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

Angela K. Talley, Stephen Dewhurst, Seth W. Perry, Sheila C. Dollard, Suryaram Gummuluru, Steven M. Fine, Deborah New, Leon G. Epstein, Howard E. Gendelman, Harris A. Gelbard

Research output: Contribution to journalArticle

273 Scopus citations

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-κB, 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- α induces apoptosis in neuronal cells by a pathway that involves formation of reactive oxygen intermediates and which can be blocked by specific genetic interventions.

Original languageEnglish (US)
Pages (from-to)2359-2366
Number of pages8
JournalMolecular and cellular biology
Volume15
Issue number5
DOIs
StatePublished - May 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Talley, A. K., Dewhurst, S., Perry, S. W., Dollard, S. C., Gummuluru, S., Fine, S. M., New, D., Epstein, L. G., Gendelman, H. E., & Gelbard, H. A. (1995). Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: Protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crmA. Molecular and cellular biology, 15(5), 2359-2366. https://doi.org/10.1128/MCB.15.5.2359