MSpace - DSpace at UofM >
Faculty of Graduate Studies (Electronic Theses and Dissertations) >
FGS - Electronic Theses & Dissertations (Public) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1993/4065

Title: Regulation of Cholesterol Biosynthesis in Hepatocytes
Authors: Enns, Jennifer Emily
Supervisor: O, Karmin (Animal Science/cross appointed Physiology)
Examining Committee: Shiu, Robert (Physiology) Siow, Chris (Physiology) Hatch, Grant (Pharmacology & Therapeutics)
Graduation Date: October 2010
Keywords: cholesterol
HepG2
hepatocytes
natural health product
nutraceutical
AMPK
lipoprotein
cardiovascular disease
atherosclerosis
statin
Issue Date: 23-Aug-2010
Abstract: Hypercholesterolemia, a condition of high cholesterol levels in the circulation, poses a major risk for developing cardiovascular disease, such as atherosclerosis. A common method of reducing plasma cholesterol levels relies on the administration of drugs that limit cholesterol synthesis or uptake, many of which have undesirable side effects. Thus, some patients are turning to an alternative treatment, namely natural health products. Natural health products are often equally or even more effective at treating illness than synthetic drugs and may produce fewer side effects. The goal of this study was to identify a natural health product that regulates hepatic cholesterol synthesis by inhibiting HMG-CoA reductase, the enzyme which catalyzes the rate-limiting step of the cholesterol synthesis pathway. Several natural compounds were screened using the human hepatoma cell line HepG2. One compound, berberine, showed great potential as a regulator of cholesterol synthesis and so became the subject of this investigation. Berberine inhibited HMG-CoA reductase activity and decreased cellular accumulation of cholesterol. Berberine was shown to regulate HMG-CoA reductase through activation of metabolic regulator AMP-activated protein kinase, which modifies HMG-CoA reductase post-translationally and thereby decreases its activity. In conclusion, this study demonstrates that the natural health product berberine decreases cholesterol synthesis by activating a cellular signalling pathway to bring about post-translational modification of HMG-CoA reductase, and in doing so, inhibits this enzyme. This novel mechanism supports berberine’s potential for a cholesterol-lowering therapy and its role in reducing the risk for cardiovascular disease.
URI: http://hdl.handle.net/1993/4065
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

Files in This Item:

File Description SizeFormat
Enns Regulation of Cholesterol Biosynthesis.pdf1.54 MBAdobe PDFView/Open
View Statistics

Items in MSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! MSpace Software Copyright © 2002-2010  Duraspace - Feedback