| Project/Area Number |
14370766
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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 |
Environmental pharmacy
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| Research Institution | Kitasato University School of Pharmaceutical Sciences |
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Principal Investigator |
KUNIMOTO Manabu Kitasato University School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (20142101)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Methyl mercury / Cerebellar neuron / Apoptosis / Molecular mechanism / Neurotoxicity / calpain / p35 / cdk5 / 細胞内カルシウム / カルパイン |
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| Research Abstract |
It has been shown that methylmercury-induced death of cerebellar granule neurons is apoptotic both in vitro and in vivo. To clarify the molecular mechanism for the induction of apoptosis in cerebellar neurons by methylmercury, several lines of experiments have been performed using rat cerebellar neurons in primary culture. Cerebellar neurons prepared from neonatal rats were exposed to methylmercury at very low concentrations (up to 30nM) in vitro and possible involvement of calpain/p35/cdk5 cascade in the death process was examined, since the cascade is shown to be activated during the neuronal death in Alzheimer's disease. An activation of calpain was confirmed using a-fodrin as an intrinsic substrate in methylmercury-treated cerebellar neurons, in addition to the increased cleavage of p35 to p25 and the elevation of intracellular calcium level. While the cleavage of a-fodrin was almost completely inhibited by the addition of calpain inhibitor II, the processing of p35 to p25 was only slightly affected. Furthermore, phosphorylation of tau by cdk5 was not significantly increased in methylmercury-treated cerebellar neurons. These results indicate that the molecular mechanism underlying the methylmercury-induced neuronal death involves not solely the calpain/p35/cdk5 cascade but also some other pathways.
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