| Project/Area Number |
16590073
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Setsunan University |
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Principal Investigator |
OGITA Kiyokazu Setsunan University, Pharmacology, Professor, 薬学部, 助手 (90169219)
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Chie Setsunan University, Pharmacology, Assistant, 薬学部, 助手 (90388645)
YONEDA Yukio Kanazawa University, Molecular Pharmacology, Professor, 大学院・自然科学研究科, 教授 (50094454)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Glutamate / Neuronal death / Mitochondria / RNase / Cerebral cortex / Primary cultured neuron / RNA / NMDA / 遺伝子発現制御 / カイニン酸 / 転写因子 / DNA / トリメチルスズ / 海馬 / 神経細胞死 |
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| Research Abstract |
A decline in the mitochondrial RNA transcripts and protein synthesis, as well as mitochondrial DNA damage, is considered to induce mitochondrial injury to cause neuronal death. To evaluate involvement of mitochondrial dysfunction in glutamate-induced neuronal death, in this study, we examined the effects of glutamate exposure on mitochondrial RNA level in primary cultured cortical neurons of mice. Cerebral cortex was dissected in 15 days-old fetal mouse to obtain neural cells. Cultured cortical neurons (12 DIV) obtained were exposed to glutamate for 15 min at 100 μM. Glutamate treatment led to a significant decrease in mRNA of ND1 and ND6, which are subunits of NADH-ubiquinone oxidoreductase, before cell death. As mitochondrial RNAs level is regulated at least in part by RNA degradation by RNase-L, we next examined the effect of glutamate exposure on expression of RNase-L. RT-PCR analysis revealed that glutamate was effective in increasing the level of RNase-L mRNA at least 2-12 h after treatment. The increase in expression of RNase-L was abolished by the NMDA receptor antagonist MK801. There results suggest that activation of NMDA receptor by glutamate reduces mitochondrial RNA level through enhanced expression of RNase-L in primary cultured cortical neurons.
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