Overexpression of thioredoxin reductase 1 regulates NF-κB activation

✍ Scribed by Atsuko Sakurai; Kouji Yuasa; Yasuko Shoji; Seiichiro Himeno; Masafumi Tsujimoto; Manabu Kunimoto; Nobumasa Imura; Shuntaro Hara

• Book ID: 102310792
• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 315 KB
• Volume: 198
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.10377

✦ Synopsis

Abstract

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‐κB. 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‐α (TNFα) in vascular endothelial cells. Furthermore, the overexpression of TrxR1 enhanced TNFα‐induced DNA‐binding activity of NF‐κB and NF‐κB‐dependent gene expression. The catalytic Sec residue of TrxR1, which is essential for reducing Trx, was required for this NF‐κB activation, and aurothiomalate, an inhibitor of TrxR, suppressed TNFα‐induced activation of NF‐κB and the expression of NF‐κB‐targeted proinflammatory genes such as E‐selectin and cyclooxygenase‐2. These results suggest that TrxR1 may act as a positive regulator of NF‐κB and may play an important role in the cellular inflammatory response. © J. Cell. Physiol. 198: 22–30, 2004© 2003 Wiley‐Liss, Inc.