Cardioprotective effect of MLN4924 on ameliorating autophagic flux impairment in myocardial ischemia-reperfusion injury by Sirt1.

Redox Biology
Ji ZhangBo Wei

Abstract

Neddylation is essential for cardiomyocyte survival in the presence of oxidative stress, and it participates in autophagy regulation. However, whether MLN4924-an inhibitor of neddylation-exerts cardioprotective effects against myocardial ischemia/reperfusion (MI/R) remains unknown. In the present study, MLN4924 exerted strong cardioprotective effects, demonstrated by significantly elevated cell viability, a decreased LDH leakage rate, and improved cell morphology following H2O2-induced injury in vitro. MLN4924 also markedly decreased the serum myocardial zymogram level, ameliorated cardiac histopathological alterations, and alleviated left ventricular contractile dysfunction, thus limiting the cardiac infarct size in vivo compared with those in MI/R mice. Amazingly, such action of MLN4924 was abrogated by a combined treatment with the autophagic flux inhibitor, chloroquine. The mRFP-GFP-LC3 assay illustrated that MLN4924 restored the defective autophagic flux via enhancing the autolysosome formation. Notably, the expression levels of Rab7 and Atg5 were markedly up-regulated in MLN4924 treated cells and mice subjected to H2O2 or MI/R, respectively, while knockdown of Sirt1 in cells and heart tissue largely blocked such effect an...Continue Reading

References

Nov 5, 2004·Nature·Akiko KumaNoboru Mizushima
Apr 29, 2006·Cell Death and Differentiation·A Hamacher-BradyA B Gustafsson
Mar 7, 2007·Current Topics in Developmental Biology·Devrim Gozuacik, Adi Kimchi
Apr 14, 2007·Cell Death and Differentiation·S Luo, D C Rubinsztein
Aug 16, 2008·Circulation Research·Kazuhiko NishidaKinya Otsu
Apr 11, 2009·Nature·Teresa A SoucySteven P Langston
Jul 24, 2010·British Journal of Pharmacology·J C McGrathC L Wainwright
Jul 24, 2010·British Journal of Pharmacology·Carol KilkennyUNKNOWN NC3Rs Reporting Guidelines Working Group
Aug 15, 2012·Autophagy·Xiucui MaAbhinav Diwan
May 23, 2013·Journal of Cellular Physiology·Fanny Ng, Bor Luen Tang
Jun 19, 2013·Biochimica Et Biophysica Acta·Vassiliki NikoletopoulouNektarios Tavernarakis
Sep 14, 2013·Methods in Molecular Biology·Erhe Gao, Walter J Koch
May 27, 2014·Biochimica Et Biophysica Acta·Sai MaFeng Cao
Sep 27, 2014·Cell Death and Differentiation·G FilomeniF Cecconi
Mar 12, 2016·Redox Biology·Ana Cristina Andérica-RomeroJosé Pedraza-Chaverri
May 31, 2016·International Journal of Cardiology·Xin-Xin ShuaiPing Luo
Jun 14, 2016·Cell Division·Danrui CuiYongchao Zhao
Apr 11, 2018·Proceedings of the National Academy of Sciences of the United States of America·Jianqiu ZouHuabo Su
Nov 3, 2020·Frontiers in Cellular Neuroscience·Jie LiuYi Yang
Feb 13, 2021·Trends in Cell Biology·Guang LuHan-Ming Shen

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