Ghrelin Protects against the Detrimental Consequences of Porphyromonas gingivalis-Induced Akt Inactivation through S-Nitrosylation on Salivary Mucin Synthesis

Abstract EN

Disturbances in nitric oxide synthase isozyme system and the impairment in salivary mucin synthesis are well-recognized features associated with oral mucosal inflammatory responses to periodontopathic bacterium, P.

gingivalis.

In this study, using rat sublingual gland acinar cells, we report that P.

gingivalis LPS-induced impairment in mucin synthesis and associated suppression in Akt kinase activity were accompanied by a decrease in constitutive nitric oxide synthase (cNOS) activity and an induction in inducible nitric oxide synthase (iNOS) expression.

The LPS effect on Akt inactivation was manifested in the kinase S-nitrosylation and a decrease in its phosphorylation at Ser473.

Further, we demonstrate that a peptide hormone, ghrelin, countered the LPS-induced impairment in mucin synthesis.

This effect of ghrelin was reflected in the suppression of iNOS and the increase in Akt activation, associated with the loss in S-nitrosylation and the increase in phosphorylation, as well as cNOS activation through phosphorylation.

Our findings suggest that induction in iNOS expression by P.

gingivalis-LPS leads to Akt kinase inactivation through S-nitrosylation that detrimentally impacts cNOS activation through phosphorylation as well as mucin synthesis.

We also show that the countering effect of ghrelin on P.

gingivalis-induced impairment in mucin synthesis is associated with Akt activation through phosphorylation.