文献类型：期刊文献

英文题名：SIRT3 attenuates doxorubicin-induced cardiotoxicity by inhibiting NLRP3 inflammasome via autophagy

作者：Sun, Zhengzhu[1,2];Fang, Chongfeng[1,2];Xu, Shasha[1,2];Wang, Bin[1,2];Li, Danlei[1,2];Liu, Xiaoman[1,2];Mi, Yafei[1,2];Guo, Hangyuan[3];Jiang, Jianjun[1,2]

机构：[1]Wenzhou Med Univ, Dept Cardiol, Taizhou Hosp Zhejiang Prov, Zhejiang 317000, Peoples R China;[2]Wenzhou Med Univ, Lab Cardiovasc Dis, Taizhou Hosp Zhejiang Prov, Zhejiang 317000, Peoples R China;[3]Shaoxing Univ, Coll Med, 508 Huancheng W Rd, Shaoxing 312000, Zhejiang, Peoples R China

年份：2023

卷号：207

外文期刊名：BIOCHEMICAL PHARMACOLOGY

收录：SCI-EXPANDED(收录号：WOS:000899369800004)、、Scopus(收录号：2-s2.0-85143607631)、WOS

基金：Acknowledgements This research was supported by grants from Medical and Health Research Program of Zhejiang (No. 2020KY1034) , Medical and Health Research Program of Zhejiang (No. 2019KY775) , Public Welfare Tech-nology and Social Development Project of Zhejiang (No. LGF20H020008) , TCM Science and Technology Program of Zhejiang (No.2020ZB294) ,and Science and Technology Project of Taizhou (No. 22ywa09) .

语种：英文

外文关键词：SIRT3; Autophagy; Doxorubicin; Cardiotoxicity; NLRP3 Inflammasome

外文摘要：Doxorubicin (DOX) is a highly effective and extensively used chemotherapeutic drug but is limited by its car-diotoxicity. In our previous study, we showed that DOX-induced cardiotoxicity (DIC) triggers autophagy and pyroptosis. Sirtuin 3(SIRT3) is an NAD +-dependent deacetylase of the mitochondria that regulates autophagy. However, it is unknown if the protective effects of SIRT3 on DOX-induced cardiotoxicity involve the inhibition of NLRP3 inflammasome activation. In this study, we constructed in vivo and in vitro DIC models to investigate the effects and potential mechanisms of SIRT3 on DIC. We found that the overexpression of SIRT3 remarkably attenuated DIC through inhibition of the NLRP3 inflammasome. Moreover, we found that the overexpression of SIRT3 restored the dynamic balance of autophagosome/autolysosomes by targeting the mTOR/ULK1 signaling pathway. Application of the mTOR agonist MHY1485 further demonstrated that SIRT3 inhibited NLRP3 inflammasome activation by regulating autophagy. Collectively, the results suggest that SIRT3 effectively at-tenuates the cardiotoxicity of DOX and provides a theoretical foundation for further exploration of DIC.