SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion
SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion
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DOI：
10.1007/s10495-016-1341-3
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发表时间：
2017-04-01
期刊：
影响因子：
7.2
通讯作者：
Xu, Tie
中科院分区：
文献类型：
--
作者：
Wang, Yan;Mu, Yu;Xu, Tie
我们发现Fas/FasL介导的“外源性”途径促进肾缺血损伤诱导的细胞凋亡。本研究旨在阐明肾缺血再灌注时FasL诱导的外源性通路的上游调控机制。结果表明，当SIRT 2被肾缺血再灌注激活时，激活的SIRT 2可与FOXO 3a结合并脱乙酰化，促进FOXO 3a核转位，导致核内FOXO 3a沿着增加，同时伴有FasL的表达和caspase 8、caspase 3的激活，从而在肾缺血再灌注过程中引发细胞凋亡。在肾缺血前给予SIRT 2抑制剂AGK 2可明显减少肾小管细胞凋亡，减轻肾小管超微结构损伤。这些结果表明，抑制FOXO 3a去乙酰化可能是一种有前途的治疗肾缺血/再灌注损伤的方法。
We have found that Fas/FasL-mediated "extrinsic" pathway promoted cell apoptosis induced by renal ischemic injury. This study is to elucidate the upstream mechanism regulating FasL-induced extrinsic pathway during renal ischemia/reperfusion. Results demonstrated that when SIRT2 was activated by renal ischemia/reperfusion, activated SIRT2 could bind to and deacetylate FOXO3a, promoting FOXO3a nuclear translocation which resulted in an increase of nuclear FOXO3a along with FasL expression and activation of caspase8 and caspase3, triggering cell apoptosis during renal ischemia/reperfusion. The administration of SIRT2 inhibitor AGK2 prior to renal ischemia decreased significantly the number of apoptotic renal tubular cells and alleviated ultrastructure injury. These results indicate that inhibition of FOXO3a deacetylation might be a promising therapeutic approach for renal ischemia /reperfusion injury.