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Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 expression in DRG neurons with excitotoxicity induced by glutamate in vitro.
Cell Mol Neurobiol. 2012 Mar; 32(2):191-200.CM

Abstract

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.

Authors+Show Affiliations

Department of Anatomy, Shandong University School of Medicine, Jinan, Shandong 250012, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21822733

Citation

Liu, Zhen, et al. "Activation of ERK1/2 and PI3K/Akt By IGF-1 On GAP-43 Expression in DRG Neurons With Excitotoxicity Induced By Glutamate in Vitro." Cellular and Molecular Neurobiology, vol. 32, no. 2, 2012, pp. 191-200.
Liu Z, Cai H, Zhang P, et al. Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 expression in DRG neurons with excitotoxicity induced by glutamate in vitro. Cell Mol Neurobiol. 2012;32(2):191-200.
Liu, Z., Cai, H., Zhang, P., Li, H., Liu, H., & Li, Z. (2012). Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 expression in DRG neurons with excitotoxicity induced by glutamate in vitro. Cellular and Molecular Neurobiology, 32(2), 191-200. https://doi.org/10.1007/s10571-011-9746-6
Liu Z, et al. Activation of ERK1/2 and PI3K/Akt By IGF-1 On GAP-43 Expression in DRG Neurons With Excitotoxicity Induced By Glutamate in Vitro. Cell Mol Neurobiol. 2012;32(2):191-200. PubMed PMID: 21822733.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of ERK1/2 and PI3K/Akt by IGF-1 on GAP-43 expression in DRG neurons with excitotoxicity induced by glutamate in vitro. AU - Liu,Zhen, AU - Cai,Heng, AU - Zhang,Ping, AU - Li,Hao, AU - Liu,Huaxiang, AU - Li,Zhenzhong, Y1 - 2011/08/06/ PY - 2011/04/21/received PY - 2011/07/28/accepted PY - 2011/8/9/entrez PY - 2011/8/9/pubmed PY - 2012/8/30/medline SP - 191 EP - 200 JF - Cellular and molecular neurobiology JO - Cell. Mol. Neurobiol. VL - 32 IS - 2 N2 - 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. SN - 1573-6830 UR - https://www.unboundmedicine.com/medline/citation/21822733/Activation_of_ERK1/2_and_PI3K/Akt_by_IGF_1_on_GAP_43_expression_in_DRG_neurons_with_excitotoxicity_induced_by_glutamate_in_vitro_ L2 - https://doi.org/10.1007/s10571-011-9746-6 DB - PRIME DP - Unbound Medicine ER -