Role of mitogen-activated protein kinase kinase in Porphyromonas gingivalis-induced myocardial cell hypertrophy and apoptosis.

Secreted factors present in the medium following growth of the periodontal pathogen Porphyromonas gingivalis cause increased cardiomyocyte hypertrophy and apoptosis, whereas secreted factors from Actinobacillus actinomycetemcomitans and Prevotella intermedia have no such effects. The purpose of this study was to clarify the role of mitogen-activated protein kinase (MAPK)/extracellular-regulated protein kinase (ERK) pathways in P. gingivalis medium-induced H9c2 myocardial cell hypertrophy and apoptosis. Cellular morphology, DNA fragmentation, nuclear condensation, total mitogen-activated protein kinase/extracellular-regulated protein kinase-1 (ERK-1), total ERK-1 protein, and phosphorylated ERK-1 protein products in cultured H9c2 myocardial cells were measured by actin immunofluorescence, agarose gel electrophoresis, nuclear condensation, and western blotting following stimulation with P. gingivalis spent growth medium or pre-administration of U0126, a potent MEK-1/2 inhibitor. Components of P. gingivalis spent culture medium not only resulted in increased total MEK-1 and ERK-1 protein products, but also caused increased cellular size, DNA fragmentation, and nuclear condensation in H9c2 cells. These three parameters, and the phosphorylated ERK-1 protein products of H9c2 cells treated with P. gingivalis medium, were all significantly reduced after pre-administration of U0126. The results suggest that P. gingivalis-secreted factors may initiate MEK/ERK signal pathways and lead to myocardial cell hypertrophy and apoptosis.