[Oxidative stress and gene expression].
Oxidative stress elicits cellular toxicity implicating various targets such as DNA, RNA, proteins, lipids.... Similarly to other stress conditions, it triggers cellular adaptation and the induction of defense mechanisms. Adaptation to this stress is ubiquitous but it displays cell specificity. Adaptation to stress requires the regulation of a large number of genes. Those encoding anti-oxidant and repair genes are induced while others are repressed. The activity of several transcription factors is altered by oxidative stress. Many transcription factors are inhibited because of the oxidation of cysteine residues in their DNA binding domains. In the case of NFI, a cysteine in the transactivating domain is oxidized which leads to inactivation. The mechanisms of transcription factor activation are often complex, as in the case of cJun. This factor is activated by a kinase signalling cascade. Paradoxically, it is also inhibited by stress since one of its cysteines is oxidized; however, this oxidation is repaired in the nucleus by the ref1-thioredoxine system. A similar mechanism is observed for NF kappa B. Alteration of the redox status is observed in several physiological pathological and toxic conditions. It is also provoked by other cellular stress, in particular endoplasmic reticulum stress, hypoxia, shear stress, osmotic and heat shocks. The actual role of oxidative stress during other stress conditions remains to be elucidated. This widespread implication of oxidative stress could account for its role in a variety of disease such as neurodegenerative diseases, cancer, atherosclerosis, and diabetes. The efficacy of anti-oxidant therapy depends on the actual contribution of oxidative stress to these diseases.
Barouki
R
R
INSERM U490, Centre Universitaire des Saints Pères, Université René Descartes, 75270 Paris.
Morel
Y
Y
D000818:Animals; D001665:Binding Sites; D003545:Cysteine / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism
D014157:Transcription Factors; D004247:DNA; D003545:Cysteine
Stress oxydant et expression des gènes.