Nitric oxide signaling

Grb-2 facilitates the transduction of an extracellular stimulus to an intracellular signaling pathway, (b) The adaptor protein PSD-95 associates through one of its three PDZ domains with the N-methyl-D-aspartic acid (NMDA) receptor. Another PDZ domain associates with a PDZ domain from neuronal nitric oxide synthase (nNOS). Through its interaction with PSD-95, nNOS is localized to the NMDA receptor. Stimulation by glutamate induces an influx of calcium, which activates nNOS, resulting in the production of nitric oxide. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Jung, H. W. Chung, Y. S. Kim, Y. S. Park, Y.-K. Celastrol inhibits production of nitric oxide and proinflammatory cytokines through MAPK signal transduction and NF-kB in LPS-stimulated BV-2 microglial cells. Exp. Mol. Med. 2007, 39, 715-721. 

Corasaniti MT, Bagetta G, Rotiroti D, Nistico G. The HIV envelope protein gpl20 in the nervous system interactions with nitric oxide, interleukin-1(3 and nerve growth factor signalling, with pathological implications in vivo and in vitro. Biochem Pharmacol 1998 56(2) 153-156. 

FIGURE 8.11 Multiple signal-transduction pathways initiated by calmodulin. Calmodulin bound to Ca2+ interacts and activates many enzymes, opening up a wide range of possible cellular responses. Abbreviations MAP-2, microtubule-associated protein 2 NO, nitric oxide Tau, tubulin assembly unit. 

Taking into account the electron density relocation (Table 2.4) two routes of NO adsorption can be distinguished. Thus, the nitric oxide coordinates to the monovalent Cr, Ni, and Cu ions in an oxidative way (A<2M > 0), whereas for the rest of the TMIs in a reductive way (AgM < 0). Although this classification is based on the rather simplified criteria, it is well substantiated by experimental observations. Examples of reductive adsorption are provided by interaction of NO with NinSi02 and NinZSM-5, leading at T > 200 K to a Ni -NOs+ adduct identified by the characteristic EPR signal [71]. At elevated temperatures, similar reduction takes place for ConZSM-5 [63], whereas in the case of Cu ZSM-5 part of the monovalent copper is oxidized by NO to Cu2+, as it can readily be inferred from IR and EPR spectra [72,73], This point is discussed in more detail elsewhere [4,57],... 

Developmental exposure to Pb or Mm affect signal transduction process, possibly related to the modulation of nitric oxide as well as alterations in receptor-mediated phosphoinositide hydrolysis and protein kinase C (rats)... 

NO is a gaseous neurotransmitter implicated in signaling in the central and peripheral nervous system as well as in the immune system and the vasculature. NO is formed from L-arginine by nitric oxide synthase (NOS). There are three isoforms of NOS. All isoforms require NADPH as a cofactor, use L-arginine as a substrate, and are inhibited by Nw-nitro-L-arginine methyl ester (L-NAME). The three isoforms are separate gene products. One isoform of NOS is a cytosolic, calcium/calmodulin-independent, inducible enzyme (iNOS). It is found in macrophages, neutrophils, vascular smooth muscle, and endothelia. The iNOS... 

Nitric oxide (NO) is an intercellular signaling molecule that can inhibit neuronal energy production (Brorson et al., 1999 Malefic et al., 2004). It has been found that NO donors cause large increases in extracellular adenosine in cultures of forebrain neurons (Rosenberg et al., 2000). These were shown to be caused by NO release, and the accumulation of adenosine was not blocked by probenecid (ENT blocker) or GMP (a blocker of AMP hydrolysis), suggesting that adenosine was likely of intracellular origin. Indeed, it was found that NO donors caused a decrease in intracellular ATP and the inhibition of adenosine kinase activity, possibly due to the rise in adenosine. 

At temperatures near 100° Horiguchi and associates (117) have shown that CO reacts with the superoxide ion on ZnO, but the Or spectrum remained at a fixed level following the addition of a mixture of CO and 02. Hydrogen did not react with 02- at that temperature. Upon addition of nitric oxide at room temperature the Oi signal instantaneously disappeared. 

L.J. Ignarro, Nitric-Oxide - A novel signal transduction mechanism for transcellular communication. 

G. Rocchitta, R. Migheli, M.P. Mura, G. Esposito, M.S. Desole, E. Miele, M. Miele, and P.A. Serra, Signalling pathways in the nitric oxide donor-induced dopamine release in the striatum of freely moving rats evidence that exogenous nitric oxide promotes Ca2+ entry through store-operated channels. Brain Res. 1023, 243-252 (2004). 

B. Beltran, M. Quintero, E. Garcia-Zaragoza, E. O Connor, J.V. Esplugues, and S. Moncada, Inhibition of mitochondrial respiration by endogenous nitric oxide a critical step in Fas signaling. Proc. Natl. Acad. Sci. U.S.A. 99, 8892 (2002). 

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