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J Cell Physiol. 2019 Jan 8. doi: 10.1002/jcp.27774. [Epub ahead of print]

Small molecule of sphingosine as a rescue of dopaminergic cells: A cell therapy approach in neurodegenerative diseases therapeutics.

Author information

1
Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.
2
Pharmaceutical Sciences Research Center, Pharmaceutical Sciences Branch, Islamic Azad University Tehran Medical Unit, Tehran, Iran.
3
Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.
4
School of Medicine, Kashan University of Medical Sciences, Isfahan, Iran.
5
Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
6
Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
7
School of Advanced medical sciences, Stem Cell And Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Multiple sclerosis (MS) patients should take medication such as fingolimod (FTY-720) for a long time, hence pharmaceutical effects on other neural cells such as dopaminergic cells are important. Dopaminergic cell line, BE(2)-M17, was treated by FTY-720 and then cell viability and genes involve in neurosurvival were investigated. It was disclosed that FTY-720 significantly stimulates Bcl2 overexpression. Whereas, it decreased intracellular reactive oxygen species production and cell membrane damage of dopaminergic cells. The increase in Bcl2/Bax ratio increased the cell metabolic activity and decreased propidium iodide-positive cells. Besides, FTY-720 induced the overexpression of CACNA1C, nNOS gene, and nitric oxide production. However, FTY-720 induced GABARA1 overexpression and eventually it could overcame to the cytotoxic effect of intracellular calcium. This cascade led to tyrosine hydroxylase and BDNF genes overexpression whereas FTY-720 did not change GDNF concentration in BE(2)-M17 cells. Concluding, it might be said that taking FTY-720 in MS patients did not induce adverse effect on dopaminergic cells.

KEYWORDS:

FTY-720/ fingolimod; GDNF; MS patients; dopaminergic cells; neural survival

PMID:
30623407
DOI:
10.1002/jcp.27774

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