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兴奋性氨基酸诱导的穆勒胶质细胞中AP-1 DNA结合活性

Excitatory amino acid-induced AP-1 DNA binding activity in Müller glia.

作者信息

López-Colomé A M, Murbartián J, Ortega A

机构信息

Instituto de Fisiología Celular-UNAM, Mexico.

出版信息

J Neurosci Res. 1995 Jun 1;41(2):179-84. doi: 10.1002/jnr.490410205.

Abstract

The effect of L-glutamate (L-Glu) and its structural analogs N-methyl-D-aspartate (NMDA), quisqualate (QA), and kainate (KA) on the DNA binding activity of the Activator Protein 1 (AP-1) and the Ca2+/cAMP Responsive Element Binding Protein (CREB) families of transcription factors was examined in cultured chick retinal Müller glia cells. L-Glu, NMDA, and KA evoked a dose and time dependent increase in AP-1 DNA binding activity and had no effect on CREB binding. The order of potency for stimulating AP-1 DNA binding was NMDA > or = Glu > KA >> QA. L-Glu responses were partially blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and by 3-[RS)-2-carboxypiperazin-4-yl)]-propyl-1-phosphonate (CPP) indicating that the increase in DNA binding is mediated both by an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/low affinity KA and a NMDA subtypes of L-Glu receptors. Since Müller glia L-Glu receptors are probably mediators of the efficacy of the excitatory transmission in the retina, the present findings suggest that a stimulus-transcription coupling triggered by L-Glu in the glial cells might have a role in the long-term modulation of these synapses.

摘要

在培养的鸡视网膜 Müller 胶质细胞中,研究了 L-谷氨酸(L-Glu)及其结构类似物 N-甲基-D-天冬氨酸(NMDA)、quisqualate(QA)和红藻氨酸(KA)对激活蛋白 1(AP-1)和转录因子 Ca2+/cAMP 反应元件结合蛋白(CREB)家族的 DNA 结合活性的影响。L-Glu、NMDA 和 KA 引起 AP-1 DNA 结合活性呈剂量和时间依赖性增加,而对 CREB 结合无影响。刺激 AP-1 DNA 结合的效力顺序为 NMDA≥Glu>KA>>QA。L-Glu 的反应被 6-氰基-7-硝基喹喔啉-2,3-二酮(CNQX)和 3-[(RS)-2-羧基哌嗪-4-基]-丙基-1-膦酸酯(CPP)部分阻断,表明 DNA 结合的增加是由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)/低亲和力 KA 和 L-Glu 受体的 NMDA 亚型介导的。由于 Müller 胶质细胞的 L-Glu 受体可能是视网膜中兴奋性传递效能的介质,目前的研究结果表明,L-Glu 在胶质细胞中触发的刺激-转录偶联可能在这些突触的长期调节中起作用。

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