| Residential College | true |
| Status | 已發表Published |
| Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons | |
Xia Zhao1; Chao Han2; Zhiwen Zeng1; Linlin Liu1; Haitao Wang3 ; Jiangping Xu3; Zhong-Ping Feng4; Peter J. Little5; Remi Quirion6; Wenhua Zheng1
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| 2020-08-11 | |
| Source Publication | Oxidative Medicine and Cellular Longevity
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| ISSN | 1942-0900 |
| Volume | 2020 |
| Abstract | 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. |
| DOI | 10.1155/2020/5173184 |
| URL | View the original |
| Indexed By | SCIE |
| Language | 英語English |
| WOS Research Area | Cell Biology |
| WOS Subject | Cell Biology |
| WOS ID | WOS:000563532700001 |
| The Source to Article | PB_Publication |
| Scopus ID | 2-s2.0-85089979639 |
| Fulltext Access | |
| Citation statistics | |
| Document Type | Journal article |
| Collection | Faculty of Health Sciences DEPARTMENT OF PHARMACEUTICAL SCIENCES |
| Corresponding Author | Haitao Wang; Wenhua Zheng |
| Affiliation | 1.Faculty of Health Sciences, University of Macau, Taipa, Macau, China 2.State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center and School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China 3.School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China 4.Faculty of Medical Sciences, University of Toronto, Toronto, Canada 5.School of Pharmacy, Pharmacy Australia Centre of Excellence (PACE), The University of Queensland, 20 Cornwall St., Woolloongabba, QLD 4102, Australia 6.Douglas Hospital Research Center, McGill University, Montreal, Canada |
| First Author Affilication | Faculty of Health Sciences |
| Corresponding Author Affilication | Faculty of Health Sciences |
| Recommended Citation GB/T 7714 | Xia Zhao,Chao Han,Zhiwen Zeng,et al. Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons[J]. Oxidative Medicine and Cellular Longevity, 2020, 2020. |
| APA | Xia Zhao., Chao Han., Zhiwen Zeng., Linlin Liu., Haitao Wang., Jiangping Xu., Zhong-Ping Feng., Peter J. Little., Remi Quirion., & Wenhua Zheng (2020). Glutamate Attenuates the Survival Property of IGFR through NR2B Containing N-Methyl-D-aspartate Receptors in Cortical Neurons. Oxidative Medicine and Cellular Longevity, 2020. |
| MLA | Xia Zhao,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(2020). |
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