Reactive oxygen species induce cardiomyocyte apoptosis partly through TNF-α

Many studies have indicated that oxidative stress induces apoptosis in cardiomyocytes, but its mechanism remains unknown. We examined whether tumor necrosis factor-alpha (TNF-alpha) is involved in oxidative stress-induced cardiomyocyte apoptosis. Pretreatment with anti-TNF-alpha antibody significantly decreased the number of H2O2-induced TUNEL-positive cardiomyocytes. Expression of TNF-alpha gene was upregulated by H2O2, and H2O2 mildly but significantly increased the concentration of TNF-a in the culture medium. Although neither low dose of H2O2 nor TNF-alpha induced apoptosis, stimulation with H2O2 and TNF-alpha synergistically increased apoptosis. These results suggest that oxidative stress induces apoptosis of cardiac myocytes partly through TNF-alpha. (C) 2002 Elsevier Science Ltd. All rights reserved.