Glutamate dehydrogenase in spinocerebellar degeneration.
| Project/Area Number |
61570386
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Osaka University Medical School |
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Principal Investigator |
TAKAHASHI Mitsuo Osaka University Medical School, 医学部, 講師 (20028492)
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| Co-Investigator(Kenkyū-buntansha) |
巽 千賀夫 大阪大学, 医学部附属病院, 医員
梶山 幸司 大阪大学, 医学部附属病院, 医員
UENO Satoshi Osaka University Medical School, 医学部, 助手 (40184949)
KAJIYAMA Koji Osaka University Hospital
TATSUMI Chikao Osaka University Hospital
依藤 史郎 大阪大学, 医学部, 助手 (80191675)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1987: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Glutamate dehydrogenase / spinocerebellar degeneration / enzyme activity / Protein content / leukocyte / fibroblast / グルタミン酸 / グルタミン脱水素酵素欠損症 / GDH酵素活性値 / GDH酵素蛋白量 / 皮膚線維芽細胞 |
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| Research Abstract |
Spinocerebellar degeneration is a heterogeneous diseas complex and its pathogenesis and etiology are completely unknown. We have confirmed that glutamate dehydrogenase (GDH) activity is reduced in leukocytes and /or fibroblasts from four patients. Three of them manifested progressive cerebellar dysfunction and additional signs including corticospinal, oculomotor dysfunctions and peripheral neuropathy. The one showed atypical parkinsonism. Our experiments were made for the two purposes. Firstly, the mechanism by which GDH was reduced in leukocytes was studied. We established the radioimmunoassay for the determination of GDH protein contents in leukocytes. The protein content was decreased in the four patients and its ration was proportional to the enzyme activity. The GDH specific activity was consistent in normal controls, diseased controls, and patients with GDH deficiency. These results showed that the reduction of GDH was not due to the structural changes leading to qualitative changes but due to decreased GDH protein. The study of the processing of GDH protein is underprogress in order to examine the possibility that biosynthetic pathway of GDH is affected. The secondly, an attempt was made to see whether GDH deficit was pathogenic for cell death. The cultured fibroblasts had a sensitivity to a high concentrations of L-glutamate compared to normal controls. These cells showed degeneration and lossof viability within 24 hrs. All these results suggested that the cases presented here had the systemic abnormality of GDH activity, and impaired metabolism in GDH mediated process was pathogenic for the cell, possibly neuronal cells.
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Report
(2 results)
Research Products
(10 results)
