Nitric oxide: A pleiotropic signal in the nervous system

摘要: AD= : Alzheimer disease; cAMP= : cyclic adenosine monophosphate; cGMP= : guanosine CREB= : monophosphate response element-binding protein; DRG= : dorsal root ganglion; Drp-1= : dynamin-related protein 1; EET= : epoxyeicosatrienoic acid; eNOS= : endothelial nitric oxide synthase; FAD= : flavin adenine dinucleotide; FMN= : mononucleotide; GABA= : γ-aminobutyric GADPH= : glyceraldehyde-3-phophate dehydrogenase; HETE= : hydroxyeicosatetraenoic Hsp= : heat shock iNOS= : inducible MELAS= : mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes; MS= : multiple sclerosis; mtNOS= : variant of NOS; NADPH= : nicotinamide-adenine dinucleotide phosphate; NF-kB= : nuclear factor κB; NMDAR= : NMDA receptor; nNOS= : neuronal NO= : oxide; NOS= : PD= : Parkinson PKG= : kinase G; PNS= : peripheral nervous system; RNS= : reactive nitrogen species; SAH= : subarachnoid hemorrhage; SNO= : S-nitrosothiol; sGC= : soluble (cytosolic) guanylyl cyclase; VIP= : vasoactive intestinal polypeptide Nitric (NO) is a gaseous chemical transmitter that produced from the amino acid l-arginine by members NO synthase (NOS) family proteins. involved in several important functions CNS system (PNS), including modulation neurotransmission regulation local blood flow immune responses. interacts with intracellular targets to trigger signal transduction pathways. In CNS, participates synaptic plasticity, control sleep, body temperature, neurosecretion. PNS, mediates vasodilation relaxation visceral smooth muscle. However, when excess setting oxidative stress, becomes toxic, leading formation species (RNS), which cause cellular damage. These neurotoxic effects derivatives may be pathogenesis cerebral ischemia, inflammation, neoplasia, neurodegenerative disorders. There are comprehensive reviews on physiologic pathophysiologic roles system.1,–,12 ### Catalytic activity. The NOS enzymes catalyzes oxidation form l-citrulline (figure 1). dimeric enzyme; each monomer composed 2 distinct catalytic domains, an (NH2)-terminal oxygenase domain carboxy (COOH)-terminal reductase domain. The binding site for heme, oxygen (O2), tetrahydrobiopterin (BH4), l-arginine; binds (FAD), mononucleotide (FMN), reduced phosphate (NADPH). mechanism involves flavin-mediated electron transport NADPH heme center, where O2 incorporated into guanidine l-arginine, producing l-citrulline. Figure 1 General features signaling Nitric (NO*) arginine action presence (BH4) as …