TOXICITY OF B-N-OXALYLAMINO-L-ALANINE ANDB-N-METHYLAMINO-L-ALANINE IN NIH3T3 CELLS IS MEDIATED BY INHIBITIONOF THE XC¯ ANTIPORTER

Risultato della ricerca: Other

Abstract

Beta-N-oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are two non-protein amino acids reported to induce neuronal degeneration. They have been involved in the pathogenesis of rare motor neuron diseases, as neurolathyrism or the ALS-Parkinson-Dementia complex of Guam. The mechanisms by which BOAA and BMAA toxicity is explicated is still unknown, but there is evidence that it might involve the inhibition of Xc¯ antiporter, that is the rate-limiting transporter of the synthesis of intracellular glutathione. In the present study, we investigated the mechanisms of BOAA and BMAA toxicity in the non-neuronal NIH3T3 cells. First, we treated NIH3T3 cells with BOAA or BMAA at different concentrations (1-10mM) and performed a cellular count after 0, 24, 48, 72 hours. We found that BOAA and BMAA induce toxicity in NIH3T3 cells in a dose-dependent manner. The strongest effect was seen after 24 hours with 10mM BOAA and after 48 hours in the cells treated with 10 mM BMAA. The toxic effect of both BOAA and BMAA is reduced if the cells are pre-incubated with cysteine 1mM. Immunoblot analysis of the xCT protein (i.e., the Xc¯ -specific subunit) showed that incubation of NIH3T3 cells with either BOAA or BMAA significantly decreased the protein level. Our results further confirm that the toxic effects of BOAA and BMAA are related to a decreased activity of the Xc¯ antiporter, thus impairing the cells' ability to activate the defenses against oxidative stress. These findings may contribute to our understanding of the role the oxidative stress in the pathophysiology of neurodegenerative disorders, such as Amyotrophic Lateral Sclerosis and Parkinson disease.
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2012

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