Inducible NO synthase

Inducible NO synthase (iNOS) is usually not constitutively expressed, but can be induced in macrophages by bacterial lipopolysaccharide (LPS), cytokines and other-agents. Although primarily identified in macrophages, expression of the enzyme can be stimulated in virtually any cell or tissue, provided the appropriate inducing agents have been identified (for review see [1] and [3]). 

Red wine contains quercetin, rutin, catechin, and epicatechin, among other flavonoids (Frankel and others 1993). Quercetin and other phenolic compounds isolated from wines were found to be more effective than a-tocopherol in inhibiting copper-catalyzed LDL oxidation. It has been determined that quercetin has also several anti-inflammatory effects it inhibits inflammatory cytokine production (Boots and others 2008), inducible NO synthase expression and activation of inflammatory transcription factors (Hamalainen and others 2007), and activity of cyclooxygenase and lipooxygenase (Issa 2006), among others. 

Free radicals are supposed to have a significant role in the progression of acute pancreatitis. The involvement of free radicals was firstly demonstrated in many animal models [355,356], Later on, it has been shown that the levels of superoxide and lipid peroxides increased in the blood from patients with acute pancreatitis [357], Rahman et al. [358] found enhanced urinary nitrite excretion in patients with severe acute pacreatitis. It was suggested that this fact is not simply a reflection of systemic inflammation but probably a consequence of the endotoxin-mediated upregulation of inducible NO synthase. 

Before discussing some of the observations concerning -NO in our laboratory, it is important to review a few of the basic principles of "NO production and mechanism of action. More detail on these topics can be found in other chapters in this book. First, "NO production can occur by one of two categories of NOS enzymes. Constitutive enzymes are expressed in various cell types, including endothelial cells, neurons, and neutrophils. Production of "NO by this type of enzyme is typically calcium/calmodulin-dependent and occurs immediately. This type of production has also been referred to as low output. Cells such as macrophages, hepatocytes, and smooth muscle cells express an inducible NO synthase. The induction of this enzyme typically results from exposure of the cells... 

Rodent KC and HC, as well as human HC, express an inducible NO synthase under septic or inflammatory conditions. In vivo in endotoxemia, this expression is transient. Our in vivo data indicate that this induced -NO serves a protective role in the liver and reduces hepatic injury in endotoxemia. This protective action may be mediated by the capacity of NO to neutralize oxygen radicals and prevent platelet adherence and aggregation. Our in vitro studies show that HC-derived -NO can activate soluble guanylate cyclase. Other in vitro effects include the nonspecific suppression of protein synthesis and a small reduction in mitochondrial aconitase activity. The relevance of these in vitro actions to hepatic function in vivo remains to be determined. 

Noiri, E., Peresleni, T., Miller, F. and Goligorsky, M. S. (1996). In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J. Clin. Invest. 97, 2377-2383. 

Le Cras, T.D., Xue, C., Rengasamy, A., and Johns, R.A. 1996. Chronic hypoxia up regulates endothelial and inducible NO synthase gene and protein expression in rat lung. Am. J. Physiol. 270 L164-L170. 

Despite the small stability constant, CO has been shown to be involved in deactivating inducible NO synthase, K 0.003 pM-1 [34] and activates guanylyl cyclase, K 0.004 pM 1 [35]. However, many biological studies have shown that... 

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