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Salsolinol Damaged Neuroblastoma SH-SY5Y Cells Induce Proliferation of Human Monocyte THP-1 Cells Through the mTOR Pathway in a Co-culture System

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Abstract

Despite extensive efforts to study the inflammatory process in the central nervous system of Parkinson’s disease (PD) patients, little is known about the role of peripheral blood mononuclear cells (PBMCs) in PD. In the present study, we used an in vitro co-culture system to study the role of the human monocyte cell line THP-1 in medium conditioned by the neuroblastoma cell line SH-SY5Y damaged with the endogenous neurotoxin 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline (Salsolinol, Sal) in co-culture with the human glioma cell line U87. For this purpose, SH-SY5Y and U87 co-cultures were treated with Sal, and this conditioned medium containing mediators, including the potential effector CCL2, was isolated and applied to THP-1 cells. This treatment resulted in approximately 19 % cell proliferation as well as activation of mTOR and induction of phosphorylated 4E-BP1, S6K1, PI3K, and AKT proteins. Treatment with rapamycin, an mTOR inhibitor, attenuated the proliferation of THP-1 cells. U87 glial cells were essential for this as medium conditioned without them had no effect on THP-1 cells. These results suggest a positive effect of THP-1 cells on Sal-induced neurotoxicity in a cellular model of PD and this is likely mediated by the enhancement of cell proliferation through activation of the mTOR signaling pathway. Hence, PBMCs and their mTOR signaling pathway could be of therapeutic benefit in treating the endogenous neurotoxin-induced neuroinflammation in PD.

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Abbreviations

PD:

Parkinson’s disease

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Sal:

Salsolinol, 1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline

NMSal:

N-Methyl-salsolinol, 1,2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline

SNpc:

Substantia nigra pars compacta

FBS:

Fetal bovine serum

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Acknowledgments

We thank the National Natural Science Foundation of China (No. 31200636) and the ministry of Science and Technology, China (No. 2012YQ040140) for their support. We acknowledge the support provided by the Laboratory for Bioseparation and Bioanalysis and members in the lab.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. School of Life Science, Beijing Institute of Technology, 5 South Zhongguancun Street, Haidian District, Beijing, 100081, People’s Republic of China

    Fuli Wang, Junjun Ni, Xianghan Wang, Bingjie Xie, Chengcheng Feng, Sibo Zhao, Yasmeem Saeed, Hong Qing & Yulin Deng

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  1. Fuli Wang
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Correspondence to Yulin Deng.

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Wang, F., Ni, J., Wang, X. et al. Salsolinol Damaged Neuroblastoma SH-SY5Y Cells Induce Proliferation of Human Monocyte THP-1 Cells Through the mTOR Pathway in a Co-culture System. Neurochem Res 40, 932–941 (2015). https://doi.org/10.1007/s11064-015-1547-8

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  • DOI: https://doi.org/10.1007/s11064-015-1547-8

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