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

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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.

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Acknowledgements

We are grateful to Dr. Mckaig, Donald R from the Rhode Island hospital, affiliated Hospital of Brown University USA, for proofreading. We thank Prof. Dong Hongyan, Department of Neurobiology of Xuzhou Medical College, for Ultramicroscopic Morphological observation of renal cell apoptosis. This work was supported by a grant from the Project of the National natural Science Foundation (No.81271267), the Project of the Natural Science Foundation of Jiangsu province (Nos. BK2010171 and BK20161179),and the Project of the Natural Science Foundation of Xuzhou (Nos. XZZD1338 and KC15SH047).

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    Authors and Affiliations

    1. Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China

      Yan Wang, Yu Mu, Xiaorui Zhou, Huaixue Ji, Xing Gao & Wen Wen Cai

    2. Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, People’s Republic of China

      Qiuhua Guan

    3. Institute of Emergency Rescue Medicine, Xuzhou Medical University, Xuzhou, 221002, People’s Republic of China

      Tie Xu

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    1. Yan Wang
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    Wang, Y., Mu, Y., Zhou, X. et al. SIRT2-mediated FOXO3a deacetylation drives its nuclear translocation triggering FasL-induced cell apoptosis during renal ischemia reperfusion. Apoptosis 22, 519–530 (2017). https://doi.org/10.1007/s10495-016-1341-3

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