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

Biology

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