title: 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.affiliation: Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China. xzwyjhx@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Huaixue
authors.initials: H
authors.lastname: Ji
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Xing
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Wen Wen
authors.initials: WW
authors.lastname: Cai
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, People's Republic of China. yfsxzyfsx@hotmil.com.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Guan
authors.affiliation: Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, People's Republic of China. yfsxzyfsx@sina.com.
authors.forename: Tie
authors.initials: T
authors.lastname: Xu
mesh_terms: D000107:Acetylation; D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000502:physiology*; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D005663:Furans / Q000494:pharmacology; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D011499:Protein Processing, Post-Translational; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D056565:Sirtuin 2 / Q000502:physiology*
chemical_list: C521855:AGK2 compound; C499515:FOXO3 protein, rat; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D000071316:Forkhead Box Protein O3; D005663:Furans; D011804:Quinolines; C097475:Sirt2 protein, rat; D056565:Sirtuin 2
keywords: Cell apoptosis; Deacetylation; Fas ligand; Forkhead box O transcription factor; Ischemia/reperfusion; SIRT2