Biospin mediated signaling mechanisms in response to extmcellular stresses

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It is now recognized that nitric oxide (NO) is an endogenous mediator of vascular tone, a neurotransmitter in both the peripheral and central nervous systems, and an effector molecule in the immune system. NO is endogenously synthesized from L-arginine by NO synthases (NOSs), which exist in various organs and tissues in mammals. In the gastric mucosa, two types of constitutive NO synthases have been discovered and inducible NO synthase (iNOS), which is expressed in states of inflammation and immune activation, has not been detected in normal rat stomach. Additionally, a non-enzymatic NO production pathway appears to be active in the stomach, in which dietary nitrate is reduced to nitrite by the tongue surface bacteria and the nitrite is then carried into the stomach and reduced to NO under luminal acidic conditions. Endogenous NO, produced through these enzymatic and non-enzymatic pathways, has been demonstrated to be involved not only in the regulation of gastric mucosal blood flow, b … More ut also in the modulation of acid secretion, mucus secretion and gastric motility. In the present study, to elucidate physiological or pathophysiological roles of NO in stomach, we were carried out in vivo study by employing an animal model in which high concentration of NO were generated luminally at the gastro-esophageal junction by administration of nitrite plus acidic ascorbic acid, in vivo study on cross talk between iNOS and cyclooxygenase (COX) in rat gastric mucosa, and in vitro study on the effect of Helicobacter pylori (H. pylori)・lipopolysaccharide (LPS) on the expression of Toll-like receptor (TLR)2 and TLR4 using a mouse normal gastric epithelial cell line (GSM06). Consequently, we obtained following findings : 1) NO generated by nitrite administration on the lumen diffuses into the adjacent gastric tissue to a substantial degree, leading to localized consumption of glutathione in the tissue; 2) the effect of COX activity on iNOS-NO pathway can be important in the regulation of gastric mucosal integrity in inflammation states; 3) H. pylori-LPS stimulation induces TLR2 through TLR4 signaling in normal mouse gastric epithelial GSMO6 cells. This induced TLR2 cooperatively with TLR4 work for iNOS induction by H pylori-LPS simulation. Less