Signal transduction nitric oxide

Figure 1 Nitric oxide signal transduction pathway. NO synthesized by NOS diffuses across cell membranes to a target cell. NO activates sGC, which leads to an increase in cCMP synthesis. The oxidation products of NO also can react with protein thiols, which leads to protein S-nitrosation.

Ding H, Demple B. Direct nitric oxide signal transduction via nitrosylation of iron-sulfur centers in the SoxR transcription activator. P. Natl. Acad. Sci. 2000 97 5146-5150. 

Baker PRS, Lin Y, Schopfer FJ, Woodcock SR, Groeger AL, Batthyany C, Swooney S, Long MH, lies KE, Baker LMS, Branchaud BP, Chen Y, Freeman BA. Fatty acid transduction of nitric oxide signaling Multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator-activated receptor ligands. J. Biol. Chem. 2005 280 42464-42475. 

Wright MM, Schopfer FJ, Baker PRS, Vidyasagar V, Powell P, Chumley P, lies KE, Freeman BA, Agarwal A. Fatty acid transduction of nitric oxide signaling Nitrolinoleic acid potently activates endothelial heme oxygenase 1 expression. Proc. Natl. Acad. Sci. U.S.A. 2006 103 4299-4304. 

Schopfer, F. J., P. R. Baker, G. Giles et al. 2005. Fatty acid transduction of nitric oxide signaling. Nitrohnoleic acid is a hydrophobicaUy stabilized nitric oxide donor. JBwlCjwm 280 (19) 19289-97. 

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. 

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. 

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)... 

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

This review will focus on three main reactions of dilute nitric oxide in physiological solutions. The first reaction is the binding of nitric oxide to ferrous heme iron of guanylate cyclase or other proteins, which is important for the activation of signal transduction pathways. 

Ignarro, L. J. (1991). Signal transduction mechanisms involving nitric oxide. Biochem. Pharmacol. 41, 485-490. 

Ignarro, L. J. (1990b). Nitric oxide A novel signal transduction mechanism for transcel-lular communication. Hypertension (Dallas) 16, 477-483. 

The signal transduction mechanisms triggered by binding of ET-1 to its vascular receptors include stimulation of phospholipase C, formation of inositol trisphosphate, and release of calcium from the endoplasmic reticulum, which results in vasoconstriction. Conversely, stimulation of PGI2 and nitric oxide synthesis results in decreased intracellular calcium concentration and vasodilation. 

Furthermore, the LPS signal transduction involves the activation of G proteins, of phospholipases C and D, the formation of diacyl-glycerol (DG) and inositol triphosphate (IP3). DG mediates the stimulation of protein kinase C (PKC) and IP3 induces an increase of cytosolic Ca++ The LPS signaling pathway also involves tyrosine kinases, constitutive nitric oxide (NO) synthase (cNOS), cGMP-dependent protein kinase, Ca channels, calmodulin and calmodulin kinase [27,28], as well as the MAP kinases [29] ERK1, ERK2 and p38 [23], The intracellular events in response to LPS are due to lipid A because they are inhibited by polymyxin B which is known to bind lipid A [27] and they are reproduced by lipids A [30,31]. 

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