Studies on Induction and Functions of Thioredoxin Reductase in Stress Responses

硫氧还蛋白还原酶应激反应的诱导及功能研究

• 批准号: 13672345
• 负责人: HARA Shuntaro
• 金额: $ 2.24万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672345/
• 关键词: Thiorecoxin reductase; Transcription factor; Redox; NF-κB; Stress response; Cadmium; レドックス制御; ストレス応答

Thioredoxin reductase (TrxR) is an antioxidant enzyme that has an ability to reduce thioredoxin (Trx). It is indicated that Trx plays an important role in stress responses, but the role of TrxR in the stress responses remains unclear. To date, three TrxR isozymes, TrxR1, TrxR2 and Trx3, have been identified. Among these isozymes, only TrxR1 is induced by various kinds of stresses. In this study, in order to reveal the role of TrxR in stress responses, the mechanism of induction and the functions of TrxR1 were studied as follows:(1) Regulation of stress-induced TrxR1 expression - Exposure of bovine arterial endothelial cells (BAEC) to TNFα, PMA+A23187, or Cd upregulated the expression of TrxR1 but neither TrxR2 nor TrxR3. First, role of the promoter region in the huma TrxR1 gene was evaluated by the transient transfection of luciferase reporter vectors into BAEC. Both PMA+A23187 and Cd elevated luciferase activity via the region between-646 and 46 bp. On the other hand, TNFα did not affect the luciferase activity, but the mRNA decay experiments using actinomycin D showed that TNFα stabilized TrxR1 mRNA. These results indicate that both transcriptional activation and posttranscriptional mRNA stabilization may contribute to the stress-induced expression of TrxR1, and that the contributive mechanisms may vary with kinds of stresses.(2) Role of TrxR1 in stress-responsive transcription factor-mediated gene expression - Reporter gene analysis revealed that the overexpression of TrxR1 enhanced AP-1- and NF-κB-dependent gene expression. The catalytic selenocysteine residue of TrxR1, which is essential for reducing Trx, was required for this activation, and aurothiomalate, an inhibitor of TrxR, suppressed this activation. These results suggest that TrxR1 may act as a positive regulator of stress-responsive transcription factors, AP-1 and NF-κB via its ability to reduce Trx.

硫代氧蛋白还原酶（TRXR）是抗氧化酶以减少硫氧化氧化物（TRX），但TRXR在应力响应中的作用仍然不清楚。通过各种应力诱导。 （BAEC）187或CD上的表达既不是TRXR2和TRXR3，首先，启动子区域的作用是通过Luciferase Leporter vectors的瞬态来评估的。另一方面，TNFα不影响您的荧光素酶活性，mRNA衰变实验D显示了TNFα稳定的TRXR1 mRNA。在TRXR1上增强了AP-1和NF-κB-Depepent基因的表达。 -κB通过其减少TRX的能力。