[Reactive oxygen species and mitochondrial KATP-sensitive channels mediated cardioprotection induced by TNF-alpha during hypoxia and reoxygenation].
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.
Fu
Chen
C
Department of Physiology, Zhejiang University School of Medicine, Hangzhou 310031.
Cao
Chun-Mei
CM
Xia
Qiang
Q
Yang
Jun
J
Lu
Yuan
Y
D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D002478:Cells, Cultured; D006352:Heart Ventricles / Q000166:cytology; D054086:KATP Channels / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism* / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000166:cytology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D054086:KATP Channels; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen