| Summary: | 碩士 === 國立屏東科技大學 === 生物科技系所 === 101 === HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway produces cholesterol. γ-Tocotrienol and farnesol has the similar chemical structure and both of them promote the degradation of HMG-CoA reductase. In this study, human hepatoma HepG2 cell line was used to investigate how γ-tocotrienol inactivate HMG-CoA reductase and reduce the biosynthesis of cholesterol. Red yeast rice contains several compounds collectively known as monacolins, substances known to inhibit cholesterol synthesis as well. One of these, monacolin K is a potent inhibitor of HMG-CoA reductase, and is also known as mevinolin or lovastatin. Western blot assay showed that γ-tocotrienol inhibited HMG-CoA reductase protein expression. γ-Tocotrienol and monacolin K were found to decrease total cholesterol in HepG2 cell in a dose dependent manner. γ-Tocotrienol treatment was found to inhibit the translocation of Ras inactivate in HepG2 cell by using confocal microscopy. Taken together, these data suggest that γ-tocotrienol inhibit isoprenylation, and leading to Ras inactivation, subsequently inhibiting HMG-CoA reductase protein expression, and reducing the biosynthesis of cholesterol.
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