The presence of mutant HTLV-I in the central nervous system
中枢神经系统中存在突变型 HTLV-I
基本信息
- 批准号:06670656
- 负责人:
- 金额:$ 1.41万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (C)
- 财政年份:1994
- 资助国家:日本
- 起止时间:1994 至 1995
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
For these ten years we have studied the pathogenetic mechanism of globoid cell leukodystrophy, a genetic demyelinating disorder deficient in galctosylceramidase I activity, and reported that galactosylsphingosine, a lyso compound of galactosylceramide, accumulates in the tissue of the patients and suggested that the cytotoxicity of the acumulated lysocompound leads to the cell death and subsequent demyelination. We have also the accumulation of lysocompounds in other lipid storage diseases such as GM1 gangliosidosis and metachromatic leukodystrophy. For one of the treatment of these lipid storage diseases we hypothesized if we could detoxicate the accumulated lysosphingolipids, and we obtained some data on this project as follows :1. In 1994, we examined the synthetic pathway of the lysosphingolipid, When conduritol B epoxide (CBE), a competitive inhibitor of beta-glucosidase, was included in the medium of cultured fibroblasts, the accumulation of glucosylsphingosine, a lysocompound of … More glocosylceramide, was observed. The accumulated glucosylsphingosine was dependent on the dose of added CBE.Next, we added in the medium both CBE and PDMP, an inhibitor of glucosylceramide synthesis, and found the deceased accumulation of glucosylsphingosine. From these data we concluded that the synthesis of glucosylsphingosine is catalyzed not only by the glucosylation of sphingosine but also by the deacylation of glucosylceramide.2. In 1995, we examined the degradative pathway of the lysospingolipid. For this purpose, we characterized molecular properties of galactosylceramidase I, a degrading enzyme of galactosylsphingosine and found mutations in adult patients with globod cell leukodystrophy. We obtained cDNA fragments of the gene after amplification by PCR from the patients and sequenced the total nucleotides in the amino acid coding region. In the 4 patients, we found new point mutations which replace evolutionally-conserved amino acids to others. We are now atempting to confirm that the mutations found in the patients are causative for the deficiency of the enzyme activity by expression of the mutated cDNA in eucaryotic cells. Less
近十年来,我们研究了球样细胞脑白质营养不良的发病机制,这是一种缺乏半乳糖神经酰胺酶I活性的遗传性脱髓鞘疾病,并报道了半乳糖神经酰胺的溶血化合物半乳糖鞘氨醇在患者组织中的积累,并提出积累的溶血化合物的细胞毒性导致细胞死亡和随后的脱髓鞘。我们也有其他脂质储存疾病,如GM 1神经节苷脂沉积症和异染性脑白质营养不良中的溶解化合物的积累。对于这些脂质储存疾病的治疗之一,我们假设如果我们可以解毒积累的溶血鞘脂,我们获得了一些数据,在这个项目如下:1。在1994年,我们研究了溶血鞘脂的合成途径,当β-葡萄糖苷酶的竞争性抑制剂conduritol B epoxide(CBE)被包括在培养的成纤维细胞培养基中时, ...更多信息 葡萄糖神经酰胺。葡萄糖鞘氨醇的积累量与CBE的添加量有关,其次,我们在培养基中添加CBE和葡萄糖神经酰胺合成抑制剂PdR,发现葡萄糖鞘氨醇的积累量下降。从这些数据中我们得出结论,葡萄糖鞘氨醇的合成不仅是由鞘氨醇的葡萄糖基化催化的,而且也是由葡萄糖神经酰胺的脱酰催化的. 1995年,我们研究了溶血鞘脂的降解途径。为了这个目的,我们的特点半乳糖神经酰胺酶I,半乳糖鞘氨醇的降解酶的分子特性,并发现在成人患者的球状细胞脑白质营养不良的突变。我们从患者中扩增该基因的cDNA片段,并对氨基酸编码区的总核苷酸进行测序。在4例患者中,我们发现了新的点突变,这些点突变将进化上保守的氨基酸替换为其他氨基酸。我们现在试图通过在真核细胞中表达突变的cDNA来证实在患者中发现的突变是酶活性缺乏的原因。少
项目成果
期刊论文数量(28)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ymada T, and Kobayashi, T.: "The mutation in amyloid precursor protein inhibits both α-and β-secretion" Neurosci. Lett.191. 103-106 (1995)
Ymada T 和 Kobayashi, T.:“淀粉样前体蛋白的突变同时抑制 α 和 β 分泌” Neurosci.103-106 (1995)。
- DOI:
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- 影响因子:0
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- 通讯作者:
Kobatashi T.et al.: "Adrenoleukodystrophy gene encodes an 80 kDa membrane protein." Biochem. Biophys. Res. Commun.201. 1027-1034 (1994)
Kobatashi T.et al.:“肾上腺脑白质营养不良基因编码 80 kDa 膜蛋白。”
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
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- 通讯作者:
Kobayashi T,Yamada T: "Adrenoleukodystrophy gene encodes and 80KDa membrane protein" Biochem.biophys.Res.Commun.201. 1027-1034 (1994)
小林 T,山田 T:“肾上腺脑白质营养不良基因编码和 80KDa 膜蛋白”Biochem.biophys.Res.Commun.201。
- DOI:
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- 影响因子:0
- 作者:
- 通讯作者:
小林卓郎: "遺伝性白質変性症の病態" 福岡医学雑誌. 86. 330-333 (1995)
Takuro Kobayashi:“遗传性白质变性的病理学”福冈医学杂志 86. 330-333 (1995)。
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- 影响因子:0
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Yamaguti Y,Sasagasako N: "The synthetic pathway for glucosylsphingosine in cultured fibroblasts" Journal of Biochemistry. 116. 704-710 (1994)
Yamaguti Y,Sasagasako N:“培养成纤维细胞中葡萄糖基鞘氨醇的合成途径”生物化学杂志。
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KOBAYASHI Takuro其他文献
KOBAYASHI Takuro的其他文献
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{{ truncateString('KOBAYASHI Takuro', 18)}}的其他基金
CO2 and H2S fixation and clean bio-methane production using a photoreactor process
使用光反应器工艺固定 CO2 和 H2S 并清洁生物甲烷生产
- 批准号:
25740056 - 财政年份:2013
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Purification and cDNA cloning of galactosylceramidase 1
半乳糖神经酰胺酶1的纯化和cDNA克隆
- 批准号:
02454246 - 财政年份:1990
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
Study on the mechanism of demyelination in hereditary leukodystrophy
遗传性脑白质营养不良脱髓鞘机制研究
- 批准号:
63570367 - 财政年份:1988
- 资助金额:
$ 1.41万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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