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The Journal of Neuroscience, February 1, 1998, 18(3):923-931
Nitric Oxide and Superoxide Contribute to Motor Neuron Apoptosis
Induced by Trophic Factor Deprivation
Alvaro G.
Estévez1, 4,
Nathan
Spear1, 4,
S.
Machelle
Manuel1, 4,
Rafael
Radi5,
Christopher E.
Henderson7,
Luis
Barbeito6, 8, and
Joseph S.
Beckman1, 2, 3, 4
Departments of 1 Anesthesiology,
2 Biochemistry and Molecular Genetics,
3 Neurobiology, and 4 The UAB Center for Free
Radical Biology, The University of Alabama at Birmingham, Birmingham,
Alabama 35233, 5 Departamento de Bioquímica,
Facultad de Medicina, and 6 Sección Neurociencias,
Facultad de Ciencias, Universidad de la República, Montevideo,
Uruguay 7 Institut National de la Santé et de la
Recherche Médicale (INSERM) Unité 382, Developmental
Biology Institute of Marseille (IBDM) (Centre National de la Recherche
Scientifique-INSERM-Université de la Mediterranée), 13288 Marseille Cedex 09, France, and 8 División
Neurobiología Celular y Molecular, Instituto Clemente Estable,
11600 Montevideo, Uruguay
Primary cultures of rat embryonic motor neurons deprived of
brain-derived neurotrophic factor (BDNF) induce neuronal nitric oxide
synthase (NOS) within 18 hr. Subsequently, >60% of the neurons undergo apoptosis between 18 and 24 hr after plating.
Nitro-L-arginine and nitro-L-arginine methyl
ester (L-NAME) prevented motor neuron death induced by
trophic factor deprivation. Exogenous generation of nitric oxide at
concentrations lower than 100 nM overcame the protection by
L-NAME. Manganese tetrakis (4-benzoyl acid) porphyrin, a
cell-permeant superoxide scavenger, also prevented nitric
oxide-dependent motor neuron death. Motor neurons cultured without
trophic support rapidly became immunoreactive for nitrotyrosine when
compared with motor neurons incubated with BDNF, L-NAME, or
manganese TBAP. Our results suggest that peroxynitrite, a strong
oxidant formed by the reaction of NO and superoxide, plays an important
role in the induction of apoptosis in motor neurons deprived of trophic factors and that BDNF supports motor neuron survival in part by preventing neuronal NOS expression.
Key words:
motor neuron; nitric oxide synthase; superoxide; peroxynitrite; nitrotyrosine; apoptosis; nitric oxide
Copyright © 1998 Society for Neuroscience 0270-6474/98/183923-09$05.00/0
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