Curcumin enhances cell-surface LDLR level and promotes LDL uptake through downregulation of PCSK9 gene expression in HepG2 cells

doi:10.1002/mnfr.201400366

CNU IR > Pharmacy and Science > Dept. of Biotechnology (including master's program) > Periodical Articles > Item 310902800/28535

Please use this identifier to cite or link to this item: https://ir.cnu.edu.tw/handle/310902800/28535

Title:	Curcumin enhances cell-surface LDLR level and promotes LDL uptake through downregulation of PCSK9 gene expression in HepG2 cells
Authors:	Tai, Mi-Hsueh Chen, Po-Kong Chen, Pei-Yi Wu, Ming-Jiuan Ho, Chi-Tang Yen, Jui-Hung
Contributors:	生物管理系
Keywords:	Curcumin HNF-1 alpha Hypercholesterolemia LDLR PCSK9
Date:	2014-11
Issue Date:	2015-05-06 21:19:46 (UTC+8)
Publisher:	Wiley-Blackwell
Abstract:	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.
Relation:	Molecular Nutrition & Food Research, v.58 n.11, pp.2133-2145
Appears in Collections:	[Dept. of Biotechnology (including master's program)] Periodical Articles

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