dc.contributor.advisor | Tian, Yanan | |
dc.creator | Tan, Qiulin | |
dc.date.accessioned | 2006-04-12T16:02:30Z | |
dc.date.available | 2006-04-12T16:02:30Z | |
dc.date.created | 2005-12 | |
dc.date.issued | 2006-04-12 | |
dc.identifier.uri | https://hdl.handle.net/1969.1/3101 | |
dc.description.abstract | Oxygen balance is very important and tightly regulated in mammals. Under
hypoxia, hypoxia inducible factor 1(HIF-1) dimerizes with hypoxia inducible
factor 1± (HIF-) and activates expression of several genes. Using a
mammalian two hybrid assay, we found that HIF-1 interacted with sterol
response element binding protein 1a (SREBP1a). SREBP1a regulates
transcription of HMG-CoA reductase via binding to the sterol response element
(SRE) in the promoter region. HMG-CoA reductase is the rate-limiting enzyme in
cholesterol biosynthesis. The interaction between SREBP1a and HIF-1suggests that HIF-1 may play an important role in regulation of cholesterol
biosynthesis. We tested the effects of hypoxia on the HMG-CoA reductase. We
found that hypoxia caused suppression of SRE-driven luciferase reporter gene
expression. HMG-CoA reductase mRNA levels decreased under hypoxia in both
hepatoma cells and mouse primary hepatocytes. Electrophoretic mobility shift
assay showed that HIF-1 blocked binding of SREBP1a to the SRE sequence in
vitro. Ectopic expression of HIF-1 suppressed the SRE- driven luciferase
reporter gene expression in BPR cells (HIF-1). Our results suggest that
hypoxia inhibits cholesterol biosynthesis by suppressing SREBP1a-regulated gene expression and this suppression is caused by the blockage of SREBP1a
binding to SRE sequence by HIF-1. | en |
dc.format.extent | 495826 bytes | en |
dc.format.medium | electronic | en |
dc.format.mimetype | application/pdf | |
dc.language.iso | en_US | |
dc.publisher | Texas A&M University | |
dc.subject | cholesterol | en |
dc.subject | hypoxia | en |
dc.title | Inhibition of cholesterol biosynthesis under hypoxia | en |
dc.type | Book | en |
dc.type | Thesis | en |
thesis.degree.department | Veterinary Physiology and Pharmacology | en |
thesis.degree.discipline | Toxicology | en |
thesis.degree.grantor | Texas A&M University | en |
thesis.degree.name | Master of Science | en |
thesis.degree.level | Masters | en |
dc.contributor.committeeMember | Parrish, Alan R. | |
dc.contributor.committeeMember | Porter, Weston W. | |
dc.contributor.committeeMember | Safe, Stephen H. | |
dc.type.genre | Electronic Thesis | en |
dc.type.material | text | en |
dc.format.digitalOrigin | born digital | en |