Inducible nitric oxide synthase iNOS

Nitric oxide synthase The dual role of nitric oxide (NO) and the enz)mies that produce it (nitric oxide synthases, NOSs, iNOS inducible, eNOS endothelial, and nNOS neuronal) on tumor growth and metastasis has been investigated in several cancer models. Whether nitric oxide is beneficial or deleterious in human neoplasias seems to be organ- and cell-specific, and depends on many factors including redox status. The NO/NOS pathway represents an alternative mode of action for polyphenols since it has been shown that they can interact with this pathway in many different ways, summarized below. 

Secretory leukocyte inhibitory protein (SLPI) Inducible nitric oxide synthase (iNOS)... 

Three isoforms of NO synthesizing enzymes ( nitric oxide synthase (NOS)) were isolated, purified, and cloned neuronal NO synthase ( neuronal nitric oxide synthase (nNOS) or isoform (I), immunological or inducible NOS ( inducible (immunological) nitric oxide synthase (iNOS) or isoform (II), and endothelial NOS ( endothelial nitric oxide synthase (eNOS) or isoform... 

Nitric oxide has also been implicated in PD. Thus animals with MPTP-induced Parkinsonism not only show extensive gliosis in the substantia nigra (like humans) in which the glial cells produce NO, but Liberatore and colleagues have found that in iNOS (inducible nitric oxide synthase) knock-out mice the toxicity of MPTP is halved. Since NO releases iron from ferritin and produces toxic peroxinitrate in the presence of superoxide radicals it could accelerate, even if it does not initiate, dopaminergic cell death (see Hirsch and Hunot 2000 for further details). 

Hong CH, Sun KH, Jin O, Sun SK, Kyung AN, Sang KL. Evaluation of natural products on inhibition of inducible cyclooxygenase (COX-2) and nitric oxide synthase (iNOS) in cultured mouse macrophage cells. J Ethnopharmacol 2002 83 153-159. 

Rafi, MM and Shafaie, Y, 2007. Dietary lutein modulates inducible nitric oxide synthase (iNOS) gene and protein expression in mouse macrophage cells (RAW 264.7). Mol Nutr Food Res 51, 333-340. 

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 is widely distributed and at least three isoenzymes of nitric oxide synthase (NOS) have been described iNOS (inducible), eNOS (endothelial) and nNOS (neuronal). The substrate for NOS is the amino acid arginine ... 

As shown in Figure 5.5, nitric oxide is synthesized from the amino acid arginine under the influence of nitric oxide synthase (NOS). This enzyme exists in several tissues as either a constitutive or inducible protein (iNOS). 

Figure 6. Comparative gene expression ratios in ARF kidneys of MSC- and vehicle-treated animals. Data were generated by referencing each gene to p-actin as internal control. A MSC treatment cansed significant (P < 0.05) suppression (> 10 fold) of proinflammatory IL-ip, TNF a, and IFN-y (above bars actnal valnes). Anti-inflammatory lL-10 was robustly expressed in MSC-and not in vehicle treated animals. Filled bars on all panels depict gene expression ratio of 1, i.e., a value obtained when gene expression ratios between MSC- and vehicle-treated animals are "equal. B MSC treatment cansed increased gene expression of bFGF and TGF-a, whereas that of HGF was suppressed. C antiapoptotic Bcl-2 expression was robnstly indnced, whereas that of inducible nitric oxide synthase (iNOS) was snppressed in MSC- vs. vehicle-treated animals. eNOS, endothelial NOS.

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

Chiou WF, Chen CF, Lin JJ. (2000) Mechanism of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide. Br J Pharmacol 129 1553-1560. 

Noiri et al. used AS-ODN to inhibit production of inducible nitric oxide synthase (INOS) in an attempt to prevent NO production in an ischaemic kidney. A single intravenous injection of iNOS AS-ODN attenuated acute renal failure and reduced the morphological abnormalities [129],... 

To set up and validate the in vitro systems we initiated a study with rat Uver slices. Stimulation by Upopolysaccharide (LPS) in liver slices was used to evoke a pro-inflammatory response in the Uver. Lipopolysaccharide (LPS), a component of Gram-negative bacterial ceU walls (also called endotoxin), has been associated with tissue injury and sepsis. In the Uver LPS activates the resident macrophages, the Kupffer ceUs, which results in cytokine release [96]. Furthermore, LPS is cleared by the Uver, mainly by Kupffer ceUs [97]. One of the major features of endotoxic shock is the induction of nitric oxide S5mthase in the Uver [98]. Inducible nitric oxide synthase (iNOS), the expression of which is induced by LPS and cytokines, produces nitric oxide (NO) in large quantities [99]. 

---