Ag. Estevez et al., NITRIC-OXIDE AND SUPEROXIDE CONTRIBUTE TO MOTOR-NEURON APOPTOSIS INDUCED BY TROPHIC FACTOR DEPRIVATION, The Journal of neuroscience, 18(3), 1998, pp. 923-931
Primary cultures of rat embryonic motor neurons deprived of brain-deri
ved 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-argi
nine methyl ester (L-NAME) prevented motor neuron death induced by tro
phic factor deprivation. Exogenous generation of nitric oxide at conce
ntrations lower than 100 nM overcame the protection by L-NAME. Mangane
se tetrakis (4-benzoyl acid) porphyrin, a cell-permeant superoxide sca
venger, also prevented nitric oxide-dependent motor neuron death. Moto
r neurons cultured without trophic support rapidly became immunoreacti
ve for nitrotyrosine when compared with motor neurons incubated with B
DNF, 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 depri
ved of trophic factors and that BDNF supports motor neuron survival in
part by preventing neuronal NOS expression.