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dc.contributor.supervisor O, Karmin (Animal Science/cross appointed Physiology) en
dc.contributor.author Enns, Jennifer Emily
dc.date.accessioned 2010-08-23T19:18:18Z
dc.date.available 2010-08-23T19:18:18Z
dc.date.issued 2010-08-23T19:18:18Z
dc.identifier.uri http://hdl.handle.net/1993/4065
dc.description.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. en
dc.format.extent 1575136 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.rights info:eu-repo/semantics/openAccess
dc.subject cholesterol en
dc.subject HepG2 en
dc.subject hepatocytes en
dc.subject natural health product en
dc.subject nutraceutical en
dc.subject AMPK en
dc.subject lipoprotein en
dc.subject cardiovascular disease en
dc.subject atherosclerosis en
dc.subject statin en
dc.title Regulation of Cholesterol Biosynthesis in Hepatocytes en
dc.type info:eu-repo/semantics/masterThesis
dc.degree.discipline Physiology en
dc.contributor.examiningcommittee Shiu, Robert (Physiology) Siow, Chris (Physiology) Hatch, Grant (Pharmacology & Therapeutics) en
dc.degree.level Master of Science (M.Sc.) en
dc.description.note October 2010 en


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