NPC1L1 contributes to the inhibition of lipid accumulation induced by ezetimibe in RAW264.7 cells
- VernacularTitle:尼曼-匹克C1型类似蛋白1介导依泽替米贝对RAW264.7细胞脂质蓄积的抑制作用
- Author:
Liang LI
;
Haoyu YUAN
;
Zhenwang TANG
;
Weixia YU
;
Zhizhong XIE
;
Qinhui TUO
;
Duanfang LIAO
- Publication Type:Journal Article
- Keywords:
pharmacology;
ezetimibe;
macrophage;
lipid accumulation;
niemann-pick type C1 like-1;
inhibition
- From:
Chinese Pharmacological Bulletin
2009;25(12):1563-1566
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effect of intestinal cholesterol absorption inhibitor Ezetimibe on lipid accumulation in RAW264.7 cells and identify the underlying mechanism.Method RAW264.7 cells were pretreated with the indicated concentrations of Ezetimibe (0,0.003,0.01 and 0.03 mol·L~(-1))for 24 hours or pretreated with the optimal concentration(0.03 mol·L~(-1))of Ezetimibe for different periods (0,6,12 and 24 h),followed by incubation with 50 mg·L~(-1) oxLDL for 24 hours,then the number of intracellular lipid droplets and lipid content were measured by using oil red O staining and HPLC; the expression of NPC1L1 was measured by Western blot.Results Pretreatment with indicated concentrations of Ezetimibe caused a concentration-dependent inhibition of intracellular lipid accumulation;pretreatment with 0.03 mol·L~(-1) Ezetimibe caused a time-dependent inhibition of intracellular lipid accumulation.It was noted that pretreatment with 0.03 mol·L~(-1) Ezetimibe for 24 hours inhibited CE by about 47%+0.1% compared with control group(oxLDL alone).Immunoblotting results showed that NPC1L1 was expressed in RAW264.7 cells and it was down-regulated after Ezetimibe treatment.Conclusions Ezetimibe causes concentration-dependent and time-dependent inhibition of lipid accumulation in RAW264.7 cells;it also reduces NPC1L1 expression in RAW264.7 cells.
