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.

环状腺苷二磷酸核糖（环状 ADP-核糖）是 β-NAD<@D1+@>D1 的代谢产物，最初由 Lee 和他的同事在海胆卵中发现，作为一种新型细胞内信使，具有 Ca<@D12+@>D1 固定作用预期环核苷酸介导Ca D12+D1 从肌醇的释放。 1,4,5-三磷酸不敏感的Ca D12+D1 储存环ADP-核糖合成酶，称为ADP-核糖基环化酶，在海兔卵睾中特别丰富，它被纯化为29 kDa 的细胞质。蛋白质和测序表明，ADP-核糖基环化酶具有与人 CD38 抗原同源的氨基酸序列它是一种具有单跨膜结构域的46 kDa II型糖蛋白。为了研究哺乳动物脑中环ADP-核糖的含量，我们开发了环核苷酸的放射免疫分析方法，并获得了以下结果： 1． (163(]SY.+-.[)9 pmol/g组织)在测试的大鼠组织中含量最高，与组织中CD38表达没有相关性。 2. 大鼠脑中环ADP-核糖的解剖分布研究表明，环核苷酸在脑组织的所有区域中含量丰富（150-250 pmol/g 组织）。 3. 大鼠大脑皮层中环ADP-核糖。主要集中在突触体部分（占总数的 47%）和胞质部分（39%）。 4. 检测到高含量的环状 ADP-核糖。额叶皮质 (498(]SY.+-. [)59 pmol/g 组织) 和人死后大脑顶叶皮质 (591(]SY.+-.[)92 pmol/g 组织)，比大鼠大脑皮质高 3-4 倍 5。对照组顶叶皮质中的环状 ADP-核糖含量与精神分裂症、阿尔茨海默型痴呆或血管性痴呆患者的顶叶皮质中的环状 ADP-核糖含量没有统计学上的显着差异。失智。