Oxidation of thioredoxin reductase in HeLa cells stimulated with tumor necrosis factor-alpha.
Stimulation of cells with tumor necrosis factor-alpha (TNF-alpha) results in the increase in generation of H(2)O(2) in mitochondria that leads to apoptosis. The effect of H(2)O(2) 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 H(2)O(2) 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 H(2)O(2) in mitochondria.
Kim
Jae-Ryong
JR
Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
Lee
Seon-Min
SM
Cho
Seung-Hyun
SH
Kim
Jung-Hyun
JH
Kim
Byung-Hak
BH
Kwon
Jaeyul
J
Choi
Cheol Yong
CY
Kim
Yeong-Dae
YD
Lee
Seung-Rock
SR
D000818:Animals; D017209:Apoptosis; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D053938:DNA Fragmentation; D004220:Disulfides / Q000737:chemistry; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology; D009154:Mutation; D009249:NADP / Q000737:chemistry; D010084:Oxidation-Reduction; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017279:Selenocysteine / Q000737:chemistry / Q000378:metabolism; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004220:Disulfides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D017279:Selenocysteine; D009249:NADP; D006861:Hydrogen Peroxide; C516124:TXNRD1 protein, human; C516127:TXNRD2 protein, human; D054481:Thioredoxin Reductase 1; D054482:Thioredoxin Reductase 2; D013880:Thioredoxin-Disulfide Reductase; C516126:Txnrd1 protein, rat; C516129:Txnrd2 protein, rat; D003545:Cysteine