Melatonin Alleviates Cardiac Dysfunction Via Increasing Sirt1-Mediated Beclin-1 Deacetylation and Autophagy During Sepsis

作者全名："Pi, Qiang-Zhong; Wang, Xiao-Wen; Jian, Zhao-Lei; Chen, Dan; Zhang, Cheng; Wu, Qing-Chen"

作者地址："[Pi, Qiang-Zhong] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing 400016, Peoples R China; [Wang, Xiao-Wen; Chen, Dan; Zhang, Cheng; Wu, Qing-Chen] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing 400016, Peoples R China; [Jian, Zhao-Lei] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Cardiothorac Surg, Shanghai 200233, Peoples R China; [Chen, Dan; Zhang, Cheng] Queen Mary Univ London, William & Larvey Res Inst, Ctr Clin Pharmacol, London EC1M 6BQ, England"

通信作者："Wang, XW (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiothorac Surg, Chongqing 400016, Peoples R China."

来源：INFLAMMATION

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000607961000001

JCR分区：Q2

影响因子：5.1

年份：2021

卷号：44

期号：3

开始页：1184

结束页：1193

文献类型：Article

关键词：Beclin-1; acetylation; autophagy; sepsis; cardiac dysfunction

摘要："Cardiac dysfunction is a major cause leading to multiple organ failure in sepsis. Beclin-1-dependent autophagy has been evidenced to exert protective effects on hearts in sepsis. However, the mechanisms on how Beclin-1 and autophagy are regulated remains enigmatic. To explore the detailed mechanisms controlling Beclin-1-dependent autophagy in septic heart and whether melatonin could protect against sepsis via regulating cardiac autophagy, adult Sprague-Dawley (SD) rats were subjected to cecal ligation and puncture (CLP) to induce sepsis. Rats were intraperitoneally administrated with 30 mg/kg melatonin within 5-min post-CLP surgery. Our data showed that sepsis induced Becline-1 acetylation and inhibited autophagy in hearts, resulting in impaired cardiac function. However, melatonin treatment facilitated Beclin-1 deacetylation and increased autophagy in septic hearts, thus improved cardiac function. Moreover, melatonin increased the expression and activity of Sirtuin 1 (Sirt1), and inhibition of Sirt1 abolished the protective effects of melatonin on Beclin-1 deacetylation and cardiac function. In conclusion, increased Beclin-1 acetylation was involved in impaired autophagy in septic hearts, while melatonin contributed to Beclin-1 deacetylation via Sirt1, leading to improved autophagy and cardiac function in sepsis. Our study sheds light on the important role of Beclin-1 acetylation in regulating autophagy in sepsis and suggests that melatonin is a potential candidate drug for the treatment of sepsis."

基金机构：National Natural Science foundation of ChinaNational Natural Science Foundation of China (NSFC) [NSFC81700320]; Chongqing Science and Technical Commission Basic Research Funding [CSTC 2019JCY-MSXMX0827]; Basic Research Training Project of the First Affiliated Hospital of Chongqing Medical University [PyJJ2017-11]

基金资助正文："This research was funded by the National Natural Science foundation of China (NSFC81700320), Chongqing Science and Technical Commission Basic Research Funding (CSTC 2019JCY-MSXMX0827) and Basic Research Training Project of the First Affiliated Hospital of Chongqing Medical University (PyJJ2017-11)."