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

3127 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Vitamin K 3
Peroxides
Cyanides
Lipid Peroxidation
Free Radicals
Antioxidants
Apoptosis
Lipids
Mitochondria
Respiratory Burst
Nuclear Envelope
Acetylcysteine
Cell death
Glutathione Peroxidase
Endoplasmic Reticulum
Superoxide Dismutase
Reactive Oxygen Species
Respiration
Cell Death
Oxygen

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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

Bcl-2 functions in an antioxidant pathway to prevent apoptosis. / Hockenbery, David M.; Oltvai, Zoltan N.; Yin, Xiao-Ming; Milliman, Curt L.; Korsmeyer, Stanley J.

In: Cell, Vol. 75, No. 2, 22.10.1993, p. 241-251.

Research output: Contribution to journalArticle

Hockenbery, DM, Oltvai, ZN, Yin, X-M, Milliman, CL & Korsmeyer, SJ 1993, 'Bcl-2 functions in an antioxidant pathway to prevent apoptosis', Cell, vol. 75, no. 2, pp. 241-251. https://doi.org/10.1016/0092-8674(93)80066-N
Hockenbery DM, Oltvai ZN, Yin X-M, Milliman CL, Korsmeyer SJ. Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell. 1993 Oct 22;75(2):241-251. https://doi.org/10.1016/0092-8674(93)80066-N
Hockenbery, David M. ; Oltvai, Zoltan N. ; Yin, Xiao-Ming ; Milliman, Curt L. ; Korsmeyer, Stanley J. / Bcl-2 functions in an antioxidant pathway to prevent apoptosis. In: Cell. 1993 ; Vol. 75, No. 2. pp. 241-251.
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