On the antioxidant mechanisms of Bcl-2: a retrospective of NF-kappaB signaling and oxidative stress.
Antioxidant and prooxidant signaling pathways are emanating as major players in, and regulators of, cell death and apoptosis. Redox conception of the critical role of oxidative stress in determining cell fate is being established-a foundation that craves deeper than the basic understanding of physiochemical interactions to extend beyond that into the realms of deciphering the molecular codes implicated with apoptosis. The proto-oncogene Bcl-2 is no stranger being a major player and decoder in controlling apoptosis, ostensibly via the regulation of redox equilibrium and disequilibrium. One of those potential mechanisms exhibited by Bcl-2 is its ability to counteract the detrimental effects of cell damage caused by free radicals, thereby gaining its well-known property of being an antioxidant. But the question is: what are the molecular mechanisms involved with the antioxidant role of Bcl-2 in the face of cell damage and apoptosis? Currently, a stance is being upheld in that the Bcl-2 antioxidant efficacy should be weighed against its ability to manipulate transcriptional control, through the regulation of specific transcription factors. NF-kappaB is no doubt one of the best candidates when it comes to the arena of oxidative stress, inflammation, and apoptosis. Therein, current themes in the burgeoning antioxidant role of Bcl-2 are exposed within the context of transcriptional control of NF-kappaB, thereby holding potential avenues for alleviating therapeutic approaches in the regulation of apoptosis.
Haddad
John J
JJ
Severinghaus-Radiometer Research Laboratories, University of California, San Francisco, CA, USA. johnjhaddad@yahoo.co.uk
D000975:Antioxidants / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D009336:Necrosis; D018384:Oxidative Stress / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D000975:Antioxidants; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2