标题:Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 expression in DRG neurons with excitotoxicity induced by glutamate in vitro.
作者:Zhen Liu;Heng Cai;Ping Zhang;Hao Li;Huaxiang Liu;Zhenzhong Li
作者机构:[Liu, Z] Department of Anatomy, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan, Shandong 250012, China;[ Cai, H] Department of Histo 更多
通讯作者:Li, ZZ
通讯作者地址:[Li, ZZ]Shandong Univ, Sch Med, Dept Anat, 44 Wenhua Xi Rd, Jinan 250012, Shandong, Peoples R China.
来源:Cellular and Molecular Neurobiology
出版年:2012
卷:32
期:2
页码:191-200
DOI:10.1007/s10571-011-9746-6
关键词:Insulin-like growth factor-1; Glutamate; Growth-associated protein-43;; ERK1/2; PI3K; Akt; Dorsal root ganglion
摘要:Insulin-like growth factor-1 (IGF-1) is a neurotrophic factor and plays an important role in promoting axonal growth from dorsal root ganglion (DRG) neurons. Whether IGF-1 influences growth-associated protein 43 (GAP-43) expression and activates the extracellular signal-regulated protein kinase (ERK1/2) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in DRG neurons with excitotoxicity induced by glutamate (Glu) remains unknown. In this study, embryonic 15-day-old rat DRG explants were cultured for 48 h and then exposed to IGF-1, Glu, Glu + IGF-1, Glu + IGF-1 + PD98059, Glu + IGF-1 + LY294002, Glu + IGF-1 + PD98059 + LY294002 for additional 12 h. The DRG explants were continuously exposed to growth media as control. The levels of GAP-43 mRNA were detected by real time-PCR analysis. The protein levels of GAP-43, phosphorylated ERK1/2, phosphorylated Akt, total ERK1/2, and total Akt were detected by Western blot assay. GAP-43 expression in situ was determined by immunofluorescent labeling. Apoptotic cell death was monitored by Hoechst 33342 staining. IGF-1 alone increased GAP-43 and its mRNA levels in the absence of Glu. The decreased GAP-43 and its mRNA levels caused by Glu could be partially reversed by the presence of IGF-1. IGF-1 rescued neuronal cell death caused by Glu. Neither the ERK1/2 inhibitor PD98059 nor the PI3K inhibitor LY294002 blocked the effect of IGF-1, but both inhibitors together were effective. To validate the impact of GAP-43 expression by IGF-1, GAP-43 induction was blocked by administration of dexamethasone (DEX). IGF-1 partially rescued the decrease of GAP-43 and its mRNA levels induced by DEX. DEX induced an increase of cell apoptosis. IGF-1 may play an important role in neuroprotective effects on DRG neurons through regulating GAP-43 expression with excitotoxicity induced by Glu and the process was involved in both ERK1/2 and PI3K/Akt signaling pathways.
收录类别:SCOPUS;SCIE
WOS核心被引频次:25
Scopus被引频次:24
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84864663005&doi=10.1007%2fs10571-011-9746-6&partnerID=40&md5=186b385e349877e0e537cf5c488814be
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