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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Acetylcysteine / pharmacology
-
Animals
-
Antioxidants
-
Apoptosis / physiology*
-
Base Sequence
-
Cell Compartmentation
-
Cell Line
-
Cell Survival
-
Cyanides / pharmacology
-
Free Radicals
-
Glucocorticoids / deficiency
-
Glutathione Peroxidase / metabolism
-
Humans
-
Interleukin-3 / deficiency
-
Lipid Peroxidation / physiology*
-
Mice
-
Molecular Sequence Data
-
Oxygen / metabolism*
-
Oxygen Consumption
-
Proto-Oncogene Proteins / isolation & purification
-
Proto-Oncogene Proteins / physiology*
-
Proto-Oncogene Proteins c-bcl-2
-
Recombinant Proteins / biosynthesis
-
Respiratory Burst / drug effects
-
Superoxide Dismutase / metabolism
-
Superoxides / metabolism
-
Vitamin K / pharmacology
Substances
-
Antioxidants
-
Cyanides
-
Free Radicals
-
Glucocorticoids
-
Interleukin-3
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-bcl-2
-
Recombinant Proteins
-
Superoxides
-
Vitamin K
-
Glutathione Peroxidase
-
Superoxide Dismutase
-
Oxygen
-
Acetylcysteine