Nitric oxide interferes with salivary mucin synthesis: Involvement of ERK and p38 mitogen-activated protein kinase

Background: Nitric oxide (NO), a pluripotent molecule, is an important biological messenger that plays a role in the regulation of tissue homeostasis and pathophysiological processes. Methods: Using sublingual salivary gland acinar cells in culture, we investigated the effect of NO on mucus glycoprotein synthesis, apoptotic processes, and the involvement of extracellular signal-regulated kinase (ERK) and p38 mitogen activated protein kinase (MAPK). Results: Exposure of the acinar cells to NO donor led to a dose-dependent decrease (up to 42.8%) in mucus glycoprotein synthesis, and this effect of NO was accompanied by a marked increase in caspase-3 activity and apoptosis. Inhibition of ERK with PD98059 accelerated (up to 35.4%) the NO-induced decrease in the glycoprotein synthesis, and cause further enhancement in caspase-3 (up to 27.2%) activity and apoptosis (64.9%). On the other hand, blockade of p38 kinase with SB203580 produced a dose-dependent reversal (up to 42%) in the NO-induced reduction in the glycoprotein synthesis, and substantially countered the NO-induced increases in caspase-3 activity (by 62.8%) and apoptosis (by 57.6%). Moreover, caspase-3 inhibitor, Ac-DEVD-CHO, not only blocked the NO-induced increase in caspase-3 activity but also produced an increase in the glycoprotein synthesis. Conclusions: Together, our data indicate that the modulatory influence of NO on salivary mucin synthesis is closely linked to ERK and p38 protein kinase activation, in conjunction with caspase-3 activation and apoptosis.