Tumor Necrosis Factor Alpha-Induced Apoptosis in Human Neuronal Cells: Protection by the Antioxidant N-Acetylcysteine and the Genes bcl-2 and crmA

Authors

Angela K. Talley, University of Rochester Medical Center
Stephen Dewhurst, University of Rochester Medical Center
Seth W. Perry, University of Rochester Medical Center
Sheila C. Dollard, University of Rochester Medical Center
Suryaram Gummuluru, University of Rochester Medical Center
Steven M. Fine, University of Rochester Medical Center
Deborah New, University of Rochester Medical Center
Leon Epstein, University of Rochester Medical Center
Howard Gendelman, University of Nebraska Medical Center & Nebraska Center for VirologyFollow
Harris A. Gelbard, University of Rochester Medical Center

Date of this Version

May 1995

Comments

Published in MOLECULAR AND CELLULAR BIOLOGY, May 1995, p. 2359–2366 Vol. 15, No. 5. 0270-7306/95/$04.0010 Copyright © 1995, American Society for Microbiology. Used by permission.

Abstract

Tumor necrosis factor alpha (TNF-α) 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-α on SK-N-MC human neuroblastoma cells differentiated to a neuronal phenotype with retinoic acid. TNF-α 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-kB, was unaltered by retinoic acid treatment. Finally, overexpression of bcl-2 or crmA conferred resistance to apoptosis mediated by TNF-α, as did the addition of the antioxidant N-acetylcysteine. These results suggest that TNF-a induces apoptosis in neuronal cells by a pathway that involves formation of reactive oxygen intermediates and which can be blocked by specific genetic interventions.