SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion.

Abstract	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.
Authors	Yan Wang, Yu Mu, Xiaorui Zhou, Huaixue Ji, Xing Gao, Wen Wen Cai, Qiuhua Guan, Tie Xu
Journal	Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 22 Issue 4 Pg. 519-530 (Apr 2017) ISSN: 1573-675X [Electronic] Netherlands
PMID	28078537 (Publication Type: Journal Article)
Chemical References	AGK2 compound FOXO3 protein, rat Fas Ligand Protein Faslg protein, rat Forkhead Box Protein O3 Furans Quinolines Sirt2 protein, rat Sirtuin 2
Topics	Acetylation Active Transport, Cell Nucleus (physiology) Animals Apoptosis (physiology) Cell Nucleus (metabolism) Drug Evaluation, Preclinical Enzyme Activation Fas Ligand Protein (physiology) Forkhead Box Protein O3 (metabolism) Furans (pharmacology) Ischemia (metabolism, pathology) Kidney (blood supply, pathology) Male Protein Processing, Post-Translational Quinolines (pharmacology) Rats Rats, Sprague-Dawley Reperfusion Injury (metabolism, pathology) Sirtuin 2 (physiology)

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