Cyclic guanosine 5′ monophosphate (GMP) prevents expression of neuronal nitric oxide synthase and apoptosis in motor neurons deprived of trophic factors in rats

• Published in: Neuroscience letters 2002-07, Vol.326 (3), p.201-205
• Main Authors: Estévez, Alvaro G, Kamaid, Andrés, Thompson, J.Anthony, Cornwell, Trudy L, Radi, Rafael, Barbeito, Luis, Beckman, Joseph S
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Brain derived trophic factor; Brain-Derived Neurotrophic Factor - pharmacology; Cells, Cultured; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Embryo, Mammalian; Free Radical Scavengers - toxicity; Fundamental and applied biological sciences. Psychology; Growth Substances - deficiency; Growth Substances - pharmacology; Immunohistochemistry; Isolated neuron and nerve. Neuroglia; Motor Neurons - drug effects; Motor Neurons - metabolism; Motor Neurons - pathology; Neuronal nitric oxide synthase; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide - toxicity; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase Type I; Nitrotyrosine; Peroxynitrite; Rats; Receptor, Nerve Growth Factor; Receptors, Nerve Growth Factor - antagonists & inhibitors; Spinal Cord - drug effects; Spinal Cord - metabolism; Tyrosine - analogs & derivatives; Tyrosine - biosynthesis; Tyrosine - drug effects; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/S0304-3940(02)00341-5

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 (