| Co-Investigator(Kenkyū-buntansha) |
AIHARA Noritaka NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, INSTRUCTOR, 医学部, 助手 (00264739)
YAMADA Kazuo NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, PROFESSOR, 医学部, 教授 (90150341)
MASAGO Atsuo NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, INSTRUCTOR, 医学部, 助手 (70209419)
KATO Taiji NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, PROFESSOR, 医学部, 教授 (60094364)
IWATA Akira NAGOYA CITY UNIVERSITY, MEDICAL SCHOOL, INSTRUCTOR, 医学部, 助手 (90275131)
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| Research Abstract |
Calcineurin, serin/threonine phosphatase, has an important role for the differentiation/growth of immune cells and pathology of immune diseases because it acitvates T-cell. FK-506 (tacrolimus), a new immunosuppressant, contributes to success in organ transplantation. The immunosuppressing mechanism of FK-506 is known to be an inhibition of calcineurin activity by complex formation of calcineurin and FK-506 with immunophilin. Calcineurin widely distributes in hippocampus, striatum, and cerebral cortex. FK-506 has neuroprotective effects against glutamate toxicity, focal, and transient global cerebral ischemia. Marked apoptosis occurred in calcineurin activated gene transfected cells under serum-free conduction, which is inhibited by direct combination with Bcl-2. We suspected that calcineurin had some roles on apoptosis in various cerebral damages. In the present study, we clarified changes of expression of immediate early genes (c-fos, c-jun) and apoptosis related gene in some conditions, increased intracranial pressure, impact injury, and cryogenic injury. Then, we produced diffuse axonal injury model using rats, and analyzed changes of IEGs, apoptosis related genes, and amyloid precursor protein (APP) expression after calcineurin administration. However, we could not obtain significant changes of these parameters.
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