The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial KATP channels.

摘要: The cardioprotective effects of ischemic preconditioning (IPC) can be mimicked or blocked by pharmacologic agents, which modulate the mitochondrial ATP-sensitive potassium (mKATP) channel, thereby implicating this channel in mechanism IPC. Cardioprotection also achieved via inhibition respiratory complex II, and significant overlap exists between II inhibitors mKATP agonists. However, relationship remains unclear. Atpenin A5 (AA5) is a potent specific inhibitor, herein we report that AA5 (1 nM) activates protects against simulated ischemia-reperfusion (IR) injury isolated cardiomyocytes. Similar to known agonists, AA5-mediated protection was sensitive antagonists 5-hydroxydecanoate (5HD) glyburide. Notably, optimal opening protective concentration had no effect on enzymatic activity, suggesting an interaction with but not per se, necessary for protection. A observed perfused hearts, wherein increased post-IR contractile function decreased infarct size, 5HD-sensitive manner. In conclusion, inhibitor most activator discovered date, provides novel method activating channels protecting heart from IR injury.