RIP140通过抑制SIRT5表达介导心肌细胞能量代谢紊乱（英文）

发布时间：2018-03-19 20:42

本文选题：SIRT　切入点：RIP　出处：《中山大学学报(医学科学版)》2017年06期 　论文类型：期刊论文

【摘要】：【目的】探讨去琥珀酰化酶Sirtuin5(SIRT5)对受体相互作用蛋白140(RIP140)诱导的心肌线粒体能量代谢紊乱的影响。【方法】利用腺病毒感染心肌细胞诱导RIP140过表达,利用质粒转染诱导SIRT5基因过表达,si RNA干扰敲低RIP140、SIRT5表达;q RT-PCR和Western blot检测SIRT5、RIP140的表达变化;q RT-PCR检测线粒体编码基因的表达情况,TMRE染色法评估线粒体膜电位,试剂盒检测细胞耗氧和ATP生成情况。所有数据均来自至少3次的独立实验。【结果】过表达RIP140明显抑制SIRT5的表达(P0.05);敲低内源性RIP140能增加SIRT5的表达(P0.05)。过表达RIP140亦能诱导线粒体蛋白高度琥珀酰化,抑制SIRT5的去琥珀酰化酶活性。除此,RIP140能诱导线粒体功能紊乱和能量代谢损伤作用,表现为线粒体编码基因的表达抑制(P0.05),线粒体膜电位降低(P0.05),细胞耗氧和ATP合成减少(P0.05),而过表达SIRT5能抑制RIP140介导的上述能量代谢损伤(P0.05)。此外,SIRT5受RIP140的负性调控作用依赖于过氧化物增殖体激活受体α(PPARα)。【结论】RIP140通过抑制SIRT5诱导心肌细胞线粒体功能紊乱和能量代谢损伤。
[Abstract]:[objective] to investigate the effect of desuccinase Sirtuin5 (SIRT5) on mitochondrial energy metabolism disorder induced by receptor interaction protein 140 (RIP140). [methods] overexpression of RIP140 was induced by adenovirus infection in cardiomyocytes. Using plasmid transfection to induce the overexpression of SIRT5 gene, sisi RNA interference knock down RIP140 / SIRT5 expression, and Western blot to detect the expression change of SIRT5 / RIP140. TMRE staining was used to evaluate mitochondrial membrane potential (mtmp), and to detect the expression of Mitochondrial coding gene by RT-PCR. All the data were obtained from at least three independent experiments. [results] overexpression of RIP140 significantly inhibited the expression of SIRT5 P0.05A; knocking down endogenous RIP140 could increase the expression of SIRT5 P0.05; overexpression of RIP140 could also induce the expression of SIRT5. High succinylation of mitochondrial proteins, In addition to inhibiting the activity of SIRT5, RIP140 could induce mitochondrial dysfunction and damage to energy metabolism. The expression of mitochondrial coding gene was inhibited by P0.05G, mitochondrial membrane potential decreased P0.05N, cell oxygen consumption and ATP synthesis decreased P0.05N, while overexpression of SIRT5 inhibited P0.05G of the above mentioned energy metabolism damage mediated by RIP140. In addition, SIRT5 was negatively regulated by RIP140. [conclusion] RIP140 inhibits mitochondrial dysfunction and energy metabolism damage induced by SIRT5 in cardiomyocytes.
【作者单位】：中山大学药学院药理毒理实验室//新药成药性评估与评价国家地方联合工程实验室;广州医科大学附属第二医院药学部;
【基金】：国家自然科学基金(81673433,81026548,81273499);国家自然科学基金青年科学基金项目(81402923) 广东省自然科学基金合作项目(S2011030003190)
【分类号】：R96

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