Myocardial ischemia-reperfusion (I/R) injury is a well characterized process whereby mitochondrial permeability transition is triggered by reactive oxygen species (ROS) and is regulated in part by the mitochondrial transition pore (mPTP). Following mPTP opening, leakage of protein factors results in apoptosis or necrosis leading to myocardial damage. Clinical studies with compounds such as cyclosporine A have validated targeting mPTP as a strategy to reduce myocardial damage. Schaller et al. characterized 3,5-seco-4-nor-cholestan-5-one oxime-3-ol (TRO40303) as a cardioprotective agent that specifically binds to the cholesterol site on the mitochondrial translocator protein. Upon transport into the mitochondria, TRO40303 delayed mPTP opening and subsequent cell death in isolated rat cardiomyocytes, possibly through modulation of ROS production. In vivo TRO40303 reduced infarct size and the release of apoptosis inducing factor from mitochondria in the ischemic area at risk. TRO40303 represents a promising new tool to further explore the mechanism of mPTP opening and its role in I/R injury as well as a new class of drugs to treat myocardial reperfusion injury.
See article at J Pharmacol Exp Ther 2010, 333:696–706.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics