Neuroprotective Effect of the Novel Compound ITH33/IQM9.21 Against Oxidative Stress and Na(+) and Ca(2+) Overload in Motor Neuron-like NSC-34 Cells
| Autor: | Ana Ruiz-Nuño, María F. Cano-Abad, Lamiaa Mouhid Al-achbili, Cristóbal de los Ríos, Antonio G. García, Elba Alonso, Ana J. Moreno-Ortega |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cell Survival Drug Evaluation Preclinical Mitochondrion Pharmacology Toxicology medicine.disease_cause Neuroprotection Arsenicals 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Glutamates Rotenone medicine Animals Phenylarsine oxide Motor Neurons Veratridine Riluzole General Neuroscience Amyotrophic Lateral Sclerosis Sodium Glutamate receptor Neurotoxicity medicine.disease Mitochondria Oxidative Stress 030104 developmental biology Neuroprotective Agents Parvalbumins nervous system chemistry Calbindin 1 Benzamides Calcium Oligomycins Neuroscience 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Neurotoxicity research. 30(3) |
| ISSN: | 1476-3524 |
| Popis: | 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, Ca(2+) overload, and low expression of Ca(2+)-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 µM and rotenone 30 µM (O/R), or (2) phenylarsine oxide 1 µM (PAO) (to mimic excess free radical production during mitochondrial dysfunction), and (3) veratridine 100 µM (VTD) (to induce overload of Na(+) and Ca(2+) and to alter distribution of Ca(2+)-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 μM and PAO at 10 μM, but not riluzole. ITH33 and riluzole were neuroprotective against VTD, blocked the maximum peak and the number of [Ca(2+)]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(+)/Ca(2+) overload, both of which are involved in ALS. |
| Databáze: | OpenAIRE |
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