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ERK和CREB信号通路在垂体腺苷酸环化酶激活肽对谷氨酸钠诱导的视网膜损伤的保护作用中的参与。

Involvement of ERK and CREB signaling pathways in the protective effect of PACAP in monosodium glutamate-induced retinal lesion.

作者信息

Rácz Boglarka, Tamás Andrea, Kiss Peter, Tóth Gabor, Gasz Balazs, Borsiczky Balazs, Ferencz Andrea, Gallyas Ferenc, Roth Erzsebet, Reglodi Dora

机构信息

Department of Surgical Research, University of Pécs, 7624 Pécs, Szigeti u 12. Hungary.

出版信息

Ann N Y Acad Sci. 2006 Jul;1070:507-11. doi: 10.1196/annals.1317.070.

DOI:10.1196/annals.1317.070
PMID:16891269
Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) has well-documented neuroprotective actions, which have also been shown in retinal degeneration induced by monosodium glutamate (MSG) in neonatal rats. The aim of this article was to investigate the activation of extracellular signal-regulated kinase (ERK1/2) and cyclic adenosine 3',5'-phosphate (cAMP)-responsive element binding protein (CREB) signaling pathways by Western blot analysis in retinal degeneration induced by MSG. We found that intravitreal administration of PACAP preceding the MSG treatments induced significant increases in the phosphorylation, that is, the activation of ERK1/2 and its downstream target, CREB, 12 h after the treatment compared to the contralateral untreated eye during the first two treatments, with no further elevations 24 h after treatments. These results demonstrate that the degenerative effect of MSG and the protective effect of PACAP involve complex kinase signaling pathways and are related to cAMP/ERK/CREB activation.

摘要

垂体腺苷酸环化酶激活多肽(PACAP)具有充分记载的神经保护作用,在新生大鼠中由谷氨酸钠(MSG)诱导的视网膜变性中也已得到证实。本文的目的是通过蛋白质印迹分析研究在MSG诱导的视网膜变性中细胞外信号调节激酶(ERK1/2)和环磷酸腺苷(cAMP)反应元件结合蛋白(CREB)信号通路的激活情况。我们发现,与前两次治疗期间对侧未治疗的眼睛相比,在MSG治疗前玻璃体内注射PACAP可导致治疗后12小时ERK1/2及其下游靶点CREB的磷酸化显著增加,即激活,治疗后24小时无进一步升高。这些结果表明,MSG的退行性作用和PACAP的保护作用涉及复杂的激酶信号通路,并且与cAMP/ERK/CREB激活有关。

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