中山大学学报（医学科学版）2017，Vol.38Issue(6)：808-819,12.
RIP140通过抑制SIRT5表达介导心肌细胞能量代谢紊乱
Repression of SIRT5 is Involved in RIP140-mediated Metabolic Dysregulation in Cardiomyocytes
摘要
Abstract
[Objective]To investigate the effect of desuccinylase Sirtuin5 (SIRT5) on receptor-interacting protein 140 (RIP140)- mediated metabolic dysfunction in cardiomyocytes.[Methods]RIP140 was overexpressed by Adenovirus infection and SIRT5 was overexpressed by plasmid transfection. RIP140 and SIRT5 were knocked down by siRNA interference. The expression of RIP140 and SIRT5 were measured by qRT-PCR and western blot. The transcription levels of mitochondrial DNA-encoded genes were detected by qRT-PCR. Mitochondrial membrane potential was detected by tetramethylrhodamine ethyl ester(TMRE)fluorescence anl?ysis. Cellular oxygen consumption and ATP production were investigated by assay kits. All data are from at least three independent ex?periments.[Results]RIP140 overexpression significantly attenuated SIRT5 expression(P<0.05),whereas knockdown of endogenous RIP140 elevated SIRT5 expression(P<0.05)in cardiomyocytes. Superabundant RIP140 also induced hypersuccinylation of mitochon?drial proteins,suggesting RIP140 could repress the desuccinylase activity of SIRT5. Moreover,SIRT5 overexpression reversed RIP140-mediated mitochondrial dysfunction and energy metabolic impairment ,such as repression of mitochondrial DNA-encoded genes(P<0.05),decrease of mitochondrial membrane potential(P<0.05),as well as reduction of cellular oxygen consumption(P<0.05)and ATP production(P<0.05). Furthermore,the regulation of RIP140 on SIRT5 was dependent on the peroxisome proliferator-activated receptorα(PPARα)in cardiomyocytes.[Conclusion]RIP140 induces mitochondrial dysfunction and metabolic impairment through repression of SIRT5 in cardiomyocytes.关键词
SIRT5/RIP140/线粒体代谢/心肌代谢紊乱Key words
SIRT5/RIP140/mitochondrial metabolism/cardiac metabolic dysregulation分类
医药卫生引用本文复制引用
黄仪,陈艳芳,刘培庆..RIP140通过抑制SIRT5表达介导心肌细胞能量代谢紊乱[J].中山大学学报（医学科学版）,2017,38(6):808-819,12.基金项目
国家自然科学基金(81673433,81026548,81273499) （81673433,81026548,81273499）
国家自然科学基金青年科学基金项目(81402923) （81402923）
广东省自然科学基金合作项目(S2011030003190) （S2011030003190）
