Role of constitutive nitric oxide synthase S-nitrosylation in Helicobacter pylori-induced gastric mucosal cell apoptosis: effect of ghrelin.
Infection with H. pylori is a primary factor in the etiology of gastric disease, and the excessive NO generation and a massive rise in apoptosis are well recognized features that characterize the mucosal inflammatory responses to the bacterium and its lipopolysaccharide (LPS). Here, we report that H. pylori LPS-induced enhancement in gastric mucosal cell apoptosis and NO generation was associated with the suppression in constitutive nitric oxide synthase (cNOS) activity and a marked up-regulation in the activity of inducible nitric oxide synthase (iNOS). Further, we demonstrate that the detrimental effect of the LPS on cNOS was manifested in the enzyme protein S-nitrosylation, that was susceptible to suppression by iNOS inhibitor, 1400W. Moreover, we show that the countering effect of peptide hormone, ghrelin, on the LPS-induced changes in apoptosis and cNOS activity was reflected in the loss in cNOS S-nitrosylation and the increase in the enzyme phosphorylation. These findings demonstrate that the disturbances in gastric mucosal NO generation system caused by H. pylori result from the iNOS-derived NO suppression of cNOS activation through S-nitrosylation. We also report that ghrelin protection against H. pylori-induced gastric mucosal proapoptotic events involves cNOS activation manifested by the increase in enzyme protein phosphorylation and a decrease in its S-nitrosylation.
Slomiany
B L
BL
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA. slomiabr@umdnj.edu
Slomiany
A
A
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001596:Benzylamines / Q000494:pharmacology; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D054439:Ghrelin / Q000378:metabolism* / Q000494:pharmacology; D016480:Helicobacter pylori / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats
D000578:Amidines; D001596:Benzylamines; D054439:Ghrelin; D008070:Lipopolysaccharides; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II