Curcumin inhibits cellular cholesterol accumulation by regulating SREBP-1/caveolin-1 signaling pathway in vascular smooth muscle cells  

作　　者：Hao-yu YUAN Shuang-yu KUAN Xing ZHENG Hong-yan LING Yun-Bo YANG Peng-Ke YAN Kai LI Duan-Fang LIAO 

机构地区：[1]Division of Pharmacoproteomics, Institute of Pharmacy and Pharmacology University of South China, Hengyang 421001, China [2]Molecular Medicine Center and the Second Affiliated Hospital, Suzhou University, Suzhou 215004, China [3]Research Center of Life Science,University of South China, Hengyang 421001, China

出　　处：《Acta Pharmacologica Sinica》2008年第5期555-563,共9页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China （No 30470719 and 30770868）, the National Major Basic Research Program of China （973 Program, No 2006CB503808）.

摘　　要：Aim： To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. Methods： Morphological changes of atherosclerotic lesions taken from apoE knockout （apoE^-/-） mice were determined by hematoxylineosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin- 1 was quantified by Western blotting. Translocation and the expression of sterol response element-binding protein-1 （SREBP-1） were indirectly detected by an immunofluorescence analysis. Results： The administration of 20 mg.kg^-1.d^-1 curcumin to apoE^-/- mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5- fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells （VSMC） pretreated with 50 mg.L^-1 ox-lipid density lipoprotein（ox-LDL） for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations （12.5, 25, and 50 μmol.L^-1） for different durations （0, 6, 12, 24, and 48 h） significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free choles- terol accompanying the elevation of the caveolin- 1 expression level （approximately 3-fold）; the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetylLeu-Leu-norleucinal, a SREBP- 1 protease inhibitor, showed increased nuclear trans- location of SREBP-1, reduced caveolin-1 expression level, and upregulated cellu- lar lipid levels. Condusion： Curcumin inhibits ox-LDL-induced cholesterol accu- mulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP- 1.Aim： To investigate the protective effect and the possible mechanism of curcumin on anti-atherosclerosis. Methods： Morphological changes of atherosclerotic lesions taken from apoE knockout （apoE^-/-） mice were determined by hematoxylineosin staining. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC. The protein expression of caveolin- 1 was quantified by Western blotting. Translocation and the expression of sterol response element-binding protein-1 （SREBP-1） were indirectly detected by an immunofluorescence analysis. Results： The administration of 20 mg.kg^-1.d^-1 curcumin to apoE^-/- mice for 4 months induced a 50% reduction of atherosclerotic lesions and yielded a 5- fold increase in the caveolin-1 expression level as compared to the model group. Rat vascular smooth muscle cells （VSMC） pretreated with 50 mg.L^-1 ox-lipid density lipoprotein（ox-LDL） for 48 h increased cellular lipid contents, and stimulated SREBP-1 translocation, but decreased the caveolin-1 expression level. Lipid-loaded cells exposed to curcumin at various concentrations （12.5, 25, and 50 μmol.L^-1） for different durations （0, 6, 12, 24, and 48 h） significantly diminished the number and area of cellular lipid droplets, total cholesterol, cholesterol ester, and free choles- terol accompanying the elevation of the caveolin- 1 expression level （approximately 3-fold）; the translocation of SREBP-1 from the cytoplasm to the nucleus was inhibited compared with the models. Lipid-loaded VSMC exposed to N-acetylLeu-Leu-norleucinal, a SREBP- 1 protease inhibitor, showed increased nuclear trans- location of SREBP-1, reduced caveolin-1 expression level, and upregulated cellu- lar lipid levels. Condusion： Curcumin inhibits ox-LDL-induced cholesterol accu- mulation in cultured VSMC through increasing the caveolin-1 expression via the inhibition of nuclear translocation of SREBP- 1.

关 键 词：CURCUMIN cholesterol accumulation vascular smooth muscle cells CAVEOLIN-1 sterol response element-binding protein-1 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]