American journal of physiology. Heart and circulatory physiology
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Am. J. Physiol. Heart Circ. Physiol. · Apr 2009
Transient opening of mitochondrial permeability transition pore by reactive oxygen species protects myocardium from ischemia-reperfusion injury.
Reactive oxygen species (ROS) production during ischemia-reperfusion (I/R) is thought to be a critical factor for myocardial injury. However, a small amount of ROS during the ischemic preconditioning (IPC) may provide a signal for cardioprotection. We have previously reported that the repetitive pretreatment of a small amount of ROS [hydrogen peroxide (H(2)O(2)), 2 microM] mimicked the IPC-induced cardioprotection in the Langendorff-perfused rat hearts. ⋯ In isolated permeabilized myocytes, H(2)O(2) (1 microM) accelerated the calcein leakage from mitochondria in a CsA-sensitive manner, indicating the opening of mPTP by H(2)O(2). However, H(2)O(2) did not depolarize mitochondrial membrane potential (DeltaPsi(m)) even in the presence of oligomycin (F(1)/F(0) ATPase inhibitor; 1 microM) and decreased mitochondrial Ca(2+) concentration ([Ca(2+)](m)) by accelerating the mitochondrial Ca(2+) extrusion via an mPTP. We conclude that the transient mPTP opening could be involved in the H(2)O(2)-induced cardioprotection against reperfusion injury, and the reduction of [Ca(2+)](m) without the change in DeltaPsi(m) might be a possible mechanism for the protection.