Reactive Oxygen Species-independent Oxidation of Thioredoxin in Hypoxia: INACTIVATION OF RIBONUCLEOTIDE REDUCTASE AND REDOX-MEDIATED CHECKPOINT CONTROL*
AUTOR(ES)
Muniyappa, Harish
FONTE
American Society for Biochemistry and Molecular Biology
RESUMO
We have investigated the role of cellular redox state on the regulation of cell cycle in hypoxia and shown that whereas cells expressing mutant thioredoxin (Trx) or a normal level of Trx undergo increased apoptosis, cells overexpressing Trx are protected against apoptosis. We show that hypoxia activates p53 and Chk1/Chk2 proteins in cells expressing normal or mutant Trx but not in cells overexpressing Trx. We also show that the activity of ribonucleotide reductase decreases in hypoxia in cells expressing redox-inactive Trx. Although hypoxia has been shown to induce reactive oxygen species (ROS) generation in the mitochondria resulting in enhanced p53 expression, our data demonstrate that hypoxia-induced p53 expression and phosphorylation are independent of ROS. Furthermore, hypoxia induces oxidation of Trx, and this oxidation is potentiated in the presence of 6-aminonicotinamide, an inhibitor of glucose-6-phosphate dehydrogenase. Taken together our study shows that Trx redox state is modulated in hypoxia independent of ROS and is a critical determinant of cell cycle regulation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2719345Documentos Relacionados
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