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University of Southern California

1. Ravichandran, Monisha. Alcohol mediated expression of cyto-protective enzyme - NQO-1 and its post translational regulation.

Degree: MS, Biochemistry and Molecular Biology, 2012, University of Southern California

Chronic alcohol consumption leads to liver injury and death. Studies have shown ethanol causes increased inflammation, which leads to liver damage and cirrhosis. To counteract this inflammatory response, cells up-regulate antioxidant response genes, e.g. hemeoxygenase-1(HO-1) and NADH-quinone oxidoreductase-1(NQO-1). These cytoprotective genes are regulated by a central transcription factor, Nrf-2. Previous studies show ethanol induced mRNA levels of both HO-1 and NQO-1 in Kupffer cells involve activation of Nrf-2. In the present study, we examined whether ethanol affected the stability of NQO-1 mRNA, and transcription factors, i.e. Nrf-2 mRNA and Keap-1 mRNA, in endothelial cells. Our studies showed that ethanol increased the net expression of NQO-1, Nrf-2 and Keap-1 mRNAs in human endothelial cells (HMEC-1) in a time-dependent manner. Moreover, ethanol increased the stability of NQO-1 mRNA and Nrf-2 mRNA, while the Keap-1 mRNA was destabilized. Thus, we examined the role of microRNAs in the post-transcriptional regulation of NQO-1mRNA and Keap-1 mRNA. ❧ Our studies showed that both miR-566 and miR-518 attenuate the NQO-1 mRNA levels under basal and ethanol-treated conditions, as determined by transfection of HMEC-1 cells with miRs (synthetic mimics) and anti-miRs. We identified miR-200a as a potential candidate miRNA, which affects the Keap-1 mRNA expression. These studies for the first time, to the best of my knowledge, identify specific miRNAs, which may be involved in binding to the 3’UTR of NQO-1 mRNA and the 3’UTR of Keap-1 mRNA. These miRNAs may play an important role in affecting expression of cyto-protective genes and inflammation as observed in chronic alcoholic individuals. Advisors/Committee Members: Kalra, Vijay K. (Committee Chair), Tokes, Zoltan A. (Committee Member), Tahara, Stanley M. (Committee Member).

Subjects/Keywords: NQO-1; ethanol; miR-566; miR-518; miR-642; Nrf-2; Bach-1; Keap-1

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

APA (6th Edition):

Ravichandran, M. (2012). Alcohol mediated expression of cyto-protective enzyme - NQO-1 and its post translational regulation. (Masters Thesis). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/84016/rec/598

Chicago Manual of Style (16th Edition):

Ravichandran, Monisha. “Alcohol mediated expression of cyto-protective enzyme - NQO-1 and its post translational regulation.” 2012. Masters Thesis, University of Southern California. Accessed November 14, 2019. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/84016/rec/598.

MLA Handbook (7th Edition):

Ravichandran, Monisha. “Alcohol mediated expression of cyto-protective enzyme - NQO-1 and its post translational regulation.” 2012. Web. 14 Nov 2019.

Vancouver:

Ravichandran M. Alcohol mediated expression of cyto-protective enzyme - NQO-1 and its post translational regulation. [Internet] [Masters thesis]. University of Southern California; 2012. [cited 2019 Nov 14]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/84016/rec/598.

Council of Science Editors:

Ravichandran M. Alcohol mediated expression of cyto-protective enzyme - NQO-1 and its post translational regulation. [Masters Thesis]. University of Southern California; 2012. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/84016/rec/598

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