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依泽替米贝通过SIRT1抑制血管平滑肌细胞源性荷脂细胞固醇调节元件结合蛋白1c的过度乙酰化

张弛 黄靓 罗其富 屈顺林 韦星 唐志晗 高治平

中国动脉硬化杂志2012,Vol.20Issue(6):519-522,4.
中国动脉硬化杂志2012,Vol.20Issue(6):519-522,4.

依泽替米贝通过SIRT1抑制血管平滑肌细胞源性荷脂细胞固醇调节元件结合蛋白1c的过度乙酰化

Ezetimibe Inhibit Hyperacetylation of SREBP-1c in Lipid-Loaded Cells Derived from VSMC Required for SIRT1

张弛 1黄靓 1罗其富 2屈顺林 1韦星 1唐志晗 1高治平2

作者信息

  • 1. 南华大学心血管疾病研究所动脉硬化学湖南省重点实验室,湖南省衡阳市421001
  • 2. 南华大学药物药理研究所,湖南省衡阳市421001
  • 折叠

摘要

Abstract

Aim The effect of ezetimibe ( EZE) on acetylation of sterol regulatory element binding protein-lc (SREBP-1 c) in lipid-loaded cells derived from vascular smooth muscle cell (VSMC) and its mechanisms have been explored. Methods The cholesterol: methyl-fi-cyclodextrin (Choi: MBCD) complexes were used to build VSMC-derived lipid-loaded cells. After treated by 30 u.mol/L EZE, the level of acetylated SREBP-1 c, the level of fatty acid synthase (FAS) protein expression in lipid-loaded cells were detected by western blot, and the interaction between SIRT1 and SREBP-1 c were analyzed by co-immunoprecipitation, and the role of SIRT1 in deacetylation of SREBP-1 c was investigated using shRNA-mediated protein knockdown. Results The level of acetylated SREBP-lc, the level of FAS protein expression were increased, but the interaction between SIRT1 and SREBP-lc was significantly reduced in lipid-loaded cells. However, EZE could weaken all these effects induced by Choi: MpCD in lipid-loaded cells. A further study reveals that effects of EZE in lipid-loaded cells could be abolished by SIRT1 shRNA transfection. Conclusion EZE inhibits hyperacetylation of SREBP-lc in lipid-loaded cells required for SIRT1.

关键词

依泽替米贝/血管平滑肌细胞/固醇调节元件结合蛋白1c/SIRT1/乙酰化修饰

Key words

Ezetimibe/Vascular Smooth Muscle Cell/Sterol Regulatory Element Binding Protein-lc/SIRT1/Acetylation

分类

医药卫生

引用本文复制引用

张弛,黄靓,罗其富,屈顺林,韦星,唐志晗,高治平..依泽替米贝通过SIRT1抑制血管平滑肌细胞源性荷脂细胞固醇调节元件结合蛋白1c的过度乙酰化[J].中国动脉硬化杂志,2012,20(6):519-522,4.

基金项目

湖南省教育厅基金项目(08C743) (08C743)

中国动脉硬化杂志

OA北大核心CSCDCSTPCD

1007-3949

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