Mammalian antioxidant Defenses are not inducible by H2O2

As an approach to understanding how mammals regulate H2O2 intracellular concentration to prevent its toxicity, we analyzed the genome-wide mRNA profile changes of human cells after treatment with a non-toxic H2O2 concentration. We identified a large and essentially late H2O2 response of induced and repressed genes that unexpectedly comprise few or no antioxidants but mostly apoptosis and cell cycle control activities. The requirement of the p53 regulator for regulating about a third of this H2O2 stimulon and the lack of an associated enhancement of total cellular H2O2 scavenging activity further suggest that H2O2 elicits a stress antiproliferative/ repair response that does not increase antioxidant defenses. We conclude that mammalian antioxidant defenses are constitutive, a finding that contrasts with the oxidant-inducibility of such defenses in microorganisms. This finding might be important in understanding the role of H2O2 as a key signaling molecule in mammals.