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Induction of motor neuron apoptosis by free 3‐nitro‐ l ‐tyrosine
Author(s) -
Peluffo Hugo,
Shacka John J.,
Ricart Karina,
Bisig C. Gaston,
MartìnezPalma Laura,
Pritsch Otto,
Kamaid Andrès,
Eiserich Jason P.,
Crow John P.,
Barbeito Luis,
Estèvez Alvaro G.
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2004.02363.x
Subject(s) - nitrotyrosine , peroxynitrite , motor neuron , glial fibrillary acidic protein , chemistry , tyrosine , astrocyte , programmed cell death , apoptosis , neuron , nitric oxide , biochemistry , microbiology and biotechnology , biology , superoxide , nitric oxide synthase , endocrinology , spinal cord , neuroscience , immunology , central nervous system , enzyme , immunohistochemistry
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.