期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 284, 期 25, 页码 17069-17081出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M109.008557
关键词
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资金
- National Institutes of Health [R01 HL071558]
- University of Arkansas for Medical Science Research Council
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.
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