pifithrin-mu and Myocardial-Infarction

p53 is well known as a regulator of apoptosis and autophagy. In addition, a recent study showed that p53 is a modulator of the opening of the mitochondrial permeability transition pore (mPTP), a trigger event of necrosis, but the role of p53 in necrosis induced by myocardial ischemia-reperfusion (I/R) remains unclear. The aim of this study was to determine the role of p53 in acute myocardial I/R injury in perfused mouse hearts. In male C57BL6 mice between 12 and 15 weeks of age, 2 types of p53 inhibitors were used to suppress p53 function during I/R: pifithrin-α, an inhibitor of transcriptional functions of p53, and pifithrin-μ, an inhibitor of p53 translocation from the cytosol to mitochondria. Neither infusion of these inhibitors before ischemia nor infusion for the first 30-minute period of reperfusion reduced infarct size after 20-minute ischemia/120-minute reperfusion. Infarct sizes were similar in p53 heterozygous knockout mice (p53

Topics: Animals; Benzothiazoles; Disease Models, Animal; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Necrosis; Sulfonamides; Time Factors; Toluene; Tumor Suppressor Protein p53; Ventricular Function, Left