Curcumin up-regulates LDL receptor expression via the sterol regulatory element pathway in HepG2 cells.

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Dou X, Fan C, Wo L, Yan J, Qian Y, Wo X

Curcumin up-regulates LDL receptor expression via the sterol regulatory element pathway in HepG2 cells.

Planta Med. 2008 Sep;74(11):1374-9. doi: 10.1055/s-2008-1081316. Epub 2008 Aug 14.

PubMed ID

18704882 [ View in PubMed

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Abstract

Plasma low-density lipoprotein-cholesterol (LDL-C) is mainly taken up and cleared by the hepatocellular LDL receptor (LDL-R). LDL-R gene expression is regulated by the sterol regulatory element binding proteins (SREBPs). Previous studies have shown that curcumin reduces plasma LDL-C and has hypolipidemic and anti-atherosclerotic effects. Herein, we investigated the effect of curcumin on LDL-R expression and its molecular mechanism in HepG2 cells. Curcumin increased LDL-R expression (mRNA and protein) and the resultant uptake of DiI-LDL in a dose- and time-dependent manner. Using a GFP reporter system in a transfected HepG2/SRE-GFP cell line, we found that curcumin activated the sterol regulatory element of the LDL-R promoter. In HepG2/Insig2 cells, curcumin reversed the inhibition of LDL-R expression induced by Insig2 overexpression. These data demonstrate that curcumin increases LDL-R protein expression and uptake activity via the SREBPs pathway. These findings contribute to our further understanding of the cholesterol-lowering and anti-atherosclerotic effects of curcumin.