluconeogenesis but has no effects upon lipogenesis. We therefore hypothesized that the key biological and functional differences between these two coactivator proteins is due to their distinct protein interaction profile. A comparison of the primary amino acid sequence of PGC-1b and PGC-1a revealed that both proteins contain three NR-interaction motifs (-LXXLL-) with the first two being highly conserved in their N-termini, respectively. However, PGC-1b contains an additional and unique stretch of amino acid sequence that separates the second and third NR-interaction motif that is absent from PGC-1a. We therefore fused the cDNA encoding this N-terminal region of PGC-1b to the GAL4-DNA binding domain (GAL4-NBT3) and used this protein as `bait' to screen cDNA expression libraries from liver, brain, and embryo using the yeast two hybrid system to identify novel PGC-1b-interacting proteins. Three potential PGC-1b-interacting proteins were identified. The first is a NR protein called COUP-TF1. The second PGC-1b-interacting protein we identified is a protein phosphatase regulatory protein termed PP4R1. The third protein we identified as a PGC-1b-interacting protein is a member of the SWI/SNF family… Advisors/Committee Members: Staudinger, Jeff L. (advisor), Staudinger, Jeff L. (cmtemember), Dobrowsky, Rick T (cmtemember), Moskovitz, Jacob (cmtemember).

Subjects/Keywords: Health sciences; Pharmacology; Toxicology; Baf60a; Metabolic syndrome; Pgc-1b-interacting proteins; Pgc-1beta; Pp4r1; Yeast two-hybrid screen

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

APA (6^th Edition):

Zhang, H. (2008). Identification and Biochemical Characterization of PGC-1beta-Interacting Proteins. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/4341

Chicago Manual of Style (16^th Edition):

Zhang, Hongsheng. “Identification and Biochemical Characterization of PGC-1beta-Interacting Proteins.” 2008. Masters Thesis, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/4341.

MLA Handbook (7^th Edition):

Zhang, Hongsheng. “Identification and Biochemical Characterization of PGC-1beta-Interacting Proteins.” 2008. Web. 26 Jan 2021.

Vancouver:

Zhang H. Identification and Biochemical Characterization of PGC-1beta-Interacting Proteins. [Internet] [Masters thesis]. University of Kansas; 2008. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/4341.

Council of Science Editors:

Zhang H. Identification and Biochemical Characterization of PGC-1beta-Interacting Proteins. [Masters Thesis]. University of Kansas; 2008. Available from: http://hdl.handle.net/1808/4341

University of Kansas

8. Vasquez, Francisco Edmundo. Hyperglycemia Increases Mitochondrial Protein Expression in the Absence of Oxidative Stress.

Degree: MS, Pharmacology & Toxicology, 2008, University of Kansas

URL: http://hdl.handle.net/1808/4323

► Long-term diabetes may cause diabetic peripheral neuropathy (DPN). Hyperglycemic-induced oxidative stress is widely accepted as the contributing factor in the development of diabetic complications. The… (more)

Subjects/Keywords: Health sciences; Pharmacology; Toxicology; Diabetes; Oxidative stress; Schwann cells; Silac; Superoxide

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APA (6^th Edition):

Vasquez, F. E. (2008). Hyperglycemia Increases Mitochondrial Protein Expression in the Absence of Oxidative Stress. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/4323

Chicago Manual of Style (16^th Edition):

Vasquez, Francisco Edmundo. “Hyperglycemia Increases Mitochondrial Protein Expression in the Absence of Oxidative Stress.” 2008. Masters Thesis, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/4323.

MLA Handbook (7^th Edition):

Vasquez, Francisco Edmundo. “Hyperglycemia Increases Mitochondrial Protein Expression in the Absence of Oxidative Stress.” 2008. Web. 26 Jan 2021.

Vancouver:

Vasquez FE. Hyperglycemia Increases Mitochondrial Protein Expression in the Absence of Oxidative Stress. [Internet] [Masters thesis]. University of Kansas; 2008. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/4323.

Council of Science Editors:

Vasquez FE. Hyperglycemia Increases Mitochondrial Protein Expression in the Absence of Oxidative Stress. [Masters Thesis]. University of Kansas; 2008. Available from: http://hdl.handle.net/1808/4323

University of Kansas

9. Hughes, John Clayton. Disruption of Orolingual Behavior in Rats Treated with Atypical Antipsychotic Drugs.

Degree: MS, Pharmacology & Toxicology, 2008, University of Kansas

URL: http://hdl.handle.net/1808/4340

► The atypical antipsychotics are a group of second generation drugs used for the treatment of schizophrenia, schizoaffective disorder, as well as some forms of bipolar… (more)

▼ The atypical antipsychotics are a group of second generation drugs used for the treatment of schizophrenia, schizoaffective disorder, as well as some forms of bipolar and major depressive disorder. First generation or the "typical antipsychotics" are an older group of drugs whose first member, chlorpromazine was developed in the early 1950's. The typical antipsychotics have a higher propensity to induce extrapyramidal side effects (EPS), and elevate prolactin levels. The introduction to this thesis begins with the history of the typical antipsychotics; particularly the introduction of chlorpromazine, up to the introduction of clozapine a compound which revolutionized the treatment of schizophrenia. Then the five subsequently approved atypical antipsychotic drugs are discussed. The introduction of clozapine soon revealed agranuocytosis as a relatively frequent side effect, and made it clear that a need remains for antipsychotics that are equally or more efficacious without deadly leukocytopenic side effects. While the atypical antipsychotics are often lumped into one category, they are diverse compounds with different EPS liabilities, side effects, and pharmacodynamic properties. Thus, the pharmacology of the atypical antipsychotics and the most interesting set of side effects, the extrapyramidal side effects are reviewed. Extrapyramidal side effects include akathisia, parkinsonism, dystonia, and tardive dyskinesia, and are complex motor side effects with mental components. This set of troublesome side effects often result in compliance issues particularly with the typical antipsychotics. Dopamine D2 receptor antagonism in the nigrostriatal pathways of the brain is believed to be the primary cause of extrapyramidal side effects. Dopamine D2 receptor antagonism in the mesolimbic dopamine pathway is thought to result in the antipsychotic affect, and compounds that target this pathway selectively are hypothesized to have lower EPS liabilities. Although the atypical antipsychotics are a diverse group of drugs they have some common features including lower extrapyramidal side effect liabilities, and minimal or no prolactin elevation. Within this context two major hypothesis' of atypicality will be reviewed, the fast-dissociation hypothesis and 5-HT2A/D2 affinity ratio hypothesis. Orolingual components of extrapyramidal side effects will be reviewed as well as neural control of the tongue by the hypoglossal nucleus, hypoglossal nucleus organization, and tongue anatomy, and physiology. Relevant preclinical behavioral research of both typical and atypical antipsychotics will be reviewed. The research presented here is concerned with both the acute and subchronic effects of the atypical antipsychotic on orolingual function in rats as a model of EPS. Licking behavior in rats is believed to be controlled by central pattern generators in the brainstem, and the rhythm (Hz) of licking, peak force, and the number of licks will be quantitatively analyzed and compared. Tolerance and sensitization will be assessed using a subchronic… Advisors/Committee Members: Fowler, Stephen C (advisor), Staudinger, Jeff L. (cmtemember), Moskovitz, Jacob (cmtemember).

Subjects/Keywords: Biology; Neurosciences; Antipsychotics; Clozapine; Extrapyramidal side effects; Hypoglossal; Orolingual; Power spectrum

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APA (6^th Edition):

Hughes, J. C. (2008). Disruption of Orolingual Behavior in Rats Treated with Atypical Antipsychotic Drugs. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/4340

Chicago Manual of Style (16^th Edition):

Hughes, John Clayton. “Disruption of Orolingual Behavior in Rats Treated with Atypical Antipsychotic Drugs.” 2008. Masters Thesis, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/4340.

MLA Handbook (7^th Edition):

Hughes, John Clayton. “Disruption of Orolingual Behavior in Rats Treated with Atypical Antipsychotic Drugs.” 2008. Web. 26 Jan 2021.

Vancouver:

Hughes JC. Disruption of Orolingual Behavior in Rats Treated with Atypical Antipsychotic Drugs. [Internet] [Masters thesis]. University of Kansas; 2008. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/4340.

Council of Science Editors:

Hughes JC. Disruption of Orolingual Behavior in Rats Treated with Atypical Antipsychotic Drugs. [Masters Thesis]. University of Kansas; 2008. Available from: http://hdl.handle.net/1808/4340

University of Kansas

10. Nair, Lakshmy. Development and validation of transgene constructs in order to generate bi-transgenic mice models for Diabetic Peripheral Neuropathy research.

Degree: MS, Pharmacology & Toxicology, 2010, University of Kansas

URL: http://hdl.handle.net/1808/6300

► Diabetic peripheral neuropathy (DPN), a common complication of diabetes, involves nerve damage in the arms and legs. Segmental demyelination is one of the basic patterns… (more)

▼ Diabetic peripheral neuropathy (DPN), a common complication of diabetes, involves nerve damage in the arms and legs. Segmental demyelination is one of the basic patterns observed in the pathology of DPN. Demyelinating neuropathies are those in which the Schwann cells (SCs) are primarily affected and these undergo substantial degeneration in diabetic neuropathy. Hence, it is of pertinence to investigate possible mechanisms which may contribute to the demyelination of SCs and the progression of DPN. To address this issue, this project aims to generate three different bi-transgenic mouse models that provide for the SC-specific expression of several transgenes that can be induced by the addition of the antibiotic doxycycline. For temporal, spatial and cell-specific control of transgene expression in mice, the above mentioned transgenes were constructed based on the Tet-On gene regulation system. In order to yield spatially regulated transgene expression, rtTA (reverse tetracycline transactivator) was placed under the control of the SC-specific promoter for 2', 3'-cyclic nucleotide 3'-phosphodiesterase. Placement of genes under the control of the rtTA- Ptight system has been shown to display excellent dose-response characteristics, which allows not only a qualitative off-on transition but also a fine tuning of gene expression and the study of quantitative aspects of gene activity. The above mentioned transgenes constructed in this project were validated in Hek293T cells to ensure that they expressed in a tight and highly inducible manner. The transgene transfected cell lines when treated with doxycycline showed a dose-dependent expression of the gene of interest. Maximum gene induction was observed when treated with 0.5ug/ml doxycycline. In the absence of doxycycline, almost no or minimal gene expression was observed. The transgenes were then excised out of the vector backbone for pronuclear microinjection. Once the transgenic mice are born, identified and validated, they shall be used for diabetic peripheral neuropathy research in the laboratory. Advisors/Committee Members: Dobrowsky, Rick T (advisor), Staudinger, Jeff L. (cmtemember), Davido, David (cmtemember).

Subjects/Keywords: Molecular biology; Biology; Neurosciences; Cell biology; Diabetic peripheral neuropathy; Schwann cells; Tet-on gene regulation system; Transgene construction; Transgene expression; Transgenic mouse model

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

APA (6^th Edition):

Nair, L. (2010). Development and validation of transgene constructs in order to generate bi-transgenic mice models for Diabetic Peripheral Neuropathy research. (Masters Thesis). University of Kansas. Retrieved from http://hdl.handle.net/1808/6300

Chicago Manual of Style (16^th Edition):

Nair, Lakshmy. “Development and validation of transgene constructs in order to generate bi-transgenic mice models for Diabetic Peripheral Neuropathy research.” 2010. Masters Thesis, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/6300.

MLA Handbook (7^th Edition):

Nair, Lakshmy. “Development and validation of transgene constructs in order to generate bi-transgenic mice models for Diabetic Peripheral Neuropathy research.” 2010. Web. 26 Jan 2021.

Vancouver:

Nair L. Development and validation of transgene constructs in order to generate bi-transgenic mice models for Diabetic Peripheral Neuropathy research. [Internet] [Masters thesis]. University of Kansas; 2010. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/6300.

Council of Science Editors:

Nair L. Development and validation of transgene constructs in order to generate bi-transgenic mice models for Diabetic Peripheral Neuropathy research. [Masters Thesis]. University of Kansas; 2010. Available from: http://hdl.handle.net/1808/6300

University of Kansas

11. Song, Peizhen. EFFECT OF BILE ACID FEEDING AND SEQUESTRATION ON LIVER BILE ACID COMPOSITION AND GENE REGULATION IN MICE.

Degree: PhD, Pharmacology, Toxicology & Therapeutics, 2010, University of Kansas

URL: http://hdl.handle.net/1808/7756

► The dissertation investigates the non-hepatotoxic doses of five bile acids (BAs) in the feed of mice, as well as adaptations in the expression of genes… (more)

▼ The dissertation investigates the non-hepatotoxic doses of five bile acids (BAs) in the feed of mice, as well as adaptations in the expression of genes involved in BA homeostasis and the possible roles of FXR-mediated signaling in regulating these genes. Mice were fed four main BAs, cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and lithocholic acid (LCA), and the therapeutic BA ursodeoxycholic acid (UDCA), at various concentrations in their diets (0.01, 0.03, 0.1, 0.3, 1.0, or 3.0%), as well as the BA sequestrant cholestyramine (resin) at 2% in their diets, for one week. Subsequently, serum alanine aminotransferase (ALT), serum and hepatic BA concentrations, as well as mRNAs of genes involved in BA homeostasis were quantified. The data showed: 1) LCA produced hepatotoxicity at 0.03%, indicated by increases in serum ALT and serum BA concentration, as did DCA at 0.1%, and CDCA and CA at 0.3% in the diet. UDCA at 0.3% in the diet might be hepatotoxic because the serum BA concentration was increased but the serum ALT did not increase. 2) Feeding BAs at hepatotoxic doses altered liver BA composition. 3) The mRNA of SHP and Cyp7a1 in the liver was increased by all doses of BAs. In contrast, BA regulation of the mRNA of the hepatic Cyp8b1 and the ileal Fgf15 are BA species dependent: CA and DCA at all doses increased Fgf15 and decreased Cyp8b1, whereas, CDCA and LCA at high doses increased Fgf15 and decreased Cyp8b1 mRNA. 4) Feeding resin increased the mRNA Cyp7a1 and Cyp8b1 in the liver and Fgf15 in the ileum. In conclusion, my dissertation demonstrates the non-hepatotoxic doses of individual BAs are as follows: 0.1% or lower in the diets for CA, CDCA, and UDCA, 0.03% for DCA, and 0.01% or lower for LCA. In addition, the altered liver BA composition after non-hepatotoxic doses of BA-feeding are able to trigger the hepatic FXR-SHP and the ileal FXR-Fgf15 signaling pathways, which coordinately regulate Cyp7a1 and Cyp8b1. Moreover, the the decreased expression of the ileal Fgf15 after feeding resin caused increases in mRNA expression of CYp7a1 and Cyp8b1. Advisors/Committee Members: Klaassen, Curtis D. (advisor), Copple, Bryan (cmtemember), Guo, Grace (cmtemember), Hagenbuch, Bruno (cmtemember), Staudinger, Jeff L. (cmtemember).

Subjects/Keywords: Toxicology; Pathology; Bile acids; Cholestyramine resin; Cyp7a1; Cyp8b1; Fgf15; Fxr

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

APA (6^th Edition):

Song, P. (2010). EFFECT OF BILE ACID FEEDING AND SEQUESTRATION ON LIVER BILE ACID COMPOSITION AND GENE REGULATION IN MICE. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/7756

Chicago Manual of Style (16^th Edition):

Song, Peizhen. “EFFECT OF BILE ACID FEEDING AND SEQUESTRATION ON LIVER BILE ACID COMPOSITION AND GENE REGULATION IN MICE.” 2010. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/7756.

MLA Handbook (7^th Edition):

Song, Peizhen. “EFFECT OF BILE ACID FEEDING AND SEQUESTRATION ON LIVER BILE ACID COMPOSITION AND GENE REGULATION IN MICE.” 2010. Web. 26 Jan 2021.

Vancouver:

Song P. EFFECT OF BILE ACID FEEDING AND SEQUESTRATION ON LIVER BILE ACID COMPOSITION AND GENE REGULATION IN MICE. [Internet] [Doctoral dissertation]. University of Kansas; 2010. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/7756.

Council of Science Editors:

Song P. EFFECT OF BILE ACID FEEDING AND SEQUESTRATION ON LIVER BILE ACID COMPOSITION AND GENE REGULATION IN MICE. [Doctoral Dissertation]. University of Kansas; 2010. Available from: http://hdl.handle.net/1808/7756

University of Kansas

12. Singh, Rakesh K. Novel Role of the JAK-STAT Pathway in Mediating the Effects of Atypical Antipsychotics on 5-HT2A Receptor Signaling.

Degree: PH.D., Pharmacology & Toxicology, 2008, University of Kansas

URL: http://hdl.handle.net/1808/5237

► The therapeutic benefits of atypical antipsychotics are proposed to be mediated by antagonism and subsequent desensitization of 5-HT2A receptor signaling; however, the mechanisms underlying this… (more)

▼ The therapeutic benefits of atypical antipsychotics are proposed to be mediated by antagonism and subsequent desensitization of 5-HT2A receptor signaling; however, the mechanisms underlying this desensitization response are not yet understood. We hypothesize that the desensitization of 5-HT2A receptors induced by atypical antipsychotics is dependent on activation of the JAK-STAT pathway. To test this hypothesis, we used a cell line, A1A1v cells, that natively expresses 5-HT2A receptor signaling system, and further confirmed the findings in rats. In A1A1v cells, we confirmed that treatment with both olanzapine and clozapine desensitizes 5-HT2A receptor signaling. Furthermore, olanzapine treatment also increased RGS7 mRNA and protein levels which were dependent on activation of JAK-STAT pathway. Similar results were found with MDL100907, a specific 5HT2A receptor antagonist; RGS7 protein and mRNA levels were increased along with activation of the JAK-STAT pathway, suggesting that antagonism of 5-HT2A receptors is sufficient to induce these changes. In addition, we also found an increase in STAT3 binding to the putative RGS7 promoter region with olanzapine treatment suggesting that the increase in RGS7 expression could be directly mediated by the JAK-STAT pathway. An increase in RGS protein could mediate desensitization of 5-HT2A receptor signaling by its GAP activity. Lastly, inhibition of the JAK-STAT pathway significantly attenuated olanzapine-induced desensitization of 5-HT2A receptor signaling in A1A1v cells. Similar findings were also observed in rats treated with olanzapine for 7 days. We found a decrease in 5-HT2A receptor-stimulated PLC activity in the frontal cortex which was dependent on activation of JAK-STAT pathway. Consistent with the cell culture data, the olanzapine-induced increase in RGS7 proteins and mRNA levels were dependent on activation of the JAK-STAT pathway. Olanzapine treatment significantly reduced plasma levels of oxytocin, adrenocorticotrophic hormone (ACTH), and corticosterone. Surprisingly, 5-HT2A receptor-stimulated oxytocin and corticosterone levels were also decreased in a dose-dependent manner by the JAK inhibitor whereas ACTH levels were not altered. Further studies are needed to investigate the role of the JAK-STAT pathway in the regulation of hormone levels. Taken together, these results from experiments in cells in culture and in rats suggest that increases in RGS7 expression via increased activation of the JAK-STAT pathway are necessary for antipsychotic-induced desensitization of 5-HT2A receptor signaling. Advisors/Committee Members: Muma, Nancy A. (advisor), Fowler, Stephen C. (cmtemember), Battaglia, George (cmtemember), Staudinger, Jeff L. (cmtemember), Carrasco, Gonzalo A. (cmtemember).

Subjects/Keywords: Health sciences; Pharmacology

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

APA (6^th Edition):

Singh, R. K. (2008). Novel Role of the JAK-STAT Pathway in Mediating the Effects of Atypical Antipsychotics on 5-HT2A Receptor Signaling. (Doctoral Dissertation). University of Kansas. Retrieved from http://hdl.handle.net/1808/5237

Chicago Manual of Style (16^th Edition):

Singh, Rakesh K. “Novel Role of the JAK-STAT Pathway in Mediating the Effects of Atypical Antipsychotics on 5-HT2A Receptor Signaling.” 2008. Doctoral Dissertation, University of Kansas. Accessed January 26, 2021. http://hdl.handle.net/1808/5237.

MLA Handbook (7^th Edition):

Singh, Rakesh K. “Novel Role of the JAK-STAT Pathway in Mediating the Effects of Atypical Antipsychotics on 5-HT2A Receptor Signaling.” 2008. Web. 26 Jan 2021.

Vancouver:

Singh RK. Novel Role of the JAK-STAT Pathway in Mediating the Effects of Atypical Antipsychotics on 5-HT2A Receptor Signaling. [Internet] [Doctoral dissertation]. University of Kansas; 2008. [cited 2021 Jan 26]. Available from: http://hdl.handle.net/1808/5237.

Council of Science Editors:

Singh RK. Novel Role of the JAK-STAT Pathway in Mediating the Effects of Atypical Antipsychotics on 5-HT2A Receptor Signaling. [Doctoral Dissertation]. University of Kansas; 2008. Available from: http://hdl.handle.net/1808/5237

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