Spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase during mouse postnatal development  

D-型丝氨酸、丝氨酸消旋酶及D-型氨基酸氧化酶在小鼠出生后个体发育中的分布变化及相互关系

作　　者：王立真[1] 朱兴族[1] 

机构地区：[1]中国科学院上海生命科学研究院药物研究所药理室

出　　处：《Acta Pharmacologica Sinica》2003年第10期965-974,1060,共11页中国药理学报（英文版）

基　　金：Project supported by Grant G (1998) 051108 from the Ministry of Science and Technology of China.

摘　　要：AIM: To elucidate the spatiotemporal relationships among D-serine, serine racemase, and D-amino acid oxidase (EC 1.4.3.3; DAO) in mouse cortex, striatum, cerebellum, heart, lung, liver, spleen, kidney, and skeletal muscle during mouse postnatal development. METHODS: The transcription levels of serine racemase and DAO were assayed by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of serine racemase were examined by Western blot. DAO activities were assayed by colorimetric method. D-serine was measured by HPLC. RESULTS: In cortex, striatum, and cerebellum, free D-serine increased drastically after birth and coincided well with the increase of serine racemase expression. However, among the 9 tissues examined, DAO activities were detected only in cerebellum and kidney. During the 3rd week, DAO activity in cerebellum and kidney increased dramatically, which concurred with the drastic decline of D-serine content in these tissues. On the other hand, while D-serine and serine racemase fall to trace level in cerebellum and kidney at the 3rd weekend, DAO activities in these tissues increased continuously. CONCLUSION: The free D-serine is mainly synthesized by serine racemase. However, novel mechanisms might be involved in D-serine deposition in mouse tissues with high level of D-serine and no detectable DAO activity such as cortex and striatum. DAO in cerebellum and kidney might have other physiological functions in addition to degrading D-amino acid.目的:探讨小鼠个体发育过程中皮层、纹状体、小脑、心脏、肺、肝脏、脾脏、肾脏和骨骼肌中口型丝氨酸,丝氦酸消旋酶(SR)及口一型氨基酸氧化酶(DA0)的分布特征及相互关系.方法:RT PCR法检测SR和DA0 mRNA水平;Weste r『lblot检测SR蛋白水平;比色法检测DAO酶活力;高效液相法检测游离口型幺幺氨酸含量.结果:小鼠出生后早期个体发育过程中皮层、纹状体和小脑内游离口型丝氨酸含量急剧增加并伴有SR平行增加.在检测组织中,仪小脑和肾脏可检测到DAO酶活力,且随着小脑和肾脏内DAO酶活力的增加,口一型丝氨酸含量急剧下降,并在出生后第三周末降至成年微量水平,但此时DA0酶活力却仍不断增加. 结论:哺乳动物体内口型丝氨酸主要由SR催化生成,但在皮层和纹状体等口犁丝氨酸浓度很高,但缺乏DA0的组织中沪型丝氦酸的降解尚有其它机制参与.小脑和肾脏l{l的I)A(}除参‘j口型氨基酸代谢外,可能还具有j土它的乍理功能.

关 键 词：D-amino acid oxidase SERINE serine racemase inbred C57BL mice 

分 类 号：R341[医药卫生—基础医学]