Prostaglandin E2 deteriorates N-methyl-D-aspartate receptor-mediated cytotoxicity possibly by activating EP2 receptors in cultured cortical neurons
Prostaglandin E2 deteriorates N-methyl-D-aspartate receptor-mediated cytotoxicity possibly by activating EP2 receptors in cultured cortical neurons
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DOI：
10.1016/j.lfs.2005.08.026
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发表时间：
2006-03-13
期刊：
影响因子：
6.1
通讯作者：
Ohyashiki, T
中科院分区：
文献类型：
--
作者：
Takadera, T;Ohyashiki, T
谷氨酸受体，特别是 N-甲基-D-天冬氨酸 (NMDA) 受体的激活，在脑缺血的早期阶段启动缺血级联反应。缺血后，脑缺血也与导致组织损伤的炎症反应有关。据报道，脑缺血损伤后会发生神经元环氧合酶-2 (COX-2) 的上调和前列腺素 E-2 (PGE(2)) 的升高。因此，我们研究了 COX-2 反应产物 PGE(2) 是否影响培养的大鼠皮质细胞中谷氨酸受体介导的细胞死亡。研究发现 PGE2 可以增强 NMDA 介导的细胞死亡。使用逆转录酶-聚合酶链式反应 (RT-PCR) 研究 EP1、EP2、EP3 和 EP4 PGE2 受体基因的转录。在皮质细胞中发现了 EP1、EP2 和 EP3 受体基因。布他前列素（一种 EP2 激动剂）显着增强 NMDA 介导的细胞死亡，而 17-苯基三去甲-PGE(2)（一种 EP1 激动剂）和磺前列酮（一种 EP3 激动剂）几乎没有作用。 PGE(2) 和布他前列素均升高皮质细胞中的 cAMP 水平；此外，毛喉素（一种腺苷酸环化酶激活剂）可增强 NMDA 介导的细胞死亡。这些结果表明，PGE(2) 通过 EP2 受体发挥作用，通过 cAMP 依赖性机制加剧兴奋性毒性神经变性。 (c) 2005 Elsevier Inc. 保留所有权利。
The activation of glutamate receptors, particularly N-methyl-D-aspartate (NMDA) receptors, initiates ischemic cascade in the early stages of cerebral ischemia. Postischemia, cerebral ischemia is also associated with an inflammatory reaction that contributes to tissue damage. The upregulation of neuronal cyclooxygenase-2 (COX-2) and elevation of prostaglandin E-2 (PGE(2)) have been reported to occur after cerebral ischemic insult. We therefore studied whether the COX-2 reaction product PGE(2) affects glutamate receptor-mediated cell death in cultured rat cortical cells. PGE2 was found to augment NMDA-mediated cell death. The transcription of EP1, EP2, EP3 and EP4 PGE2 receptor genes was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR). EP1, EP2 and EP3 receptor genes were found in cortical cells. Butaprost (an EP2 agonist) markedly enhanced NMDA-mediated cell death, whereas 17-phenyl trinor-PGE(2) (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect. Both PGE(2) and butaprost elevated cAMP intracellular levels in the cortical cells; moreover, forskolin, an activator of adenylate cyclase, enhanced NMDA-mediated cell death. These results suggest that PGE(2), acting via EP2 receptors, aggravates excitotoxic neurodegeneration by a cAMP-dependent mechanism. (c) 2005 Elsevier Inc. All rights reserved.