RT Conference Proceedings
T1 Fingolimod phosphate protection against mitochondrial damage in neuronal cells
A1 Martín-Montañez, Elisa
A1 Gil Cebrián, Antonio Jesús
A1 Valverde, Nadia
A1 Lara, Estrella
A1 De Luque, Vanessa
A1 Boraldi, Federica
A1 Urbano, María
A1 García-Fernández, María Inmaculada
A1 Pavía-Molina, José
AB Background: Major role of oxidative stress in the pathogenesis of neurodegenerative diseases have been suggested, being mitochondria one of the main sources of ROS.Aim: In the present work, we have studied the antioxidant effect of fingolimod phosphate (FP) on neuronal mitochondrial function and morphology using a model of mitochondrial oxidative damage induced by menadione (Vitk3).Methods: SN4741 neuronal cells were grown (70-80% confluence) and used as control (non-treated cells) or treated cells with Vitk3 15 µM alone or in presence of  FP 50 nM during 4 hours. Mitochondrial membrane potential (MMP), cytochrome c oxidase (COX) activity, mitochondrial oxygen consumption rate (OCR), mitochondrial distribution (MTG) and morphology (EM) were analysed. Statistical differences were determined using one-way ANOVA.Results: Vitk3 incubation produces a dramatical decrease in MMP compared to control (43.7 %); this can be almost totally reverted by the co-incubation of Vitk3 in presence of FP (p<0.05). A 20.7 % decrease in COX activity has been found after Vitk3 incubation, again this effect was counteracted when Vitk3 and FP are combined, restoring COX activity to control levels (p<0.05). Vitk3 incubation triggers initially an increase in OCR, decreasing dramatically (61%) after 4 hours. In experiments co-incubating Vitk3 in presence of FP, the OCR decrease found was reduced to only 17% (p<0.05). In experiments with MitoTracker™ Green, we found a change in the network pattern distribution after Vitk3 administration that partially disappears when co-incubated in presence of FP. Almost all the mitochondria treated with Vitk3 show ultrastructural alterations at the electron microscopy level while normal mitochondria can be found when Vitk3 and FP are combined.Conclusion: FP protects against the mitochondrial damage induced by Vitk3, as seen by the results obtained in mitochondrial functional markers, distribution and morphology.
PB Elsevier
YR 2019
FD 2019-04-17
LK https://hdl.handle.net/10630/17896
UL https://hdl.handle.net/10630/17896
LA eng
NO Free Radic Biol Med. 2019 Jun;137:116-130. doi: 10.1016/j.freeradbiomed.2019.04.022
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.PS13/14: Study of the non-immunological mechanisms of action of Gilenya (Fingolimod) as therapeutic tool in Multiple Sclerosis and/or other neurodegenerative diseases. Novartis Farmacéutica S.A.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026