Liu Ban, Che Wenliang, Zheng Changzhu, Liu Weijing, Wen Jing, Fu Haitao, Tang Kai, Zhang Jinying, Xu Yawei
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China.
Cell Physiol Biochem. 2013;32(4):1050-9. doi: 10.1159/000354505. Epub 2013 Oct 31.
SIRT5 is located in the mitochondria, and plays a crucial role in the regulation of metabolic process and cellular apoptosis. Cardiomyocytes are abundant in mitochondria. However, the role of SIRT5 in oxidative stress-induced apoptosis is still unknown in cardiomyocytes.
Western blots analysis revealed that SIRT5 is significantly down-regulated in cardiomyocytes upon oxidative stress. MTT assay, DAPI staining, and caspase 3/7 activity assay were used to estimate apoptosis development. The result suggested that compared with the wild-type group, SIRT5 knockdown results in a marked reduction in cell viability, and a significant increase in the number of apoptotic cells and the caspase 3/7 activity. Protein immunoprecipitation revealed a direct interaction between Bcl-Xl and SIRT5. Apoptosis assay and western blot anaylsis suggested that SIRT5 levels could affect the levels of Bcl-Xl expression, but have no effect on the apoptosis development in Bcl-Xl knockdown cells.
This study reveals a novel role of SIRT5 in the regulation of oxidative stress-induced apoptosis in cardiomyocytes. Pharmacological interventions on SIRT5 expression may be useful in the treatment of oxidative stress-related cardiac injury.
SIRT5定位于线粒体，在代谢过程和细胞凋亡的调控中起关键作用。心肌细胞富含线粒体。然而，SIRT5在氧化应激诱导的心肌细胞凋亡中的作用仍不清楚。
蛋白质免疫印迹分析显示，氧化应激时心肌细胞中SIRT5显著下调。采用MTT法、DAPI染色和caspase 3/7活性测定评估细胞凋亡进展。结果表明，与野生型组相比，SIRT5基因敲低导致细胞活力显著降低，凋亡细胞数量和caspase 3/7活性显著增加。蛋白质免疫沉淀显示Bcl-Xl与SIRT5直接相互作用。凋亡检测和蛋白质免疫印迹分析表明，SIRT5水平可影响Bcl-Xl的表达水平，但对Bcl-Xl基因敲低细胞的凋亡进展无影响。
本研究揭示了SIRT5在调控氧化应激诱导的心肌细胞凋亡中的新作用。对SIRT5表达的药物干预可能有助于治疗氧化应激相关的心脏损伤。
