Mammalian antioxidant defenses are not inducible by H2O2.
As an approach to understanding how mammals regulate H(2)O(2) toxicity, intracellular concentration to prevent its we analyzed the genome-wide mRNA profile changes of human cells after treatment with a non-toxic H(2)O(2) concentration. We identified a large and essentially late H(2)O(2) 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 H(2)O(2) stimulon and the lack of an associated enhancement of total cellular H(2)O(2) scavenging activity further suggest that H(2)O(2) 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 H(2)O(2) as a key signaling molecule in mammals.
Desaint
Stéphane
S
Laboratoire Stress Oxydants et Cancer, Service de Biologie Moléculaire Systémique, Départment de Biologie Joliot-Curie, Commissariat à l'Energie Atomique/Saclay, Gif-sur-Yvette Cedex, France.
Luriau
Stéphanie
S
Aude
Jean-Christophe
JC
Rousselet
Germain
G
Toledano
Michel B
MB
D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000975:Antioxidants; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide