PMID- 14584040 OWN - NLM STAT- MEDLINE DCOM- 20040120 LR - 20071115 IS - 0021-9541 (Print) IS - 0021-9541 (Linking) VI - 198 IP - 1 DP - 2004 Jan TI - Overexpression of thioredoxin reductase 1 regulates NF-kappa B activation. PG - 22-30 AB - Thioredoxin reductase (TrxR) is a flavoprotein that contains a C-terminal penultimate selenocysteine (Sec) and has an ability to reduce thioredoxin (Trx), which regulates the activity of NF-kappa B. To date, three TrxR isozymes, TrxR1, TrxR2, and TrxR3, have been identified. In the present study, we found that among these isozymes only TrxR1 was induced by tumor necrosis factor-alpha (TNF alpha) in vascular endothelial cells. Furthermore, the overexpression of TrxR1 enhanced TNF alpha-induced DNA-binding activity of NF-kappa B and NF-kappa B-dependent gene expression. The catalytic Sec residue of TrxR1, which is essential for reducing Trx, was required for this NF-kappa B activation, and aurothiomalate, an inhibitor of TrxR, suppressed TNF alpha-induced activation of NF-kappa B and the expression of NF-kappa B-targeted proinflammatory genes such as E-selectin and cyclooxygenase-2. These results suggest that TrxR1 may act as a positive regulator of NF-kappa B and may play an important role in the cellular inflammatory response. FAU - Sakurai, Atsuko AU - Sakurai A AD - Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. FAU - Yuasa, Kouji AU - Yuasa K FAU - Shoji, Yasuko AU - Shoji Y FAU - Himeno, Seiichiro AU - Himeno S FAU - Tsujimoto, Masafumi AU - Tsujimoto M FAU - Kunimoto, Manabu AU - Kunimoto M FAU - Imura, Nobumasa AU - Imura N FAU - Hara, Shuntaro AU - Hara S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Antirheumatic Agents) RN - 0 (Isoenzymes) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 12244-57-4 (Gold Sodium Thiomalate) RN - EC 1.8.1.9 (TXNRD1 protein, human) RN - EC 1.8.1.9 (Thioredoxin Reductase 1) RN - EC 1.8.1.9 (Thioredoxin-Disulfide Reductase) RN - EC 1.8.1.9 (Txnrd1 protein, mouse) SB - IM MH - Animals MH - Antirheumatic Agents/metabolism MH - Cattle MH - Cells, Cultured MH - Endothelium, Vascular/cytology/metabolism MH - Gene Expression Regulation MH - Gold Sodium Thiomalate/metabolism MH - Humans MH - Isoenzymes/genetics/*metabolism MH - Liver/metabolism MH - Mice MH - NF-kappa B/*metabolism MH - Thioredoxin Reductase 1 MH - Thioredoxin-Disulfide Reductase/genetics/*metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2003/10/30 05:00 MHDA- 2004/01/21 05:00 CRDT- 2003/10/30 05:00 PHST- 2003/10/30 05:00 [pubmed] PHST- 2004/01/21 05:00 [medline] PHST- 2003/10/30 05:00 [entrez] AID - 10.1002/jcp.10377 [doi] PST - ppublish SO - J Cell Physiol. 2004 Jan;198(1):22-30. doi: 10.1002/jcp.10377.