Novel Molecular Mechanisms of Regulation of Enzyme Cytochrome P4503A via Pregnane X Receptor

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dc.contributor.advisorGhose, Romi
dc.contributor.committeeMemberChow, Diana Shu-Lian
dc.contributor.committeeMemberHu, Ming
dc.contributor.committeeMemberMoorthy, Bhagavatula
dc.contributor.committeeMemberThevananther, Sundararajah
dc.creatorTaneja, Guncha
dc.date.accessioned2019-09-18T03:12:39Z
dc.date.available2019-09-18T03:12:39Z
dc.date.createdAugust 2017
dc.date.issued2017-08
dc.date.submittedAugust 2017
dc.date.updated2019-09-18T03:12:39Z
dc.description.abstractCytochrome P450 3A (CYP3A) is a family of Phase I drug metabolizing enzymes (DMEs) that metabolize up to 50% of currently clinically prescribed drugs. In humans, CYP3A family comprises of CYP3A4, 3A5, 3A7 and 3A43. Out of these enzymes, CYP3A4 is considered the most important contributor of hepatic drug metabolism in adults. Impairment in CYP3A4 gene expression/ activity leads to unanticipated adverse reactions or therapeutic failures; culminating in early termination of drug development or withdrawal of drugs from the market. Induction of gene expression of CYP3A4 is mainly regulated by basal regulators such as transcription factors and nuclear receptors including (Pregnane X Receptor (PXR). PXR, upon activation by xenobiotics, induces CYP3A4 gene and is largely considered responsible for its expression. On the other hand, gene expression and activity of CYP3A4 enzyme is down-regulated in many disorders such as hepatitis, diabetes, cancer, cardiovascular diseases etc. This alteration in CYP3A4 enzyme can cause harmful clinical consequences due to potentially dangerous drug-drug interactions. Therefore, a comprehensive understanding of the role of key regulators (i.e. transcription factors (TFs), epigenetic modulators, cell signaling pathways etc.) in transcriptional up or down-regulation of CYP3A4 is required to prevent disorders due to impaired drug metabolism. Hence, our objective was to identify key regulators and signaling pathways involved in PXR-mediated regulation of CYP3A4 enzyme in order to discover interventions for improved clinical therapy.
dc.description.departmentPharmacological and Pharmaceutical Sciences, Department of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10657/4840
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectCYP3A
dc.subjectPXR
dc.subjectMolecular regulation
dc.subjectJNK
dc.titleNovel Molecular Mechanisms of Regulation of Enzyme Cytochrome P4503A via Pregnane X Receptor
dc.type.dcmiText
dc.type.genreThesis
thesis.degree.collegeCollege of Pharmacy
thesis.degree.departmentPharmacological and Pharmaceutical Sciences, Department of
thesis.degree.disciplinePharmaceutics
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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