Different mechanisms of glutamate‐induced neuronal death between dopaminergic and non‐dopaminergic neurons in rat mesencephalic culture
Different mechanisms of glutamate‐induced neuronal death between dopaminergic and non‐dopaminergic neurons in rat mesencephalic culture
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大鼠中脑培养物中多巴胺能和非多巴胺能神经元谷氨酸诱导神经元死亡的不同机制
DOI：
10.1002/(sici)1097-4547(19960215)43:4
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发表时间：
1996
影响因子：
4.2
通讯作者：
Jun Kimura
中科院分区：
文献类型：
--
作者：
H. Sawada;T. Kawamura;S. Shimohama;Akinori Akaike;Jun Kimura
帕金森病以多巴胺能神经元变性为特征，但其发病机制尚不清楚。在多巴胺能神经元中，通过多巴胺氧化释放氧自由基，例如过氧化氢。许多因素参与自由基形成，但谷氨酸和一氧化氮（NO）是主要通过钙内流介导的自由基诱导的神经毒性的主要效应物。在培养的胚胎大鼠中脑中，我们研究了谷氨酸和NO产生剂诱导的多巴胺能和非多巴胺能神经元死亡。虽然谷氨酸对多巴胺能和非多巴胺能神经元都有神经毒性作用，但它对多巴胺能神经元的作用略大。与谷氨酸相反，NO生成剂（S-亚硝基半胱氨酸和硝普钠）显示出仅限于非多巴胺能神经元的神经毒性作用。NO合成酶抑制剂NO-硝基-L-精氨酸对谷氨酸诱导的多巴胺能神经元细胞毒性无明显影响，但对非多巴胺能神经元细胞毒性有明显拮抗作用。这些发现表明存在两种不同的谷氨酸诱导的神经元死亡机制，一种是在多巴胺能神经元中发现的非NO介导的神经毒性，另一种是在非多巴胺能神经元中发现的通过NO介导的神经毒性。© 1996 Wiley利斯公司
Parkinson's disease is characterized by dopaminergic neuronal degeneration, but its pathogenic mechanism is still unknown. In the dopaminergic neurons, oxygen radicals such as hydrogen peroxide are released through dopamine oxidation. Many factors are involved in radical formation, but glutamate and nitric oxide (NO) are the major effectors of the radical‐induced neurotoxicity mediated primarily through calcium influx. In the cultured embryonic rat mesencephalon, we investigated the dopaminergic and non‐dopaminergic neuronal death induced by glutamate and by NO‐generating agents. Although glutamate had a neurotoxic effect on both dopaminergic and non‐dopaminergic neurons, it showed slightly greater effect in the dopaminergic neurons. In contrast to glutamate, NO‐generating agents (S‐nitrosocysteine and sodium nitroprusside) showed neurotoxic effects restricted exclusively to non‐dopaminergic neurons. Although No‐nitro‐L‐arginine, an NO synthase inhibitor, had no significant effect on the glutamate‐induced cytotoxicity in dopaminergic neurons, it had a significant antagonistic effect on that in non‐dopaminergic neurons. These findings indicate the presence of two different mechanisms of glutamate‐induced neuronal death, one being neurotoxicity not mediated by NO, found in dopaminergic neurons, and the other being that mediated via NO, found in non‐dopaminergic neurons. © 1996 Wiley‐Liss, Inc.
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DOI：
10.1073/pnas.88.14.6368
发表时间：
1991-07-01
影响因子：
11.1
作者：
DAWSON, VL;DAWSON, TM;SNYDER, SH
通讯作者：
SNYDER, SH
DOI：
10.1073/pnas.87.4.1620
发表时间：
1990-02-01
影响因子：
11.1
作者：
BECKMAN, JS;BECKMAN, TW;FREEMAN, BA
通讯作者：
FREEMAN, BA
影响因子：
56.9
作者：
STAMLER, JS;SINGEL, DJ;LOSCALZO, J
通讯作者：
LOSCALZO, J
DOI：
10.1073/pnas.86.22.9030
发表时间：
1989-11-01
影响因子：
11.1
作者：
BREDT, DS;SNYDER, SH
通讯作者：
SNYDER, SH