2003 Fiscal Year Final Research Report Summary
ANALYSIS OF MOLECULAR MECHANISMS WHEREBY THIOREDOXIN TRASNGENIC MICE ARE RESISTANT TO INFLAMMATION AND STRESS
| Project/Area Number |
14370074
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
NAKAMURA Hajime GRADUATE SCHOOL OF MEDICINE, KYOTO UNIVERISTY, ASSOCIATE PROFESSOR, 医学研究科, 助教授 (70303914)
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| Co-Investigator(Kenkyū-buntansha) |
YODOI Junji INSTITUTE FOR VIRUS RESEARCH, KYOTO UNVERSITY, PROFESSOR, ウイルス研究所, 教授 (80108993)
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| Project Period (FY) |
2002 – 2003
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| Keywords | THIOREDOXIN / TRANSGENIC MICE / REDOX / STRESS / INFLAMMATION / HOST DEFENSE / HEPATITIS / ACUTELUNG INJURY |
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| Research Abstract |
THIOREDOXIN (TRX) IS A SMALL PROTEIN WITH A REDOX ACTIVE DITHIOL/DISULFIDE IN ITS ACTIVE SITE SEQUENCE: -CYS-GLY PRO-CYS-. TRX IS INDUCED BY A VARIETY OF OXIDATIVE STRESS AND SECRETED FROM CELLS. TRX-TRANSGENIC (TRX TG) MICE ARE MORE RESISTANT TO STRESSES INDUCED BY ISCHEMIA-REPERFUSION AND ULTRAVIOLET IRRADATION AND SURVIVE LONGER THAN WILD TYPE MICE. BLEOMYCIN-INDUCED LEUKOCYTE INFILTRATION INTO THE, LUNG INTERSTITIAL SPACE WAS DRAMTICALLY SUPPRESSED IN TRX TG MICE. ACUTE HEPATIC INJURY CAUSED BY THIOACETAMIDE WAS ALSO SUPPRESSED IN TRX TG MICE. MOREOVER, ADMINISTRATION OF RECOMBINANT THIOREDOXIN PROTEIN ALSO SUPPRESSED THE EXTRAVASATION OF LEUKOCYTES, THE INTRACELLULAR GENERATION OF REACTIVE OXYGEN SPECIES AND CELLULAR APOPTOSIS. THESE RESULTS SUGGEST THE THERAPEUTIC POTENTIAL OF RECOMBINANT THIOREDOXIN FOR STRESS-ASSOCIATED DISORDERS.
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