A study of hypoxic oligodendroglial injury

少突胶质细胞缺氧损伤的研究

基本信息

批准号：
10670611
负责人：
YOSHIOKA Akira
金额：
$ 0.96万
依托单位：
Kanazawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670611/
关键词：
oligodendroglia hypoxia cell death exctitotoxicity cyclic AMP cyclic GMP Na+Ca2+exchanger Na+Ca2+exchanger cGMP

项目摘要

Previously, we have found that CaィイD12+ィエD1 accumulation via non-N-methyl-D-aspartate (NMDA) glutamate receptor (GluR) mediates oxygen-glucose deprivation induced oligodendroglial injury. In the present study, we investigated the mechanism of CaィイD12+ィエD1 accumulation when non-NMDA GluR are activated in oligodendroglial cells. Oligodendroglial cells express mRNAs encoding each of the three known NaィイD1+ィエD1-CaィイD12+ィエD1 exchanger isoforms. Kainate-induced oligodendroglial CaィイD12+ィエD1 accumulation is dimished by replacement of extracellular NaィイD1+ィエD1 with N-methyl-D-glucamine, and by the NaィイD1+ィエD1-CaィイD12+ィエD1 exchanger blockers, 3, 4-dichlorobenzamil (DCB) and benzamil. These results indicate that kainate-induced CaィイD12+ィエD1 accumulation results, at least in part, from NaィイD1+ィエD1-CaィイD12+ィエD1-mediated exchange of intracellular NaィイD1+ィエD1 for extracellular CaィイD12+ィエD1. We previously found that agents which elevate intracellular cAMP or cGMP inhibit kainate-induced CaィイD12+ィエD1 accumulation and prevent kainate induced excitotoxicity. To test the hypothesis that cAMP and cGMP inhibit "reverse" mode operation of NaィイD1+ィエD1-CaィイD12+ィエD1 exchangers, we loaded oligodendroglia with NAィイD1+ィエD1 in the absence of quaint by incubation with veratridine and ouabain in an NaィイD1+ィエD1 containing medium. This caused CaィイD12+ィエD1 accumulation, which was inhibited by agents that elevate intracellular cMAP or cGMP prevent oxygen-glucose deprivation-induced oligodendroglial injury by inhibiting "reverse" mode operation of NaィイD1+ィエD1-CaィイD12+ィエD1 exchangers.

此前，我们发现CaiD12+CaiD1通过非N-甲基-D-天冬氨酸（NMDA）谷氨酸受体（GluR）积累介导缺氧葡萄糖诱导的少突胶质细胞损伤。在本研究中，我们研究了CaiD12+D1的机制。当少突胶质细胞中的非 NMDA GluR 被激活时，少突胶质细胞表达编码每种的 mRNA。三种已知的 NaiD1+D1-CaD12+D1 交换异构体通过用 N-甲基-D-葡萄糖胺替代细胞外 NaD1+D1 以及 NaiD1+D1-CaD12+D1 交换阻断剂来减少。 , 3, 4-二氯苯扎米尔 (DCB) 和苯扎米尔。这些结果表明，红藻氨酸诱导的 CaD12+D1 积累至少部分是由 NaD1+D1-CaD12+D1 介导的细胞内 CaD1+D1 与细胞外 CaD12+D1 的交换所致。先前发现，提高细胞内 cAMP 或 cGMP 的药物会抑制为了测试 cAMP 和 cGMP 抑制 NaD1+D1-CaD12+D1 交换器“反向”模式操作的假设，我们在缺乏 NAiD1+IeD1 的情况下加载少突胶质细胞。与藜芦定和哇巴因一起孵育含有 NaD1+D1 的培养基会导致 CaD12+D1 积聚，而 CaD12+D1 积聚可被提高细胞内 cMAP 或 cGMP 的药物抑制，通过抑制 NaD1+D1-CaD12+D1 交换器的“反向”模式操作来防止缺氧诱导的少突胶质细胞损伤。。