Date of Graduation

2002

Document Type

Thesis

Degree Type

MS

College

Eberly College of Arts and Sciences

Department

Not Listed

Committee Chair

Lisa M. Salati

Committee Co-Chair

Peter Mathers

Committee Member

Diana Beattie

Committee Member

Richard Dey

Abstract

HepG2 cells were used as a model system to study the regulation of glucose-6- phosphate dehydrogenase (G6PD). Regulation of hepatic G6PD expression involves changes in the amount of G6PD pre-mRNA in the nucleus in the absence of changes in the transcription rate of the gene. G6PD expression is increased in HepG2 cells incubated with increasing glucose concentrations. G6PD mRNA is increased 3- to 4- fold by incubation in 25 mM glucose, as compared to 0 mM glucose. To determine the cis-acting element involved in this regulation, HepG2 cells were stably transfected with G6PD genomic DNA composed of exons 7 through 13 and surrounding intronic DNA. Expression of this transgene was driven by the CMV promoter. Incubation with glucose resulted in a 3- to 4- fold increase in the amount of transgene mRNA. The future goal is to understand the molecular details of G6PD regulation by glucose in order to provide additional information into new mechanisms of post-transcriptional regulation.

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