2000 Fiscal Year Final Research Report Summary
The mechanism of Ca2+ ion inflow regulated by KF506 binding proteins (FKBP) and Calcineurin.
| Project/Area Number |
11480246
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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 |
神経・脳内生理学
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
MATSUI Hideki Medical School, OKAYAMA UNIVERSITY, Professor, 医学部, 教授 (30157234)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIZAWA Kazuhito Medical School, OKAYAMA UNIVERSITY, Lecturer, 医学部, 講師 (40274287)
MORIWAKI Akiyoshi Medical School, OKAYAMA UNIVERSITY, Lecturer, 医学部, 講師 (10144742)
MATSUSHITA Masayuki Medical School, OKAYAMA UNIVERSITY, Assistant, 医学部, 助手 (30273965)
RI Syouten Medical School, OKAYAMA UNIVERSITY, Assistant, 医学部, 助手 (90325093)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Calcineurin / Ca channel / Neuronal cell death / Immunosuppressant / FKBP / Cyclosporin / Urinary bladder hypertrophy / FK506 |
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| Research Abstract |
We investigated the mechanism of Ca2+ ion inflow into neurons and muscle cells regulated by FKBPs (FK506 binding proteins) and Calcineurin. We further investigated Pathophysiological mechanism of Ca2+ inflow in animal model of diseases. Established and primary cultured cell systems and a rat hypertrophic urinary bladder model were used for this investigations. In intensive research for two years supported by this grant, we have got results as follows,
1) We established primary culture of fetal rat hippocampal neurons and induced excitatory neuronal cell death by glutamate and NMDA.
2) We showed that calcineurin inhibitors, FK506 and Cyclosporin A inhibited the excitatory neuronal cell death but not Rapamycin.
3) In the excitatory neuronal cell death, the Ca2+ ion inflow and the successive activation of calcineurin is essentially important as prerequisites for the induction of neuron death.
4) The activated calcineurin induced translocation of a transcription factor, NF-AT from cytoplasm to nuclear compartment of neurons.
In a hypertrophic urinary bladder model,
1) We showed the increment of actin and myosin expression and the change of calcineurin expression during hypertrophy induction.
2) Calcineurin inhibitor, FK506 inhibited bladder hypertrophy.
3) Hypertrophic bladder smooth muscle cells showed increased Ca2+ ion inflow through ATP dependent Ca channels.
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