RT Journal Article
SR Electronic
T1 Nitric Oxide and Superoxide Contribute to Motor Neuron Apoptosis Induced by Trophic Factor Deprivation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 923
OP 931
DO 10.1523/JNEUROSCI.18-03-00923.1998
VO 18
IS 3
A1 Alvaro G. Estévez
A1 Nathan Spear
A1 S. Machelle Manuel
A1 Rafael Radi
A1 Christopher E. Henderson
A1 Luis Barbeito
A1 Joseph S. Beckman
YR 1998
UL http://www.jneurosci.org/content/18/3/923.abstract
AB 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 byl-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.