Grant-in-Aid for Scientific Research (A)
|Allocation Type||Single-year Grants|
|Research Institution||KYOTO UNIVERSITY|
YODOI Junji Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (80108993)
WADA Hiromi Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (90167205)
MATSUMORI Akira Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (70135573)
KUMAGAI Shunichi Kobe University, School of Medicine, Professor, 医学部, 教授 (00153346)
HIROTA Kiichi Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (00283606)
INAMOTO Takashi Kyoto University, College of Medical Technology, Professor, 医療技術短期大学部, 教授 (10135577)
|Project Period (FY)
1997 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥28,000,000 (Direct Cost : ¥28,000,000)
Fiscal Year 1999 : ¥5,400,000 (Direct Cost : ¥5,400,000)
Fiscal Year 1998 : ¥7,200,000 (Direct Cost : ¥7,200,000)
Fiscal Year 1997 : ¥15,400,000 (Direct Cost : ¥15,400,000)
|Keywords||thioredoxin / redox / oxidative stress / ELISA / transgenic mouse / ADF|
Human thioredoxin (TRX) is induced by a variety of oxidative stress. It has multiple functions such as anti-oxidant activity, regulation of transcription factors, and cytokine or chemokine-like activities. In this study, we measured serum/plasma TRX levels using ELISA to evaluate their relation to oxidative stress.
1. Plasma levels of TRX were elevated in HIV-infected patients and correlated with decreases of intracellular glutathione levels in lymphocytes and changes of lymphocyte surface markers. The prognosis of patients with elevated plasma TRX was poor.
2. Serum TRX levels in HCV-infected patients were significantly higher than in normal individuals. Serum TRX levels correlated with the disease progression of hepatitis and serum ferritin levels. Patients with higher serum TRX levels exhibited resistance to IFN therapy.
3. Serum levels of TRX were elvated in patients with autoimmune diseases, such as SLE, rheumatoid arthritis (RA) and Sjogren's syndrome. TRX levels in knee synovial fl
uid of patients with RA correlated with serum CRP levels, and were higher than that in patients with other arthritis such as arthritis deformans.
4. During open heart surgery with cardiopulmonary bypass, plasma TRX levels were elevated after reperfusion of the postcardioplegic heart.
5. TRX expression in rat hearts increased 24 hours after transient coronary artery occlusion. Administration of recombinant human TRX decreased the activation of NF-κB and ischemia/reperfusion injury.
6. After middle cerebral artery occlusion, TRX expression in rats decreased in the ischemic core regions, but increased in the perifocal ischemic regions. The infarct areas and volume were significantly smaller in TRX trangenic mice than in control mice.
Thus, our results suggest that TRX levels reflect oxidative stress and the measurement of TRX would give us insights into pathogenesis of oxidative stress-associated disorders. Moreover, administration of TRX may be useful for preventing oxidative stress and cure for its associated diseases. Less