Curcumin up-regulates LDL receptor expression via the sterol regulatory element pathway in HepG2 cells.
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.
Dou
Xiaobing
X
Life Science College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P. R. China.
Fan
Chunlei
C
Wo
Like
L
Yan
Jin
J
Qian
Ying
Y
Wo
Xingde
X
D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D011973:Receptors, LDL / Q000378:metabolism*; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*; D015854:Up-Regulation
D011973:Receptors, LDL; D051779:Sterol Regulatory Element Binding Proteins; D003474:Curcumin