Moreno-Ortega 2016 Neurotox Res
| Moreno-Ortega AJ, Al-Achbili LM, Alonso E, de Los RΓos C, GarcΓa AG, Ruiz-NuΓ±o A, Cano-Abad MF (2016) Neuroprotective effect of the novel compound ITH33/IQM9.21 against oxidative stress and Na+ and Ca2+ overload in motor neuron-like NSC-34 cells. Neurotox Res 30:380-91. |
Moreno-Ortega AJ, Al-Achbili LM, Alonso E, de Los Rios C, Garcia AG, Ruiz-Nuno A, Cano-Abad MF (2016) Neurotox Res
Abstract: Alternatives for the treatment of amyotrophic lateral sclerosis (ALS) are scarce and controversial. The etiology of neuronal vulnerability in ALS is being studied in motor neuron-like NSC-34 cells to determine the underlying mechanisms leading to selective loss of motor neurons. One such mechanism is associated with mitochondrial oxidative stress, Ca2+ overload, and low expression of Ca2+-buffering proteins. Therefore, in order to elicit neuronal death in ALS, NSC-34 cells were exposed to the following cytotoxic agents: (1) a mixture of oligomycin 10 Β΅M and rotenone 30 Β΅M (O/R), or (2) phenylarsine oxide 1 Β΅M (PAO) (to mimic excess free radical production during mitochondrial dysfunction), and (3) veratridine 100 Β΅M (VTD) (to induce overload of Na(+) and Ca2+ and to alter distribution of Ca2+-buffering proteins [parvalbumin and calbindin-D28k]). Thus, the aim of the study was to test the novel neuroprotective compound ITH33/IQM9.21 (ITH33) and to compare it with riluzole on in vitro models of neurotoxicity. Cell viability measured with MTT showed that only ITH33 protected against O/R at 3 ΞΌM and PAO at 10 ΞΌM, but not riluzole. ITH33 and riluzole were neuroprotective against VTD, blocked the maximum peak and the number of [Ca2+]c oscillations per cell, and restored the effect on parvalbumin. However, only riluzole reversed the effect on calbindin-D28k levels. Therefore, ITH33 was neuroprotective against oxidative stress and Na+/Ca2+ overload, both of which are involved in ALS. β’ Keywords: Amyotrophic lateral sclerosis, Ca2+, ITH33/IQ9.21, Mitochondria, NSC-34 cells, Veratridine
Labels: MiParea: Pharmacology;toxicology
Pathology: Cardiovascular
Organism: Mouse Tissue;cell: Nervous system
