H2O2 attenuates IGF-1R tyrosine phosphorylation and its survival signaling properties in neuronal cells via NR2B containing NMDA receptor | |
Zeng, Zhiwen1,2; Wang, Dejun1,3; Gaur, Uma1; Liao Rifang1; Wang, Haitao1; Zheng, Wenhua1![]() | |
2017-09-12 | |
Source Publication | ONCOTARGET
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ISSN | 1949-2553 |
Volume | 8Issue:39Pages:65313-65328 |
Abstract | Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200 mu M concentration which did not cause any significant toxicity to cells itself in our experiments. Moreover, studies using various glutamate receptor subtype antagonists displayed that N-methyl-D -aspartate (NMDA) receptor antagonist dizocilpine maleate (MK-801) blocked the effects of H2O2, whereas other glutamate receptor subtype antagonists, such as non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX), metabolic glutamate receptor antagonists LY341495 and CPCCOEt, had no effect. Further studies revealed that NR2B-containing NMDARs are responsible for these effects as its effects were blocked by pharmacological inhibitor Ro25-698 or specific siRNA for NR2B, but not NR2A. Finally, our data also showed that Ca2+ influx contributes to the effects of H2O2. Similar results were obtained in primary cultured cortical neurons. Taken together, the results from the present study suggested that H2O2 attenuated IGF-1R tyrosine phosphorylation and its survival signaling properties via NR2B containing NMDA receptors and Ca2+ influx in SH-SY5Y cells. Therefore, NMDAR antagonists, especially NR2B-selective ones, combined with IGF-1 may serve as an alternative therapeutic agent for oxidative stress related neurodegenerative disease. |
Keyword | H2o2 Sh-sy5y Nr2b Nmda Igf-1r |
DOI | 10.18632/oncotarget.18625 |
URL | View the original |
Indexed By | SCI |
Language | 英语 |
WOS Research Area | Oncology ; Cell Biology |
WOS Subject | Oncology ; Cell Biology |
WOS ID | WOS:000410291200052 |
Publisher | IMPACT JOURNALS LLC |
The Source to Article | WOS |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | Faculty of Health Sciences |
Affiliation | 1.Faculty of Health Sciences, University of Macau, Taipa, China 2.Shenzhen Mental Health Center and Shenzhen Kangning Hospital, Shenzhen, China 3.Department of Pharmacy, Qingdao Huangdao District People’s Hospital, Qingdao, China |
First Author Affilication | Faculty of Health Sciences |
Recommended Citation GB/T 7714 | Zeng, Zhiwen,Wang, Dejun,Gaur, Uma,et al. H2O2 attenuates IGF-1R tyrosine phosphorylation and its survival signaling properties in neuronal cells via NR2B containing NMDA receptor[J]. ONCOTARGET,2017,8(39):65313-65328. |
APA | Zeng, Zhiwen,Wang, Dejun,Gaur, Uma,Liao Rifang,Wang, Haitao,&Zheng, Wenhua.(2017).H2O2 attenuates IGF-1R tyrosine phosphorylation and its survival signaling properties in neuronal cells via NR2B containing NMDA receptor.ONCOTARGET,8(39),65313-65328. |
MLA | Zeng, Zhiwen,et al."H2O2 attenuates IGF-1R tyrosine phosphorylation and its survival signaling properties in neuronal cells via NR2B containing NMDA receptor".ONCOTARGET 8.39(2017):65313-65328. |
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