Bcl-2 functions in an antioxidant pathway to prevent apoptosis

David M. Hockenbery, Zoltan N. Oltvai, Xiao Ming Yin, Curt L. Milliman, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

3189 Scopus citations

Abstract

Bcl-2 inhibits most types of apoptotic cell death, implying a common mechanism of lethality. Bcl-2 is localized to intracellular sites of oxygen free radical generation including mitochondria, endoplasmic reticula, and nuclear membranes. Antioxidants that scavenge peroxides, N-acetylcysteine and glutathione peroxidase, countered apoptotic death, while manganese superoxide dismutase did not. Bcl-2 protected cells from H2O2- and menadione-induced oxidative deaths. Bcl-2 did not prevent the cyanide-resistant oxidative burst generated by menadione. Two model systems of apoptosis showed no increment in cyanide-resistant respiration, and generation of endogenous peroxides continued at an inherent rate that was unaltered by Bcl-2. Following an apoptotic signal, cells sustained progressive lipid peroxidation. Overexpression of Bcl-2 functioned to suppress lipid peroxidation completely. We propose a model in which Bcl-2 regulates an antioxidant pathway at sites of free radical generation.

Original languageEnglish (US)
Pages (from-to)241-251
Number of pages11
JournalCell
Volume75
Issue number2
DOIs
StatePublished - Oct 22 1993

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hockenbery, D. M., Oltvai, Z. N., Yin, X. M., Milliman, C. L., & Korsmeyer, S. J. (1993). Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell, 75(2), 241-251. https://doi.org/10.1016/0092-8674(93)80066-N