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Insulin-like growth factor 1 protects human neuroblastoma cells SH-EP1 against MPP+-induced apoptosis by AKT/GSK-3β/JNK signaling

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Abstract

Parkinson’s disease (PD) is primarily caused by severe degeneration and loss of dopamine neurons in the substantia nigra pars compacta. Thus, preventing the death of dopaminergic neurons is thought to be a potential strategy to interfere with the development of PD. In the present work, we studied the effect of insulin-like growth factor-1 (IGF-1) on 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis in human neuroblastoma SH-EP1 cells. We found that the PI3K/AKT pathway plays a central role in IGF-mediated cell survival against MPP+ neurotoxicity. Furthermore, we demonstrated that the protective effect of AKT is largely dependent on the inactivation of GSK-3β, since inhibition of GSK-3β by its inhibitor, BIO, could mimic the protective effect of IGF-1 on MPP+-induced cell death in SH-EP1 cells. Interestingly, the IGF-1 potentiated PI3K/AKT activity is found to negatively regulate the JNK related apoptotic pathway and this negative regulation is further shown to be mediated by AKT-dependent GSK-3β inactivation. Thus, our results demonstrated that IGF-1 protects SH-EP1 cells from MPP+-induced apoptotic cell death via PI3K/AKT/GSK-3β pathway, which in turn inhibits MPP+-induced JNK activation.

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Acknowledgments

This research was supported by grant BMRC 05/1/33/19/412 from Biomedical Research Council of Singapore.

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  1. Genomics and Genetics Division, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore, 637551, Singapore

    Lei Wang, Hai-Jie Yang, Yin-Yan Xia & Zhi-Wei Feng

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Wang, L., Yang, HJ., Xia, YY. et al. Insulin-like growth factor 1 protects human neuroblastoma cells SH-EP1 against MPP+-induced apoptosis by AKT/GSK-3β/JNK signaling. Apoptosis 15, 1470–1479 (2010). https://doi.org/10.1007/s10495-010-0547-z

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