Oxidation of thioredoxin reductase in HeLa cells stimulated with tumor necrosis factor-α

Stimulation of cells with tumor necrosis factor-alpha (TNF-alpha) results in the increase in generation of H2O2 in mitochondria that leads to apoptosis. The effect of H2O2 produced by TNF-alpha on the redox status of selenocysteine (SeCys) residue essential for mitochondrial thioredoxin reductase (TrxR2) was investigated in HeLa cells. TNF-alpha caused accumulation of oxidized TrxR2 with a thioselenide bond. The conditional induction of SeCys-deficient TrxR2 resulted in the increased production of H2O2 and apoptosis. These results suggest that the SeCys residue of TrxR2 plays a critical role in cell survival by serving as an electron donor for Trx-II and subsequent peroxiredoxin-III, which is a primary line of defense against H2O2 in mitochondria. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.