Radical ideas: genetic responses to oxidative stress.

1. Complex genetic systems counteract different types of 'oxidative stress' caused by reactive derivatives of oxygen. 2. The bacterial oxyR system responds to peroxide stress and is governed by OxyR, a transcription factor activated by the formation of an intramolecular disulphide bond in H2O2-treated cells. Activated OxyR switches on several genes encoding antioxidant functions, such as catalase. During aerobic growth, oxyR acts homeostatically to regulate cellular H2O2 levels. 3. The bacterial soxRS system responds to superoxide or nitric oxide (NO) stress and is activated in two transcriptional stages. The SoxR protein is activated by oxidation of its [2Fe-2S] centres in cells exposed to superoxide-generating agents, such as paraquat, or to No. Activated SoxR stimulates the soxS gene and SoxS protein then induces at least 15 genes encoding antioxidant functions, such as superoxide dismutase, metabolic functions, such as fumarase, and antibiotic resistance by activation of efflux pumps. The soxRS system may function in resistance to NO-generating immune cells and may contribute to clinical antibiotic resistance. 4. Human cells respond to subtoxic levels of NO by inducing 12 proteins and down-regulating others. A key induced activity is haem oxygenase 1, which is controlled post-transcriptionally. 5. Motor neurons exhibit adaptive resistance to NO, triggered by exposure to subtoxic NO levels, and providing resistance to usually cytotoxic levels of this agent or H2O2. Adaptive resistance to NO depends strongly on the inducible heam oxygenase activity.