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

PELUFFO H, SHACKA JJ, RICART K, BISIG CG, MARTÌNEZ-PALMA L, PRITSCH O, KAMAID A, EISERICH JP, CROW JP, BARBEITO L, ESTÈVEZ AG.

JOURNAL OF NEUROCHEMISTRY

Año: 2004 vol. May p. 602 - 602

0022-3042

eroxynitrite-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 alpha-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 en