Curcumin Upregulates LDL Receptor Expression via Sterol Regulatory Element Pathway in HepG2 Cells

摘要

@@Objective: Plasma low-density lipoprotein-cholesterol (LDL-C) is mainly taken up and cleared by 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,the authors investigated the effect of curcumin on LDL-R expression and its molecular mechanism in HepG2 cells.Methods & Results: 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,the authors found that eurcumin activated the sterol regulatory element of LDL-R promoter.In HepG2/Insig2 cells,curcumin reversed the inhibition of LDL-R expression induced by Insig2 overexpression.Conclusion: These data demonstrate that curcumin increases LDL-R protein expression and uptake activity via the SREBPs pathway.These findings contribute to further understanding of the cholesterol-lowering and anti-atherosclerotic effects ofcurcumin.