Neurotoxicity nitric oxide-mediated

Dawson, V.L., Dawson, T.M., London, E.D., Bredt, D.S. and Snyder, S.H. (1991). Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures. Proc. Natl Acad. Sci. USA 88, 6368-6371. 

Almeida A., Heales S. J., Bolanos J. P., and Medina J. M. (1998). Glutamate neurotoxicity is associated with nitric oxide-mediated mitochondrial dysfunction and glutathione depletion. Brain Res. 790 209-216. 

Gonzalez-Zulueta, M., Ensz, L.M., Mukhina, G., et al. 1998. Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediated neurotoxicity. J. Neurosci. 18(6) 2040-2055. 

D Apuzzo M, Relink A, Loetscher M, Hoxie JA, Clark-Lewis I, Melchers F, Baggiolini M, Moser B (1997) The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4. Eur J Immunol 27 1788-1793 Dawson VL, Dawson TM, Uhl GR, Snyder SH (1993) Human immunodeficiency virus type 1 coat protein neurotoxicity mediated by nitric oxide in primary cortical cultures. Proc Natl Acad Sci USA 90 3256-3259... 

In addition to nitric oxide, superoxide, and peroxynitrite, NO synthases are able to generate secondary free radicals because similar to cytochrome P-450 reductase, the reductase domain can transfer an electron from the heme to a xenobiotic. Thus it has been found [158,159] that neuronal NO synthase NOS I catalyzed the formation of CH3CH(OH) radical from ethanol. It was suggested that the perferryl complex of NOS I is responsible for the formation of such secondary radicals. Miller [160] also demonstrated that 1,3-dinitrobenzene mediated the formation of superoxide by nNOS. It was proposed that the enhancement of superoxide production in the presence of 1,3-dinitrobenzene converted nNOS into peroxynitrite-produced synthase and may be a mechanism of neurotoxicity of certain nitro compounds. 

Nitric Oxide Synthase in Neurotoxicity Mediated by Glutamate... 

Fig. 8.1 A schematic diagram illustrating the involvement of NF-k I in gpl20, ROS, NO, PG, IL-1/3 and TNF-a-mediated neurotoxicity. NMDA-R, N-Methyl-D-aspartate receptor, cPLA2, cytosolic phospholipase A2 lyso-PtdCho, lysophosphatidylcholine AA, arachidonic acid cAMP, cyclic adenosine monophosphate PKA, protein kinase A TNF-a, tumor necrosis factor-a TNF-a-R, TNF-a-receptor IL-1/8, interleukin-1 /3 IL-l/i-R, IL-1/8-receptor, IL-6, interleukin-6 MARK, mitogen-activated protein kinase NO, nitric oxide PG, prostaglandins EP-R, prostaglandin receptors NF-kB, nuclear factor-icB NF-kB-RE, nuclear factor-/cB-response element I/cB, inhibitory subunit of NF-icB HIV-1, human immunodeficiency virus type 1 gpl20, HIV-1 coat glycoprotein COX-2, cyclooxygenase-2 iNOS, inducible nitric oxide synthase SPLA2, secretory phospholipase A2 SOD, superoxide dismutase MMP, matrix metalloproteinase and VCAM-1, vascular adhesion molecule-1...

DOM treatment also rapidly decreases cellular GSH, which precedes neurotoxicity. This decrease is primarily due to DOM-mediated GSH efflux. DOM also induces an increase in oxidative stress as indicated by increases in ROS and lipid peroxidation products, which follow GSH efflux. Astrocytes from both genotypes are resistant to DOM-mediated neurotoxicity and present a diminished Ca2+ response to DOM-mediated toxicity (Walser et al., 2006). Exposure of neonatal rat microglia to DOM triggers the release of TNF-a and matrix metalloproteinase-9 (MMP-9) (Mayer et al., 2001). These molecules are involved in the modulation of neuroinflammation in brain (Farooqui et al., 2007). Collective evidence suggests that DOM-mediated neurodegeneration involves changes in cellular redox, oxidative stress, and increased expression of cytokines, nitric oxide synthase, NADPH diaphorase, and matrix metalloproteinase-9 (Walser et al., 2006 Chandrasekaran et al., 2004 Ananth et al., 2003a,b Mayer et al., 2001). 

Chao C, Hu S, Erlich L, Petersorr P (1995) Interleukiir-1 and tumor rrecrosis factor-alpha synergisdcally mediate neurotoxicity hrvolvemerrt of nitric oxide and of N-methyl-D-aspartale receptors. Brairr Behav hnmurr 9 355—365. 

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