Potentiation of cellular antioxidant capacity by Bcl-2: implications for its antiapoptotic function.
A substantial body of data from clinical and laboratory studies indicates that reactive oxygen intermediates are implicated in the pathogenesis of diverse human diseases, including cancer, diabetes, and neurodegenerative disorders. Oxidative stress induced by reactive oxygen intermediates often causes cell death via apoptosis that is regulated by a plenty of functional genes and their protein products. Bcl-2, which is an integral intermitochondrial membrane protein, blocks apoptosis induced by a wide array of death signals. In spite of extensive research, the molecular milieu that characterizes the antiapoptotic function of Bcl-2 is complex and not fully identified. Recently, there are several lines of evidence that Bcl-2 functions via antioxidant pathways to prevent apoptosis. Thus, bcl-2-overexpressing cells exhibit elevated expression of antioxidant enzymes and higher levels of cellular GSH compared with the control cells transfected with the vector alone. There has been increasing evidence supporting that the redox-sensitive transcription factor nuclear factor kappaB regulates the activity and/or expression of antioxidative and antiapoptotic target genes and promotes cell survival against oxidative cell death. This commentary focuses on the antioxidative functions of Bcl-2 and underlying molecular mechanisms in relation to its antiapoptotic property. The role of Bcl-2 in regulation of nuclear factor kappaB signaling pathways and possible cross-talk with mitogen-activated protein kinases are also discussed.
Jang
Jung-Hee
JH
Laboratory of Biochemistry and Molecular Toxicology, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea.
Surh
Young-Joon
YJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015854:Up-Regulation
D000975:Antioxidants; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D020928:Mitogen-Activated Protein Kinases