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http://ir.cnu.edu.tw/handle/310902800/28535
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標題: | Curcumin enhances cell-surface LDLR level and promotes LDL uptake through downregulation of PCSK9 gene expression in HepG2 cells |
作者: | Tai, Mi-Hsueh Chen, Po-Kong Chen, Pei-Yi Wu, Ming-Jiuan Ho, Chi-Tang Yen, Jui-Hung |
貢獻者: | 生物管理系 |
關鍵字: | Curcumin HNF-1 alpha Hypercholesterolemia LDLR PCSK9 |
日期: | 2014-11 |
上傳時間: | 2015-05-06 21:19:46 (UTC+8) |
出版者: | Wiley-Blackwell |
摘要: | Scope: Curcumin has been demonstrated as having numerous desirable characteristics, such as antioxidant, anti-inflammatory, and antiatherogenic activities. We report the hypocholesterolemic effect and molecular mechanism of curcumin. Methods and results: We found that curcumin enhanced LDL receptor (LDLR) level on the cell surface, as well as LDLR activity; however, LDLR transcription and mRNA stability were not affected. Furthermore, we found that proprotein convertase subtilisin/kexin type 9 (PCSK9) gene was downregulated at the transcriptional level by curcumin, leading to an increase in LDL uptake in HepG2 cells. The curcumin-responsive element of the PCSK9 promoter, a binding site for hepatocyte nuclear factor 1 alpha (HNF-1 alpha), was also identified. We demonstrated that curcumin reduced the nuclear abundance of hepatocyte nuclear factor 1 alpha, resulting in its attenuated interaction with the PCSK9 promoter and leading to a downregulation of PCSK9 expression. Finally, we showed that curcumin decreased the statin-induced PCSK9 expression and potentially synergized with statin administration. Conclusion: Current results indicate that curcumin suppression of PCSK9 expression is associated with increases in cell-surface LDLR and LDLR activity in hepatic cells and it acts in a molecular mechanism that is distinct from the statins. Curcumin exhibits hypolipidemic activity and may serve as a useful supplement to statin treatment for hypercholesterolemia. |
關聯: | Molecular Nutrition & Food Research, v.58 n.11, pp.2133-2145 |
Appears in Collections: | [生物科技系(所)] 期刊論文
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