Aim: To investigate whether mitochondrial calcium uniporter participates in the cardioprotection of tumor necrosis factor alpha (TNFalpha) pretreatment in isolated rat hearts subjected to ischemia/reperfusion.
Methods: Isolated perfused rat hearts were subjected to 30 min regional ischemia (occlusion of left anterior descending artery) and 120 min reperfusion. The infarct size, coronary flow (CF) and lactate dehydrogenase (LDH) release during reperfusion were measured. The mitochondria of the heart were isolated and suspended in the swelling buffer for measurement of absorbance at 520 nm.
Results: Pretreatment with TNFa at 10 U/ml for 7 min followed by 10 min washout reduced the infarct size and LDH release, and improved the recovery of CF during reperfusion. Administration of spermine (20 micromol/L), an opener of mitochondrial calcium uniporter, for 10 min during early reperfusion attenuated the reduction of infarct size and LDH release, and improvement of CF induced by TNFalpha. In isolated mitochondria of the heart pretreated with TNFalpha, the absorbance at 520 nm decreased less than that of mitochondria without TNFalpha pretreatment. Administration of spermine (50 micromol/L) attenuated the change of the absorbance induced by TNFalpha.
Conclusion: The findings indicate that TNFalpha protects myocardium against ischemia/reperfusion injury via inhibiting mitochondrial calcium uniporter opening as well as mitochondrial permeability transition pore opening.