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.
© 2019 Wiley Periodicals, Inc.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Calcium Channels, L-Type / genetics
-
Calcium Channels, L-Type / metabolism
-
Cell Line
-
Cell Survival
-
Dopaminergic Neurons / metabolism*
-
Fingolimod Hydrochloride / pharmacology*
-
Gene Expression Regulation / drug effects
-
Glial Cell Line-Derived Neurotrophic Factor / genetics
-
Glial Cell Line-Derived Neurotrophic Factor / metabolism
-
Humans
-
Immunosuppressive Agents / pharmacology
-
L-Lactate Dehydrogenase / metabolism
-
Nitric Oxide / metabolism
-
Propidium
-
Proto-Oncogene Proteins c-bcl-2 / genetics
-
Proto-Oncogene Proteins c-bcl-2 / metabolism
-
Reactive Oxygen Species
-
Receptors, GABA-A / genetics
-
Receptors, GABA-A / metabolism
-
Sphingosine / metabolism*
-
Tyrosine 3-Monooxygenase / genetics
-
Tyrosine 3-Monooxygenase / metabolism
-
bcl-2-Associated X Protein / genetics
-
bcl-2-Associated X Protein / metabolism
Substances
-
BAX protein, human
-
BCL2 protein, human
-
CACNA1C protein, human
-
Calcium Channels, L-Type
-
GABRA1 protein, human
-
Glial Cell Line-Derived Neurotrophic Factor
-
Immunosuppressive Agents
-
Proto-Oncogene Proteins c-bcl-2
-
Reactive Oxygen Species
-
Receptors, GABA-A
-
bcl-2-Associated X Protein
-
Nitric Oxide
-
Propidium
-
L-Lactate Dehydrogenase
-
Tyrosine 3-Monooxygenase
-
Fingolimod Hydrochloride
-
Sphingosine