| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Hajime INSTITUTE FOR VIRUS RESEARCH,KYOTO UNIVERSITY, ASSISTANT PROFESSOR, ウィルス研究所, 助手 (70303914)
MASUTANI Hiroshi INSTITUTE FOR VIRUS RESEARCH,KYOTO UNIVERSITY, ASSISTANT PROFESSOR, ウィルス研究所, 助手 (50252523)
IWATA Shogo Tazuke Kofukai Medical Institute III, Staff Scientist, 第3部研究部, 研究員 (80291904)
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| Research Abstract |
To analyze the influences on the host defense system of surgical stresses such as operative procedures or administration of anti-cancer agents, redox regulating factors such as glutathione and thioredoxin (TRX) and mitochondrial functions such as ATP production and cytochrome c release were monitored as key indicators of host defense mechanism via redox regulation and considered for possible clinical applications.
1) We analyzed plasma thioredoxin (TRX) and glutaredoxin levels during surgical stress such as operative procedures. During open heart surgery with cardiopulmonary bypass, plasma TRX levels were elevated, whereas plasma glutaredoxin levels were not significantly changed. Especially oxidized TRX are elevated after ischemia-reperfusion (Nakamura, et al. Free Radical Biol Med. 24 : 1176-1186, 1998). Plasma TRX measurements will be good indicators for monitoring surgical stress.
2) TRX reductase as well as TRX is possibly involved in cellular resistance to CDDP (Sasada, et al. Free
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Radical Biol. Med. in press). TRX is overexpressed in pancreatic cancers as well as in other gastrointestinal cancers (Nakamura, et al. Cancer Detection Prevention in press). Inhibition of the TRX system will be a new tool of cancer therapy.
3) Diamide induced cell apoptosis with release of cytochrome c from mitochondria and activation of caspase 3. Cellular thiol-dependent redox status is deeply involved in the signal transduction of apoptosis (Ueda, et al. J.Immunol. 161 : 6689-6695, 1998).
4) Glutathione levels and NK activities of liver-associated lymphocytes in thioacetamide-induced cirrhotic rats were suppressed compared with controls. They were improved by N-acetylcysteine, a glutathione precursor (Tsuyuki, et al. Int. Immunol. 10 : 1501-1508, 1998).
5) Creatine kinase transgenic mice, which maintained ATP production in mitochondria, were more resistant to D-galactosamine-induced hepatic injuries compared with controls (Kanazawa, et al. J.Surg. Res. 80 : 229-235, 1998). 4) and 5) suggest that maitanance of redox status in the liver plays a key role in the host defense system including NK activity. Less
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