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

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, s

SUBMITTER: Zhang J 

PROVIDER: S-EPMC8406034 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature