A study of hypoxic oligodendroglial injury

少突胶质细胞缺氧损伤的研究

• 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

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.

以前，我们已经发现，通过非N-甲基-D-天冬氨酸（NMDA）谷氨酸受体（GluR）的Ca ~（2+）D_（12+）D_（11）积累介导氧-糖剥夺诱导的少突胶质细胞损伤。在本研究中，我们研究了在少突胶质细胞中，当非NMDA GluR被激活时，Ca ~（2+）D_（12）+Ca ~（2+）D_（1）积聚的机制。少突胶质细胞表达编码三种已知Na + D1+ Ca + D1-Ca + D12+ Ca + D1交换体同种型的mRNA。用N-甲基-D-葡糖胺替代细胞外Na + D1+ Na + D1，以及Na + D1 + Na + D1-Ca + D12 + Na + D1交换阻断剂，3，4-二氯苯甲脒（DCB）和苯甲脒，可减少红藻氨酸诱导的少突胶质细胞Ca + D12 + Na + D1积累。这些结果表明，红藻氨酸诱导的Ca ~（2+）D_12 + Ca ~（2+）D_1积累至少部分是由于Na ~（2+）D_1 + Ca ~（2+）D_1-Ca ~（2+）D_12 + Ca ~（2+）D_1介导的细胞内Na ~（2+）D_1 + Ca ~（2+）D_1与细胞外Ca ~（2+）D_12 + Ca ~（2+）D_1的交换。我们以前发现，提高细胞内cAMP或cGMP的药物抑制红藻氨酸诱导的Ca ~（2+）D_12 + Ca ~（2+）D_1积累，并防止红藻氨酸诱导的兴奋性毒性。为了检验cAMP和cGMP抑制Na + D1+ Ca 2 + D1-Ca 2 + D12+ Ca 2 + D1交换器的“反向”模式操作的假设，我们通过在含有Na + D1+ Ca 2 + D1的培养基中与藜芦碱和哇巴因一起孵育，在不存在古雅的情况下用Na + D1 + Ca 2 + D1加载少突胶质细胞。这导致Ca ~（2+）D_12 + Ca ~（2+）D_1积累，其被升高细胞内cMAP或cGMP的试剂抑制，通过抑制Na ~（2+）D_1 + Ca ~（2+）D_1-Ca ~（2+）D_12 + Ca ~（2+）D_1交换器的“反向”模式操作来防止氧-葡萄糖剥夺诱导的少突胶质细胞损伤。

项目成果

Akira Yoshioka et al.: "Ibudilast prevents oxygen-glucose deprivation-induced oligodendroglial injury"Brain and Nerve. 51. 49-54 (1999)

Akira Yoshioka 等人：“异布司特可预防缺氧葡萄糖引起的少突胶质细胞损伤”大脑和神经。

吉岡亮ら: "虚血性神経細胞死"山嶋哲盛、サイメッド・パブリケーションズ. 189 (1998)

Ryo Yoshioka 等：“缺血性神经元死亡”Tetsumori Yamashima，Cymed Publications 189 (1998)。

A.YOSHIOKA et al.: "Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity" Journal of Neurochemistry. 70. 2416-2423 (1998)

A.YOSHIOKA 等人：“环 AMP 升高剂可预防少突胶质细胞兴奋性毒性”《神经化学杂志》。

A. Yoshioka et al: "Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line"Journal of Neurochemistry. 74. 633-640 (2000)

A. Yoshioka 等人：“环 GMP/环 GMP 依赖性蛋白激酶系统可防止永生化少突胶质细胞系的兴奋性毒性”《神经化学杂志》。

Akira Yoshioka et al.: "Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line"Journal of Neurochemistry. 74. 633-640 (2000)

Akira Yoshioka 等人：“环 GMP/环 GMP 依赖性蛋白激酶系统可防止永生化少突胶质细胞系的兴奋性毒性”神经化学杂志。