Inhibition of hypothermic preservation-induced Smac/DIABLO protein expression by diazoxide in donor rat myocardium

AIM: To investigate the effect of a mitochondrial ATP-sensitive potassium channel(mitoKATP) opener diazoxide(DE) on Smac/DIABLO protein expressions in rat heart suffered from different duration of hypothermic preservation.METHODS: The Langendorff model of isolated rat heart was used.After stored in 4 ℃ Celsior solution with or without DE(30 μmol/L) for different time(0,3,6,9 or 12 h).Cell apoptosis was detected by TUNEL technique.The expression of Smac/DIABLO protein in cytoplasm and total caspase-3 protein in myocardia tissue was also analyzed by Western blotting.RESULTS:(1) Compared to the hypothermic preservation groups,DE reduced the percentage of apoptotic cells and the expression of caspase-3 protein in myocardia tissue.(2) The peak of Smac/DIABLO protein expression level appeared at 6 h after hypothermic preservation,and which was postponed to 9 h by DE.(3) The above effects of DE were attenuated by a mitoKATP channel inhibitor 5-hydroxydecanoate(5-HD).CONCLUSION: The findings indicate that in the isolated rat heart,DE protects myocardium against different duration of hypothermic preservation injury via opening of mitoKATP channel and inhibition of Smac/DIABLO protein expression.