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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 PublicationONCOTARGET
ISSN1949-2553
Volume8Issue: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.

KeywordH2o2 Sh-sy5y Nr2b Nmda Igf-1r
DOI10.18632/oncotarget.18625
URLView the original
Indexed BySCI
Language英语
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000410291200052
PublisherIMPACT JOURNALS LLC
The Source to ArticleWOS
Fulltext Access
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.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 AffilicationFaculty 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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