Analysis of An Intracellular Ca^<2+>-release Factor, Cyclic ADP-ribose, in Brain

脑中细胞内Ca^2-释放因子环ADP-核糖的分析

基本信息

批准号：
08671123
负责人：
TAKAHASHI Katsunobu
金额：
$ 1.41万
依托单位：
Department of Mental Disorder Research, National Institute of Neuroscience, NCNP
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671123/
关键词：
Cyclic ADP-ribose Brain DC38 Neuropsychiatric disease 環状ADPリボース

项目摘要

Cyclic adenosine diphosphoribose (cyclic ADP-ribose), a metabolite of beta-NAD<@D1+@>D1, was first discovered in sea urchin eggs by Lee and his colleagues as a novel intracellular messenger with Ca<@D12+@>D1-imbilizing activity. It is expected that the cyclic nucleotide mediates Ca<@D12+@>D1release from an inositol 1,4,5-triphosphate-insensitive Ca<@D12+@>D1 store. The cyclic ADP-ribose-synthesizing enzyme, termed ADP-ribosyl cyclase, is especially abundant in Aplysia ovotestis, from which it was purified as a 29 kDa cytoplasmic protein and sequenced. Interestingly, the ADP-ribosyl cyclase has an amino acid sequence homologous to that of human CD38 antigen which is a 46-kDa type II glycoprotein with a single-transmembrane domain. To investigate cyclic ADP-ribose in mammalian brain, we developed radioimmunoassay for the cyclic nucleotide, and obtained the follwing findings.1. Content of cyclic ADFP-ribose in brain (163(]SY.+-。[)9 pmol/g tissue) was the highest amoung rat tissues tested. No correlation of the content and CD38 expression in tissues was observed. 2. The investigation of anatomical distribution of cyclic ADP-ribose in rat brain revealed that the cyclic nucleotide was abundant in all regions of brain tissue (150-250 pmol/g tissue). 3. Cyclic ADP-ribose in rat cerebral cortex was localized mainly in synapostsomal fraction (47% of total) and cytosolic fracion (39%). 4. High contents of cyclic ADP-ribose were detected in frontal cortex (498(]SY.+-。[)59 pmol/g tissue) and parietal cortex (591(]SY.+-。[)92 pmol/g tissue) of human post-mortam brains, which wer 3-4 times higher than that of rat cerebral cortex. 5. There were no sttistically significant difference between the cyclic ADP-ribose contetns in the parietal cortex of controls and those of patients with schizoprenia, dementia of the Alzheimer type or vasclular dementia.

Lee和他的同事在Sea Hilchin Eggs中首次发现了β-NAD <@D1+@> d1的环状腺苷二磷酸蛋白（环状ADP-核糖），这是由Lee和他的同事作为一种新型的细胞内Messenger在Sea Hilchin Eggs中发现的，具有CA <@d12+@d12+@> d12+@> d12+@> d1-> d1-> d1- imbillized活动。可以预期，从1,4,4,5-磷酸盐不敏感的CA <@d12+@> d1 store中介导了ca <@d12+@> d1release ca <@d12+@> d1release。环状ADP-ribose合成酶称为ADP-核糖基环酶，在Ovotestis中特别丰富，从中纯化为29 kDa的细胞质蛋白并进行了测序。有趣的是，ADP-核糖基环化酶具有与人CD38抗原同源的氨基酸序列，该氨基序列是具有单跨膜结构域的46 kDa II型糖蛋白。为了研究哺乳动物大脑中的环状ADP-核糖，我们为环状核苷酸开发了放射免疫测定法，并获得了Follwing发现。1。大脑中环状ADFP-核糖的含量（163（]SY。+ - 。[）9 pmol/g组织是测试最高的大鼠组织。没有观察到组织中含量和CD38表达的相关性。 2。循环ADP-核糖在大鼠脑中的解剖学分布的投资表明，脑组织的所有区域（150-250 pmol/g组织）的环状核苷酸均丰富。 3。大鼠脑皮质中的环状ADP-核糖主要定位于突触体馏分（占总数的47％）和胞质平面（39％）。 4。在额叶皮层（498（]SY。+ - 。[）59 pmol/g组织）和顶叶皮层（591（]SY。+ - 。[）92 pmol/g组织中检测到循环ADP-核糖的高含量。 5。在对照组皮层中的环状ADP-ribose contns与精神分裂症患者，阿尔茨海默氏症类型痴呆或血管痴呆的痴呆症之间没有明显的差异。