By Chandan K. Sen, Lester Packer, Patrick A. Baeuerle
This quantity addresses oxidant-reduction or redox and antioxidant delicate molecular mechanisms and the way they're implicated in numerous sickness strategies. attainable ideas to pharmacologically and/or nutritionally manage such redox-sensitive molecular responses are emphasised. Key Features:* Reactive species as intracellular messengers* Redox rules of mobile responses* medical implications of redox signaling and antioxidant treatment
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Surprisingly, few of these induced mRNAs involve the "classical" antioxidant enzymes superoxide dismutase, catalase, or glutathione peroxidase. , 1990). In mammalian cells, modest inductions at best have been observed for antioxidant enzyme mRNAs and, in most cases, no modulation observed at all. This weak response led to a general impression that oxidative stress was probably unimportant in the modulation of mammalian gene expression. Several subsequent studies, however, changed this perception.
1991) Shull et al. (1991) Stevens and Autor (1977) Stralin and Marklund (1994) Polyak et al. (1997) Kim et al. (1997) in the mammalian genome. , 1992). Therefore, reactive oxygen species must be important mediators of mammalian gene expression. A second important study in the field was performed by Keyse and Tyrrell (1989). These investigators observed that the protein and mRNA to heme oxygenase is strongly induced by oxidative stress, also using a mammalian cell culture model system. The induction of heme oxygenase has now been observed in many model systems using a number of different inductants, so much so that heme oxygenase has become the prototype 26 Oana R.
One of the more impressive demonstrations of the modulation of gene expression via an intracellular-generated oxidative stress, and one with important physiological ramifications, was reported by Polyak et al. (1997). In this study, the genes that mediate the apoptogenic effects of p53 overexpression were examined, p53 is inactivated in a large percentage of human cancers, and its overexpression mediates cellular growth arrest and apoptosis. Using a model system in which overexpression of p53 led to apoptosis, 14 genes were found to be strongly induced as analyzed using the technique of SAGE.
Antioxidant and Redox Regulation of Genes by Chandan K. Sen, Lester Packer, Patrick A. Baeuerle