Induction of motor neuron apoptosis by free 3-nitro-L-tyrosine

Hugo Peluffo, John J. Shacka, Karina Ricart, C. Gaston Bisig, Laura Martìnez-Palma, Otto Pritsch, Andrès Kamaid, Jason P. Eiserich, John P. Crow, Luis Barbeito, Alvaro G. Estèvez

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Peroxynitrite-dependent tyrosine nitration has been postulated to be involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Evidence supporting this supposition includes the appearance of both free and protein-linked 3-nitro-L-tyrosine (nitrotyrosine) in both sporadic and familial ALS, as well as of increased free nitrotyrosine levels in the spinal cord of transgenic mice expressing ALS-linked superoxide dismutase mutants at symptom onset. Here we demonstrate that incubation with clinically relevant concentrations of nitrotyrosine induced apoptosis in motor neurons cultured with trophic factors. Nitrotyrosine was bound to proteins, but it was not incorporated into α-tubulin, as previously demonstrated for other cell types. Neither inhibition of nitric oxide production nor scavenging of superoxide and peroxynitrite prevented increases in cell nitrotyrosine immunoreactivity or motor neuron death, suggesting that these effects are not due to the endogenous formation of reactive nitrogen species. In contrast, some populations of astrocytes incorporated nitrotyrosine into α-tubulin, but free nitrotyrosine had no effect on the viability and phenotype of astrocytes in culture, as evaluated by glial fibrillary acidic protein immunoreactivity, cell growth and morphology. Co-culture of motor neurons on astrocyte monolayers delayed, but did not prevent, nitrotyrosine-induced motor neuron death. These results suggest that free nitrotyrosine may play a role in the induction of motor neuron apoptosis in ALS.

Original languageEnglish (US)
Pages (from-to)602-612
Number of pages11
JournalJournal of Neurochemistry
Volume89
Issue number3
StatePublished - May 2004

Keywords

  • Amyotrophic lateral sclerosis
  • Astrocytes
  • Nitric oxide
  • Peroxynitrite

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Peluffo, H., Shacka, J. J., Ricart, K., Bisig, C. G., Martìnez-Palma, L., Pritsch, O., Kamaid, A., Eiserich, J. P., Crow, J. P., Barbeito, L., & Estèvez, A. G. (2004). Induction of motor neuron apoptosis by free 3-nitro-L-tyrosine. Journal of Neurochemistry, 89(3), 602-612.