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RGDS 四肽与大鼠海马体体外点燃:整合素介导生理稳定性的证据

RGDS tetrapeptide and hippocampal in vitro kindling in rats: evidence for integrin-mediated physiological stability.

作者信息

Grooms S Y, Jones L S

机构信息

Department of Neuroscience, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461, USA.

出版信息

Neurosci Lett. 1997 Aug 15;231(3):139-42. doi: 10.1016/s0304-3940(97)00524-7.

DOI:10.1016/s0304-3940(97)00524-7
PMID:9300641
Abstract

We have examined a potential role for integrins in an animal model of epileptogenesis termed in vitro kindling. Integrins mediate cell-cell and cell-matrix interactions, and also participate in the transduction of information from the extracellular environment to the intracellular milieu. As many extracellular matrix (ECM) molecules contain the conserved amino acid sequence arg-gly-asp-ser (RGDS) at the integrin recognition site, integrin-ECM binding can be disrupted using RGDS peptides. Hippocampal slices were washed in either RGDS, gly-gly-gly-gly (GGGG), vehicle or artificial cerebral spinal fluid (ACSF) for 1 h prior to in vitro kindling. Baseline electrophysiological responses were unaltered by RGDS peptide. The RGDS-treated slices displayed a significant decrease in the rate of spontaneous bursts, whereas the period of spontaneous bursting increased dramatically. Our results indicate that the competitive peptide, RGDS, changed hippocampal slice excitability over time, indicating that interference with ECM-integrin binding may alter neuronal signaling through an RGDS binding site.

摘要

我们在一种称为体外点燃的癫痫发生动物模型中研究了整合素的潜在作用。整合素介导细胞间和细胞与基质的相互作用,还参与从细胞外环境到细胞内环境的信息转导。由于许多细胞外基质(ECM)分子在整合素识别位点含有保守的氨基酸序列精氨酸-甘氨酸-天冬氨酸-丝氨酸(RGDS),因此可以使用RGDS肽破坏整合素与ECM的结合。在进行体外点燃之前,将海马切片在RGDS、甘氨酸-甘氨酸-甘氨酸-甘氨酸(GGGG)、溶剂或人工脑脊液(ACSF)中洗涤1小时。RGDS肽未改变基线电生理反应。经RGDS处理的切片自发爆发率显著降低,而自发爆发的时长则显著增加。我们的结果表明,竞争性肽RGDS随时间改变了海马切片的兴奋性,这表明干扰ECM与整合素的结合可能通过RGDS结合位点改变神经元信号传导。

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Integrins as receptor targets for neurological disorders.整合素作为神经紊乱的受体靶点。
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AMPA receptor stimulation increases alpha5beta1 integrin surface expression, adhesive function and signaling.
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J Neurochem. 2005 Jul;94(2):531-46. doi: 10.1111/j.1471-4159.2005.03203.x.
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Integrin subunit gene expression is regionally differentiated in adult brain.整合素亚基基因表达在成体大脑中呈区域分化。
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Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation.内源性丝氨酸蛋白酶抑制剂调节癫痫活动和海马体长期增强效应。
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