Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons
Joint Authors
Little, Peter J.
Xu, Jiangping
Feng, Zhong-Ping
Wang, Haitao
Zhao, Xia
Liu, Linlin
Zheng, Wenhua
Han, Chao
Zeng, Zhiwen
Quirion, Remi
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-08-12
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Glutamate-induced neurotoxicity is involved in various neuronal diseases, such as Alzheimer’s disease.
We have previously reported that glutamate attenuated the survival signaling of insulin-like growth factor-1 (IGF-1) by N-methyl-D-aspartate receptors (NMDARs) in cultured cortical neurons, which is viewed as a novel mechanism of glutamate-induced neurotoxicity.
However, the phosphorylation sites of IGF-1 receptor (IGF-1R) affected by glutamate remain to be elucidated, and importantly, which subtype of NMDARs plays a major role in attenuating the prosurvival effect of IGF-1 is still unknown.
In the present study, glutamate was found to attenuate the tyrosine phosphorylation of the IGF-1R and the prosurvival effect of IGF-1 in primary cultured cortical neurons.
NMDAR inhibitors, MK801 and AP-5, blocked the inhibitory effect of glutamate on the phosphorylation of IGF-1R and increased cell survival, while DNQX, LY341495, and CPCCOEt had no effect.
Interestingly, we found that glutamate decreased the phosphorylation of tyrosine residues 1131, 1135/1136, 1250/1251, and 1316, while it had no effect on tyrosine 950 in cortical neurons.
Moreover, using specific antagonists and siRNA to downregulate individual NMDAR subunits, we found that the activation of NR2B-containing NMDARs was essential for glutamate to inhibit IGF-1 signaling.
These findings indicate that the glutamate-induced attenuation of IGF-1 signaling is mediated by NR2B-containing NMDARs.
Our study also proposes a novel mechanism of altering neurotrophic factor signaling by the activation of NMDARs.
American Psychological Association (APA)
Zhao, Xia& Han, Chao& Zeng, Zhiwen& Liu, Linlin& Wang, Haitao& Xu, Jiangping…[et al.]. 2020. Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204759
Modern Language Association (MLA)
Zhao, Xia…[et al.]. Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1204759
American Medical Association (AMA)
Zhao, Xia& Han, Chao& Zeng, Zhiwen& Liu, Linlin& Wang, Haitao& Xu, Jiangping…[et al.]. Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1204759
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204759