Tumor necrosis factor alpha induced apoptosis in human neuronal cells: protection by the antioxidant N acetylcysteine and the genes bcl 2 and crmA

Abstract

Tumor necrosis factor alpha (TNF alpha) is a candidate human immunodeficiency virus type 1 induced neurotoxin that contributes to the pathogenesis of AIDS dementia complex. We report here on the effects of exogenous TNF alpha on SK N MC human neuroblastoma cells differentiated to a neuronal phenotype with retinoic acid, TNF alpha caused a dose dependent loss of viability and a corresponding increase in apoptosis in differentiated SK N MC cells but not in undifferentiated cultures. Importantly, intracellular signalling via TNF receptors, as measured by activation of the transcription factor NF kappa B, was unaltered by retinoic acid treatment. Finally, overexpression of bcl 2 or crmA conferred resistance to apoptosis mediated by TNF alpha, as did the addition of the antioxidant N acetylcysteine. These results suggest that TNF alpha induces apoptosis in neuronal cells by a pathway that involves formation of reactive oxygen intermediates and which can be blocked by specific genetic interventions.