Glutamate dehydrogenase in spinocerebellar degeneration.

脊髓小脑变性中的谷氨酸脱氢酶。

• 批准号: 61570386
• 负责人: TAKAHASHI Mitsuo
• 金额: $ 1.15万
• 依托单位: Osaka University Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570386/
• 关键词: 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

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.

脊髓小脑变性是一种异质性疾病，其发病机制和病因尚不清楚。我们已经证实，谷氨酸脱氢酶（GDH）活性降低在白细胞和/或成纤维细胞从四个病人。其中3例表现为进行性小脑功能障碍和其他体征，包括皮质脊髓、动眼肌功能障碍和周围神经病变。一个表现出非典型帕金森症。我们的实验是为了这两个目的而做的。首先，研究了GDH在白细胞中减少的机制。我们建立了测定白细胞中GDH蛋白含量的放射免疫法。4个病人的蛋白质含量下降，其比例与酶活性成正比。GDH特异性活性在正常对照、患病对照和GDH缺乏症患者中一致。这些结果表明，GDH的减少不是由于结构变化导致质变，而是由于GDH蛋白的减少。为了探讨GDH生物合成途径受影响的可能性，对GDH蛋白加工过程的研究正在进行中。其次，试图了解GDH缺陷是否导致细胞死亡。与正常对照相比，培养的成纤维细胞对高浓度的l -谷氨酸具有敏感性。这些细胞在24小时内表现为退化和丧失活力。这些结果提示本病例存在GDH活性的全身性异常，GDH介导的代谢过程受损对细胞（可能是神经元细胞）具有致病性。

项目成果

C.Tatsumi: Acta Neurol.Scand.

C.Tatsumi：Acta Neurol.Scand。

K. Kajiyama: "Decreased glutamate dehydrogenase protein in spinocerebellar degeneration." J. Neurol. Neurosurg. Psychiatry.

K. Kajiyama：“脊髓小脑变性中谷氨酸脱氢酶蛋白减少。”

梶山幸司: 臨床神経学(抄). 27. 1696 (1987)

梶山浩二：临床神经病学（摘要）27. 1696 (1987)。

K.Kajiyama: J.Neurol.Neurosurg.Psychiatry.

K.Kajiyama：J.Neurol.Neurosurg.Psychiatry。

C. Tatsumi: "Decreased glutamate dehydrogenase activity in spinocerebellar degeneration." Clin. Neurol.27. 1696 (1987)

C. Tatsumi：“脊髓小脑变性中谷氨酸脱氢酶活性降低。”