Reactive oxygen species and mitochondrial KATP-sensitive channels mediated cardioprotection induced by TNF-alpha during hypoxia and reoxygenation / 生理学报

ABSTRACT

The aim of the present study was to testify whether the reactive oxygen species and mitochondrial ATP-sensitive potassium (K(ATP)) channels were involved in the cardioprotection induced by tumor necrosis factor alpha (TNF-alpha) in the cultured neonatal ventricular myocytes suffered from 12 h of hypoxia and 6 h of reoxygenation. We tested the release of lactate dihydrogenase (LDH) and manganese superoxide dismutase (Mn-SOD) with spectrophotometry. It was shown that pretreatment with TNF-alpha (10, 50, 100, or 500 U/ml) significantly increased the Mn-SOD activity and reduced LDH release in the neonatal ventricular myocytes subjected to hypoxia and reoxygenation. Pretreatment with NAC (1 mmol/L), antimycin A (50 micromol/L), 2-MPG (400 micromol/L), DDC (100 nmol/L) or 5-HD (100 micromol/L), respectively, attenuated the increase in Mn-SOD activity and reduction of LDH level induced by TNF-alpha in ventricular myocytes. Diazoxide (50 micromol/L), a selective opener of the mitochondrial K(ATP) channel, decreased the LDH release of the myocytes subjected to hypoxia and reoxygenation, which could be abolished by pretreatment with NAC (1 mmol/L) or 5-HD (100 micromol/L). These results suggest that oxygen radical signals and mitochondrial K(ATP) channels are involved in the cardioprotection induced by TNF-alpha.