Tumor Necrosis Factor Alpha-induced Apoptosis in Human Neuronal Cells: Protection by the Antioxidant N-acetylcysteine and the Genes Bcl-2 and CrmA

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1995 May 1

PMID 7739519

Citations 55

Authors

A K Talley

S Dewhurst

S W Perry

S C Dollard

S Gummuluru

S M Fine

D New

L G Epstein

H E Gendelman

H A Gelbard

Affiliations

Soon will be listed here.

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.

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