Author(s)

Bronislaw L. Slomiany, Amalia Slomiany

Research Center, Rutgers School of Dental Medicine, Rutgers, The State University of New Jersey, Newark, USA.

Disturbances in constitutive nitric oxide synthase (cNOS) activation associated with H. pylori colonization of gastric mucosa are considered of major consequences in defining the extent of inflammatory involvement. As rapid changes in cNOS activation are linked to the enzyme phosphorylation at the specific Ser/Thr residues, we investigated the influence of H. pylori LPS and gastric hormone, ghrelin, on the processes of phosphorylation of these two critical sites in gastric mucosal cells. We show that the LPS-induced reduction in cNOS activity is reflected in the phosphorylation on Thr⁴⁹⁷, while the countering effect of ghrelin is associated with a rapid increase in cNOS phosphorylation on Ser1179. Further, we demonstrate that cNOS phosphorylation on Thr⁴⁹⁷ as well as Ser¹¹⁷⁹ displays dependence on PKCδ. However, while the LPS-induced suppression in cNOS activation shows reliance on the phosphorylation of PKCδ and PI3K on Ser, the effect of ghrelin is manifested by the increase in phosphorylation of PKCδ and PI3K on Tyr, as well as membrane translocation and phosphorylation of Akt on Ser⁴⁹³. Thus, our findings suggest that the LPS-induced suppression in cNOS activation is mediated by PKCδ-controlled phosphorylation of PI3K on Ser that interferes with the membrane recruitment of Akt and promotes cNOS phosphorylation on Thr⁴⁹⁷, and that ghrelin-elicited up-regulation in cNOS activation relies on the PKCδ-directed phosphorylation of PI3K on Tyr that stimulates the membrane localization of Akt and enhances cNOS phosphorylation on Ser¹¹⁷⁹.

Gastric Mucosa, H. pylori, Ghrelin, PKCδ, PI3K, cNOS Phosphorylation

Slomiany, B. and Slomiany, A. (2014) Protein Kinase Cδ-Mediated Posttranslational Phosphorylation of Constitutive Nitric Oxide Synthase Regulates Gastric Mucosal Inflammatory Responses to Helicobacter pylori: Effect of Ghrelin. Journal of Biosciences and Medicines, 2, 20-33. doi: 10.4236/jbm.2014.25003.