Regulation of Cholesterol Biosynthesis in Hepatocytes

dc.contributor.authorEnns, Jennifer Emily
dc.contributor.examiningcommitteeShiu, Robert (Physiology) Siow, Chris (Physiology) Hatch, Grant (Pharmacology & Therapeutics)en
dc.contributor.supervisorO, Karmin (Animal Science/cross appointed Physiology)en
dc.date.accessioned2010-08-23T19:18:18Z
dc.date.available2010-08-23T19:18:18Z
dc.date.issued2010-08-23T19:18:18Z
dc.degree.disciplinePhysiologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractHypercholesterolemia, 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.description.noteOctober 2010en
dc.format.extent1575136 bytes
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/1993/4065
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectcholesterolen
dc.subjectHepG2en
dc.subjecthepatocytesen
dc.subjectnatural health producten
dc.subjectnutraceuticalen
dc.subjectAMPKen
dc.subjectlipoproteinen
dc.subjectcardiovascular diseaseen
dc.subjectatherosclerosisen
dc.subjectstatinen
dc.titleRegulation of Cholesterol Biosynthesis in Hepatocytesen
dc.typemaster thesisen_US
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