| Project/Area Number |
20590971
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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 |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMADA Hideomi The University of Tokyo, 医学部附属病院, 助教 (60396752)
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| Co-Investigator(Kenkyū-buntansha) |
GEORGE Seki 東京大学, 医学部附属病院, 講師 (30206619)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | NBC1(NBCe1) / RTA / NBCe1 / 片頭痛 / NBC1 |
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| Research Abstract |
NBC1(NBCe1) belongs to bicarbonate transporter family(SLC4). This transporter plays an important role of adjusting the intracellular and/or extracellular pH to maintain the concentration of bicarbonate. The dysfunction of NBC1 brings on several and severe symptoms enough to threaten the life. This disease causes not only severe proximal renal tubular acidosis, but also symptoms of severe ocular-abnormalities (band-keratopathy, cataract, and glaucoma). Some patients suffering from these abnormalities develop blindness. They also have a high rate of migraine occurrence. Because NBC1 presents in the glia cells of the brain, NBC1 must work and maintain pH of the synaptic cleft. As NBC1 controls activities of neurotransmitters by pH in the cleft, the NBC1 mutants, which dose not express in the membrane, can not control right stable pH of the synaptic cleft. Because low pH of the cleft induces the abnormal signal of neurotransmitters, patients must have such a migraine. In addition, we reported that among several NBC1 SNPs, K558R had less activity of NBC1. NBC1 works on the membrane as a dimeric form. We also showed some of NBC1 mutants exert dominant negative effects on the wild-type NBC1. This fact raises a possibility that SNPs of NBC1 may cause migraine. The investigation of NBC1 may help further clarify the pathogenesis of migraine.
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