Cyclic guanosine 5' monophosphate (GMP) prevents expression of neuronal nitric oxide synthase and apoptosis in motor neurons deprived of trophic factors in rats.
Deprivation of trophic factors induces expression of neuronal nitric oxide synthase (NOS) and nitric oxide production in cultured motor neurons, leading to apoptosis. Motor neuron apoptosis requires the simultaneous production of nitric oxide and superoxide and is associated with increased nitrotyrosine immunoreactivity. Nitric oxide also stimulates cyclic guanosine 5' monophosphate (cGMP) synthesis, which enhances the survival of motor neurons treated with brain derived trophic factor (BDNF). Here we report that cGMP analogs blocked neuronal NOS induction, nitrotyrosine accumulation, and prevented apoptosis for up to 3 day of motor neurons deprived of trophic factors. Low concentrations of exogenous nitric oxide (<100 nM), which are not toxic for BDNF-treated cultures, reversed the protective effect of cGMP. These results suggest that elevation of cGMP could decrease nitric oxide production, and thereby preventing motor neuron apoptosis.
Estévez
Alvaro G
AG
Department of Physiology and Biophysics, University of Alabama at Birmingham, 1918 University Boulevard, MCLM 850, Birmingham, AL 35294-0005, USA. aestevez@uab.edu
Kamaid
Andrés
A
Thompson
J Anthony
JA
Cornwell
Trudy L
TL
Radi
Rafael
R
Barbeito
Luis
L
Beckman
Joseph S
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology*; D004622:Embryo, Mammalian; D016166:Free Radical Scavengers / Q000633:toxicity; D006133:Growth Substances / Q000172:deficiency* / Q000494:pharmacology; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism* / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000187:drug effects; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D016166:Free Radical Scavengers; D006133:Growth Substances; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006152:Cyclic GMP