Mechanistic studies on the cholesterol synthesis inhibition by gamma-tocotrienol in HepG2 cell model

• Main Authors: Yi-Huei Lin, 林怡慧
• Other Authors: Tzou-Chi Huang
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/46363600264381249332

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.