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DIFFERENTIAL REGULATION OF MONOAMINE OXIDASE A AND B GENES
by
Boyang Wu
________________________________________________________________________
A Dissertation Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(MOLECULAR PHARMACOLOGY AND TOXICOLOGY)
December 2009
Copyright 2009 Boyang Wu
Object Description
| Title | Differential regulation of monoamine oxidase A and B genes |
| Author | Wu, Boyang |
| Author email | boyangwu@usc.edu; littletze@me.com |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Molecular Pharmacology & Toxicology |
| School | School of Pharmacy |
| Date defended/completed | 2009-10-22 |
| Date submitted | 2009 |
| Restricted until | Unrestricted |
| Date published | 2009-12-02 |
| Advisor (committee chair) | Shih, Jean C. |
| Advisor (committee member) |
Duncan, Roger F. Stiles, Bangyan L. Landolph, Joseph R. |
| Abstract | This study has investigated the transcriptional regulation of MAO A and B genes. MAO A and B are a crucial pair of oxidative isoenzymes, which degrade biogenic and dietary amines, including monoamine neurotransmitters, and produce hydrogen peroxide. Abnormal MAO A or B activity has been implicated in numerous neurological and psychiatric disorders. These two isoenzymes have different but overlapping substrate and inhibitor selectivity. There is a 70% amino acid sequences identity and different tissue- and cell-specific expression between the two enzymes. MAO A and B promoters share approximately 60% sequence identity with distinct organization. Both MAO A and B are regulated by Sp-family proteins, such as Sp1 and Sp3. MAO B is uniquely regulated by protein kinase C and mitogen-activated protein kinase signaling pathways, whereas MAO A is involved in the c-Myc-induced proliferative signaling pathway.; This study further demonstrates the similar and unique transcriptional regulation of MAO A and B genes. The results show that the SRY (the sex-determining region Y) gene activates the MAO A but not the MAO B gene; in contrast, the antioxidant t-butylhydroquinone (tBHQ) only represses MAO B activity. The SRY gene, encoding a putative transcription factor responsible for sex determination during embryogenesis, activates MAO A gene expression through a functional SRY-binding site in MAO A promoter, which is synergistically enhanced by Sp1. On the other hand, tBHQ represses MAO B activity through the Akt signaling pathway and cell cycle progression, and the downstream cyclin D1 directly regulates MAO B. Moreover, we demonstrate that RA activates MAO B transcription through both effective retinoic acid response elements and Sp1 sites in the promoter, which involves crosstalk between the retinoic acid receptor alpha and Sp1 in MAO B core promoter region.; In summary, these studies identified novel regulators of the MAO A and B genes and their molecular mechanisms and suggested novel potential role(s) of MAO in certain physiological processes and diseases states. The differential regulation of MAO A and B genes further supports the different physiological functions of these two isoenzymes. |
| Keyword | antioxidant; monoamine oxidase; promoter regulation; retinoic acid; sex-determining region Y gene; Sp1 |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m2781 |
| Rights | Wu, Boyang |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Wu-3365 |
| Archival file | uscthesesreloadpub_Volume40/etd-Wu-3365.pdf |
Description
| Title | Page 1 |
| Full text | DIFFERENTIAL REGULATION OF MONOAMINE OXIDASE A AND B GENES by Boyang Wu ________________________________________________________________________ A Dissertation Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (MOLECULAR PHARMACOLOGY AND TOXICOLOGY) December 2009 Copyright 2009 Boyang Wu |
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