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- Title
Nicorandil Protects the Heart from Ischemia/Reperfusion Injury by Attenuating Endoplasmic Reticulum Response-induced Apoptosis Through PI3K/Akt Signaling Pathway.
- Authors
Wu, Hui; Ye, Ming; Yang, Jun; Ding, Jiawang; Yang, Jian; Dong, Wusong; Wang, Xinan
- Abstract
Background/Aims: As a vasodilatory drug used to treat angina, nicorandil has been shown to induce an infarct-limiting effect in various experimental animal models of myocardial ischemia-reperfusion (IR). There are multiple mechanisms causing the IR injury, among which, the endoplasmic reticulum (ER) stress and ER stress-initiated apoptosis are implicated to play an important role. However, whether ER stress is involved in nicorandil-induced cardioprotection is unknown. Methods: Post-ischemic functional recovery, lactate dehydrogenase (LDH) release and infarct size in perfused rat hearts subjected to global no-flow I/R were measured to analysis the effect of nicorandil and ER stress inducer of tunicamycin as well as phosphatidylinositol 3-kinase (PI3K) inhibitor of wortmannin on the I/R hearts. The I/R hearts tissue were harvested to evaluate apoptosis ratio with TUNEL assay and protein expression with western blot. Results: We showed that nicorandil ameliorated postischemic contractile recovery, as well as significantly reduced myocardial infarct size at a dose-dependent manner. Furthermore, nicorandil treatment inhibited the IR-induced apoptosis and ER stress. The beneficial effects of nicorandil were blocked by ER stress inducer, tunicamycin and specific phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. Concolusion: We conclude that the cardioprotection of nicorandil was at least in part mediated via inhibition of ER stress-induced apoptotic cell death through PI3K/Akt pathway. © 2015 S. Karger AG, Basel
- Subjects
REPERFUSION injury; NICORANDIL; ENDOPLASMIC reticulum; APOPTOSIS; PROTEIN kinase B; CELLULAR signal transduction; CARDIOTONIC agents
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2015, Vol 35, Issue 6, p2320
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000374035