Induced nitrogen oxide synthase

Han HS, Qiao Y, Karabiyikoglu M, Giffard RG, Yenari MA. Influence of mild hypothermia on inducible nitric oxide synthase expression and reactive nitrogen production in experimental stroke and inflammation. J Neurosci 2002 22 3921-3928. 

Another central element of the Grishko hypothesis is the upregulation of inducible nitric oxide synthase (iNOS). Since the induction of iNOS is often associated with extensive nitric oxide formation, it is commonly a toxic event. However, nitric oxide formation is not detrimental in all cell types. Dimmeler et al. (1997) found that nitric oxide protects human endothelial cells against angiotensin II-mediated apoptosis. A key variable appears to be the amount of nitric oxide produced. In the cardiomyocyte, sufficient levels of nitric oxide are generated to cause the formation of toxic levels of peroxynitrite, while in endothelial cells, ROS, rather than reactive nitrogen species, appear to be the toxic mediators of apoptosis. 

Fig. 6.7 Interactions among exdtotoxidty, neuroinflammation, and oxidative stress following TBI. Plasma membrane (PM) Glutamate (Glu) phosphatidylcholine (PtdCho) cytosolic phospholipase A2 (CPLA2) lyso-phosphatidylchoUne (lyso-PtdCho) arachidonic acid (ARA) plateletactivating factor (PAF) secretory phospholipase A2 (SPLA2) reactive oxygen species (ROS) reactive nitrogen species (RNS) nitric oxide synthase (NOS) nuclear factor kB inhibited form (IkB/NFkB) nuclear factor KB-response element (NFkB-RE), inhibitory subunit of NFkB (IkB) tumor necrosis factor-a (TNF-a) interleukin-If (IL-lf ) interleukin-6 (IL-6) cyclooxygenase-2 (COX-2) lipoxygenase (LOX) peroxynitrite (ONOO ) inducible nitric oxide synthase (iNOS). Positive sign (+) indicates stimulation...

Nitrogen dioxide Nitro-arachidonic acid Cholesteryl nitro-linoleate Conjugated nitrolinoleic acid Nitro fatty acids Nitro-linoleic acid Nitro-oleic acid Nitric oxide synthase Inducible nitric oxide synthase... 

Nitric oxide ( NO) also contributes to the alveolar epithelium s oxidant burden, primarily as a result of the formation of reactive oxygen or nitrogen species. NO, one of the smallest and most distinctive biological mediators, is generated by nitric oxide synthase (NOS) which has three isoforms neuronal (nNOS, isoform I), inducible (iNOS, isoform II) and endothelial (eNOS, isoform III). nNOS and eNOS are constitutively expressed in cells and generate NO in small quantities for brief periods of time in response to increased intracellular CA2+ concentrations. It is currently unclear whether the level of expression or the enzymatic activity or either eNOS or nNOS is modulated by pathogens or inflammatory stimuli. 

Hinson JA, Bucci TJ, hwin LK, Michael SL, Mayeux PR (2002) Effect of inhibitors of nitric oxide synthase rat acetaminophen-induced hepatotoxicity in mice. Nitric Oxide 6 160-167 Hinson JA, Reid AB, McCullough SS, James LP (2004) Acetaminophen-induced hepatotoxicity role of metabolic activation, reactive oxygen/nitrogen species, and mitochondrial permeability transitimi. Drag Metab Rev 36 805—822... 

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