%0 Journal Article
%T Selective Inhibition of PKC¦Â2 Restores Ischemic Postconditioning-Mediated Cardioprotection by Modulating Autophagy in Diabetic Rats
%A Huang
%A Fengnan
%A Lei
%A Shaoqing
%A Su
%A Wating
%A Wang
%A Yafeng
%A Xia
%A Zhengyuan
%A Xia
%A Zhong-yuan
%A Zhang
%A Yuan
%A Zhou
%A Lu
%J -
%D 2020
%R https://doi.org/10.1155/2020/2408240
%X Diabetic hearts are more susceptible to myocardial ischemia/reperfusion (I/R) injury and less sensitive to ischemic postconditioning (IPostC), but the underlying mechanisms remain unclear. PKC¦Â2 is preferentially overactivated in diabetic myocardium, in which autophagy status is abnormal. This study determined whether hyperglycemia-induced PKC¦Â2 activation resulted in autophagy abnormality and compromised IPostC cardioprotection in diabetes. We found that diabetic rats showed higher cardiac PKC¦Â2 activation and lower autophagy than control at baseline. However, myocardial I/R further increased PKC¦Â2 activation and promoted autophagy status in diabetic rats. IPostC significantly attenuated postischemic infarct size and CK-MB, accompanied with decreased PKC¦Â2 activation and autophagy in control but not in diabetic rats. Pretreatment with CGP53353, a selective inhibitor of PKC¦Â2, attenuated myocardial I/R-induced infarction and autophagy and restored IPostC-mediated cardioprotection in diabetes. Similarly, CGP53353 could restore hypoxic postconditioning (HPostC) protection against hypoxia reoxygenation- (HR-) induced injury evidenced by decreased LDH release and JC-1 monomeric cells and increased cell viability. These beneficial effects of CGP53353 were reversed by autophagy inducer rapamycin, but could be mimicked by autophagy inhibitor 3-MA. It is concluded that selective inhibition of PKC¦Â2 could attenuate myocardial I/R injury and restore IPostC-mediated cardioprotection possibly through modulating autophagy in diabetes
%U https://www.hindawi.com/journals/jdr/2020/2408240/