Activation of autophagy in ischemic postconditioning contributes to cardioprotective effects against ischemia/reperfusion injury in rat hearts.
We tested the hypothesis that ischemic postconditioning (IPost) induces autophagy and the activation of autophagy contributes to the cardioprotective effects against ischemia/reperfusion injury in rat hearts. Rats were subjected to IPost established by 3 cycles of 10-second reperfusion followed by 10-second ischemia at the end of 30-minute ischemia. The activation of autophagy was assessed by the morphological and biochemical examinations after 120-minute reperfusion in ventricular tissue. To investigate the contribution of autophagy to IPost, the rats were pretreated with the autophagy inhibitor 3-methyl-adenine (3-MA). We found that IPost increased the formation of autophagic vacuoles, the autophagic-related protein levels of LC3-II, Beclin1, lysosome-associated membrane protein 2, and cathepsin D, and the mRNA level of LC3 and Beclin1 in the risk zone of the postconditioned hearts. Furthermore, 3-MA treatment significantly reversed the reduction effect of IPost on infarct volume, and in the meantime, inhibited the induction of LC3 and Beclin1. In addition, 3-MA treatment inhibited the antiapoptotic-related protein levels of Bcl-2 and increased the apoptotic-related protein levels of Bad. Taken together, these results indicate that the protective effects of IPost are associated with the activation of autophagy in rat hearts.
Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Chao
C
Wei
Hongxia
H
Li
Lianhua
L
Han
Lei
L
Zhang
Xiangjun
X
Yang
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D015153:Blotting, Western; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D057775:Ischemic Postconditioning; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
D000225:Adenine; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D017931:DNA Primers; D008869:Microtubule-Associated Proteins; C512829:Becn1 protein, rat; C526109:Anxa3 protein, rat; C025946:3-methyladenine