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The Physiological Role of D-Amino Acid Oxidase in the Mammalian Central Nervous System

D-氨基酸氧化酶在哺乳动物中枢神经系统中的生理作用

基本信息

批准号：
60580150
负责人：
HORIIKE Kihachiro
金额：
$ 1.02万
依托单位：
Shiga University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

To elucidate the physiological role of D-amino acid oxidase (DAO), a flavin-containing peroxisomal enzyme, in the mammalian central nervous system, it isimportant to explore the histological localization of DAO and its correlation to the oxidizing activity of thiazolidine-2-carboxylate (TC), which is an adduct of cysteamine and glyoxylate and is believed to be a physiological substrate for DAO.Using serial fixed sections, we carried out a histochemical study on DAO in the whole brain of rat by a sensitive peroxidase-coupled procedure which we devised for histochemical detection of DAO activity. This method is based on the intensifying effect of nickel ions on diaminobenzidinebased product formation with peroxidase. DAO activity was found to be localized exclusively in the lower brain stem, cerebellum and spinal cord, and to be present only in astrocytes and Bergmann glial cells, but not in neuronal components, endothelial cells or ependymal cells. Form electron microscopic observations, the greater proportion of DAO activity was present in the glial spaces around various kinds of synapses. We also applied the above technique for the detection of TC oxidase activity. The localizations of this oxidase activity in the kidney, liver and brain of rat were in accord with those of DAO. On the other hand, the activity of D-aspartate oxidase, another peroxisomal flavoenzyme, was found in the endbrain in which DAO activity was not detectable.The above results clearly demonstrate the regional differentiation of astrocytes and the uneven distribution of peroxisomal enzymes in the brain. It is also suggested the possibility that DAO is involved in the metabolic regulation by controlling the intracellular level of cysteamine and its metabolite, an oxalyl thiol ester, which are known to be metabolic effectors.

为了阐明D-氨基酸氧化酶（DAO）在哺乳动物中枢神经系统中的生理作用，必须研究DAO的组织学定位及其与噻唑烷-2-羧酸（TC）氧化活性的关系。TC是半胱胺和乙醛酸的加合物，被认为是DAO的生理底物。本实验采用过氧化物酶偶联法对大鼠脑内DAO进行了组织化学研究。该方法基于镍离子对过氧化物酶形成二氨基联苯胺基产物的增强作用。DAO活性被发现只局限于下脑干，小脑和脊髓，并只存在于星形胶质细胞和Bergmann胶质细胞，但不存在于神经元成分，内皮细胞或室管膜细胞。电镜观察发现，大部分DAO活性存在于各种突触周围的胶质间隙中。我们还将上述技术应用于TC氧化酶活性的检测。该氧化酶在大鼠肾、肝、脑中的定位与DAO的定位雅阁。另一方面，在DAO活性检测不到的终脑中，发现了另一种过氧化物酶体黄素酶--D-天冬氨酸氧化酶的活性。上述结果清楚地表明了星形胶质细胞的区域分化和过氧化物酶体酶在脑中的不均匀分布。还表明DAO通过控制细胞内半胱胺及其代谢物草酰硫醇酯（已知为代谢效应物）的水平参与代谢调节的可能性。