title: Role of ghrelin-induced cSrc activation in modulation of gastric mucosal inflammatory responses to Helicobacter pylori.
abstract: A peptide hormone, ghrelin, is recognized as an important modulator of gastric mucosal inflammatory responses to H. pylori through the regulation of nitric oxide synthase (NOS) system. As cSrc kinase plays a major role in transduction of signals that regulate the activity of NOS isozyme system, we investigated the influence of H. pylori LPS on the processes associated with Src activation in gastric mucosal cells. The LPS-induced drop in constitutive (c) cNOS activity and up-regulation in inducible (i) iNOS was associated with the suppression in cSrc kinase activity that was reflected in a decrease in its phosphorylation at Tyr⁴¹⁶. Further, the countering effect of ghrelin on the LPS-induced changes in cSrc activity and the extent of its phosphorylation was accompanied by a marked reduction in the activity of iNOS and an increase in cNOS activation through phosphorylation at Ser¹¹⁷⁹. Moreover, the effect of ghrelin on cSrc activation and its Tyr⁴¹⁶ phosphorylation was associated with the kinase S-nitrosylation that was susceptible to the blockage by cNOS inhibition. Our findings suggest that up-regulation in iNOS with H. pylori infection leads to disturbances in cNOS phosphorylation that exerts the detrimental effect on the processes of cSrc activation through cNOS-mediated S-nitrosylation. We also show that ghrelin attenuation of H. pylori-induced gastric mucosal inflammatory responses involves the enhancement in cSrc activation, elicited by the kinase S-nitrosylation and the increase in its phosphorylation at Tyr⁴¹⁶.
authors.affiliation: UMDNJ-NJ Dental School, Research Center C875, University of Medicine and Dentistry of New Jersey, 110 Bergen Street, PO Box 1709, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
authors.forename: B L
authors.initials: BL
authors.lastname: Slomiany
authors.forename: A
authors.initials: A
authors.lastname: Slomiany
mesh_terms: D000818:Animals; D045163:Antibodies, Phospho-Specific; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D054439:Ghrelin / Q000378:metabolism*; D016481:Helicobacter Infections / Q000276:immunology; D016480:Helicobacter pylori / Q000276:immunology*; D018928:Immunity, Mucosal; D008070:Lipopolysaccharides / Q000633:toxicity; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D015538:Nitrosation / Q000187:drug effects; D009994:Osmolar Concentration; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D045163:Antibodies, Phospho-Specific; D004791:Enzyme Inhibitors; D054439:Ghrelin; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D016392:Proto-Oncogene Proteins pp60(c-src)