Modulation of gastric mucosal inflammatory responses to Helicobacter pylori by ghrelin: Role of cNOS-dependent IKK-β S-nitrosylation in the regulation of COX-2 activation

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dc.contributor.authorSlomiany, Bronislaw L.
dc.contributor.authorSlomiany, Amalia
dc.date.accessioned2016-10-24T12:04:26Z
dc.date.available2016-10-24T12:04:26Z
dc.date.issued2012-04
dc.description.abstractDisturbances in nitric oxide synthase (NOS) and cyclooxygenase (COX) isozyme systems, manifested by the excessive NO and prostaglandin (PGE2) generation, are well-recognized features of gastric mucosal inflammatory responses to H. pylori infection. In this study, we report that H. pylori LPS-induced enhancement in gastric mucosal inducible (i) iNOS expression and COX-2 activation was accompanied by the impairment in constitutive (c) cNOS phosphorylation, up-regulation in the inhibitory κB kinase-β (IKKβ) activation and the increase in the transcriptional factor, NF-κB, nuclear translocation. Further, we show that abrogation of cNOS control over NF-κB activation has lead to induction of iNOS expression and COX-2 activation through S-nitrosylation. Moreover, we demonstrate that the modulatory effect of peptide hormone, ghrelin, on the LPS-induced changes was reflected in the increase in Src/Akt-dependent cNOS activation through phosphorylation and the suppression of IKK-β activity through cNOS-mediated IKK-β protein S-nitrosylation. As a result, ghrelin exerted the inhibitory effect on NF-κB nuclear translocation, thus causing the repression of iNOS gene induction and the inhibition in COX-2 activation through iNOS-dependent S-nitrosylation. Our findings point to cNOS activation as a pivotal element in the signaling cascade by which ghrelin exerts modulatory control over proinflammatory events triggered in gastric mucosa by H. pylori infection.en_US
dc.identifier.citationAmerican Journal of Molecular Biology, 2012, 2, 113-123en_US
dc.identifier.urihttp://dx.doi.org/10.4236/ajmb.2012.22013
dc.identifier.urihttp://hdl.handle.net/123456789/998
dc.language.isoenen_US
dc.publisherScientific Research Publishingen_US
dc.subjectH. pylorien_US
dc.subjectGastric Mucosaen_US
dc.subjectiNOS Inductionen_US
dc.subjectCOX-2 Activationen_US
dc.subjectGhrelinen_US
dc.subjectcNOS Phosphorylationen_US
dc.subjectIKK-βen_US
dc.subjectS-Nitrosylationen_US
dc.titleModulation of gastric mucosal inflammatory responses to Helicobacter pylori by ghrelin: Role of cNOS-dependent IKK-β S-nitrosylation in the regulation of COX-2 activationen_US
dc.typeArticleen_US
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