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Glutamate acting on N-methyl-D-aspartate receptors attenuates insulin-like growth factor-1 receptor tyrosine phosphorylation and Its survival signaling properties in rat hippocampal neurons
Zheng W.-H.3; Quirion R.3
2009-01-09
Source PublicationJournal of Biological Chemistry
ISSN00219258 1083351X
Volume284Issue:2Pages:855-861
Abstract

Impairing intracellular signaling induced by survival factors and excess glutamate have recently been suggested to play important role in neurodegenerative processes. However, the underlying mechanism(s) and interrelationships between these factors mostly remain to be established. In the present study, we show that glutamate attenuates the tyrosine phosphorylation of the insulin-like growth factor-1 (IGF-1) receptor and the survival effect of IGF-1 (100 nm) in hippocampal cultured neurons. Pretreatment of cultured hippocampal neurons with glutamate concentration dependently inhibited the tyrosine phosphorylation of IGF-1 receptors as well as that of IRS-1 and Shc, two IGF-1 receptor adapter proteins. The effect of glutamate was also evident on the phosphorylation of Akt, as well as its upstream kinase PI3K/PDK1 and downstream targets, GSK3β and FOXO3a. The inhibitory effect of glutamate (1 mm) was blocked by antagonists of the N-methyl-d-aspartate (NMDA) receptor, including MK801 (20 μm) and AP5 (100 μm), but not by blockers of other ionotropic or metabotropic glutamate receptor sub-types demonstrating the involvement of the NMDA receptor. This hypothesis is supported further by the observation that treatment with NMDA concentration dependently inhibited the activation and phosphorylation of IGF-1 receptors and downstream targets induced by IGF-1 (100 nm). These findings demonstrate that glutamate can block the effect of IGF-1 by decreasing IGF-1 receptor signaling and responsiveness, hence attenuating the survival properties of this trophic factor in neuronal cells. Our results also suggest a novel mechanism by which glutamate can reduce cell viability and induce neurotoxicity. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI10.1074/jbc.M807914200
URLView the original
Indexed BySCIE
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000262122900020
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Cited Times [WOS]:47   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Health University Institute
2.Sun Yat-Sen University
3.McGill University, Douglas Mental Health University Institute
Recommended Citation
GB/T 7714
Zheng W.-H.,Quirion R.. Glutamate acting on N-methyl-D-aspartate receptors attenuates insulin-like growth factor-1 receptor tyrosine phosphorylation and Its survival signaling properties in rat hippocampal neurons[J]. Journal of Biological Chemistry,2009,284(2):855-861.
APA Zheng W.-H.,&Quirion R..(2009).Glutamate acting on N-methyl-D-aspartate receptors attenuates insulin-like growth factor-1 receptor tyrosine phosphorylation and Its survival signaling properties in rat hippocampal neurons.Journal of Biological Chemistry,284(2),855-861.
MLA Zheng W.-H.,et al."Glutamate acting on N-methyl-D-aspartate receptors attenuates insulin-like growth factor-1 receptor tyrosine phosphorylation and Its survival signaling properties in rat hippocampal neurons".Journal of Biological Chemistry 284.2(2009):855-861.
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