Bcl-2 functions in an antioxidant pathway to prevent apoptosis

DM Hockenbery, ZN Oltvai, XM Yin, CL Milliman… - Cell, 1993 - cell.com
DM Hockenbery, ZN Oltvai, XM Yin, CL Milliman, SJ Korsmeyer
Cell, 1993cell.com
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 HzO2-and menadione-
induced oxidative deaths. Bcl-2 did not prevent the cyanide-resistant oxidative burst …
Summary
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 HzO2-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.
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