Damage of Neuroblastoma Cell SH-SY5Y Mediated by MPP+ Inhibits Proliferation of T-Cell Leukemia Jurkat by Co-Culture System

Abstract

The adaptive immune system has implications in pathology of Parkinson’s disease (PD). Research data demonstrated that the peripheral CD4+ T-cell population decreased in pathogenesis of PD. The effect of damaged dopaminergic neurons on peripheral T cells of PD is still unknown. In this study, we constructed a neuronal and glial cells co-culture model by using human neuroblastoma cells SH-SY5Y and gliomas cells U87. After the co-culture cells were treated with neurotoxin 1-methyl-4-phenylpyridinium (MPP+) for 24 h, the conditioned media was harvested and used to cultivate T-cell leukemia Jurkat cells for another 24 h. We then analyzed the cell proliferation, cell cycle and necrosis effect of Jurkat cells. The results showed that co-culture medium of SH-SY5Y and U87 cells with MPP+ treatment inhibited the proliferation of Jurkat cells compared to control medium without MPP+, even though the same concentration of MPP+ had very little toxicity to the Jurkat cell. Furthermore, co-culture medium with low concentration of MPP+ (100 µM) arrested Jurkat cells cycle in G2/M phase through increasing cell cycle division 2 (CDC2) and CyclinB1 expression level, whereas co-culture medium with high concentration of MPP+ (500 µM) induced Jurkat cell necrosis through cellular swelling and membrane breakage. Our data implies that damaged dopamine neurons with glial cells can lead to the reduced number or inhibited proliferation activity of peripheral T cells.

Comparative proteomics study of mitochondrial electron transport system modulation in SH-SY5Y cells following MPP+ versus 6-OHDA-induced neurodegeneration

“…Finally, FACS experiments confirmed that mitochondrial dysfunction and apoptosis were increased in 6-OHDA-and MPP+-treated SH-SY5Y cells (Fig. 1E, F), as reported in previous studies (Wang et al 2014;Chen et al 2021;Ganapathy et al 2016). These results indicate that neurodegeneration was induced in 6-OHDA-and MPP+-treated SH-SY5Y cells that simulated PD.…”

Carbon Ion Irradiated Neural Injury Induced the Peripheral Immune Effects in Vitro or in Vivo

“…Previous reports showed that neural cells injury could enhance peripheral immune T cells’ proliferation and decrease monocytes migration and invasion [ 7 , 8 , 9 , 10 , 11 ]. In order to evaluate the immune effect induced by heavy ion irradiation and to simulate the in situ condition of the brain, neuron-like SH-SY5Y cells and astrocytic glial U87 cells were cultured together as described previously [ 29 ] and then irradiated with carbon ions (1, 2, or 5 Gy). The medium was collected 24 h after irradiation and applied to immune cells (human leukemia monocytic cell line THP-1 and human leukemic T cell line Jurkat).…”

“…Toward the goal of assessing long-term immune responses to radiation, we have addressed the effects of heavy ion irradiation-induced neural cell damage on the peripheral immune system, which plays a key role in maintaining and modulating abscopal effects and systemic effects. We previously established an in vitro co-culture system to investigate neurotoxin-mediated regulation of the proliferation of peripheral immune cells [ 29 ]. In the present study, we examined the long-term effects on the peripheral immune system, including the peripheral blood, thymus, and spleen, after neural cell injury caused by carbon ion radiation in vitro and in vivo .…”

Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

“…A previous study showed that significant cell death of RA-differentiated cells was observed after 24 hours of exposure to 500 and 1000 μ M MPP + , and there was no apparent increase in the cell death by extending the exposure period to 48 hours [ 22 ]. For undifferentiated cells, studies showed that cell viability decreased to approximately 50% when cells were treated with 500 μ M MPP + for 24 hours [ 7 , 23 , 24 ]. Similarly, we observed significant cell death after 24-hour exposure of RA-differentiated cells as well as of undifferentiated cells to 250, 500, 1000, and 2000 μ M MPP + .…”