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

Abstract
Stimulation of cells with tumor necrosis factor‐α (TNF‐α) results in the increase in generation of H2O2 in mitochondria that leads to apoptosis. The effect of H2O2 produced by TNF‐α on the redox status of selenocysteine (SeCys) residue essential for mitochondrial thioredoxin reductase (TrxR2) was investigated in HeLa cells. TNF‐α 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.