Streptococcus mutans GS-5 antigen I/II stimulates cell survival in serum deprived-cultures through PI3K/Akt pathways.
The antigen I/II (AgI/II) protein is a major surface protein that mediates the attachment of Streptococcus mutans (S. mutans) to the saliva-coated pellicle. Numerous studies have investigated not only the mechanisms by which AgI/II signaling is transduced within cells, but have also attempted to use AgI/II-specific antibodies to treat dental caries and host immune responses. However, little information is available about the effects of AgI/II on basic cellular events in bone cells. In this study, we examined the effects of the His-tagged recombinant N-terminal half of the AgI/II protein (rAgI/II-N) generated from S. mutans GS-5 on the viability, proliferation, and cell cycle progression of primary calvarial osteoblasts. We also investigated the mechanisms involved in the rAgI/II-N-mediated survival of serum-starved osteoblasts. We found that rAgI/II treatment attenuated the serum deprivation-induced decrease in cell viability and proliferation of osteoblasts. rAgI/II-N also prevented the loss of mitochondrial membrane potential (MMP), alterations in levels of two key mitochondrial Bcl-2 family proteins, and the accumulation of numerous cells into the sub-G(1) phase that were observed in serum-starved osteoblasts. Pharmacological inhibitors of phosphoinositide 3-kinase (PI3K), but not of extracellular signal-regulated kinase or Ras, blocked the rAgI/II-N-mediated protection against serum deprivation-induced cell death. Additional experiments revealed that the integrin α5β1-mediated PI3K pathway is required for rAgI/II-N-mediated Akt phosphorylation in osteoblasts. Collectively, these results suggest that rAgI/II-N induces survival signals in serum-starved osteoblasts through integrin-induced PI3K/Akt signaling pathways.
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0001, USA.
Young-Ok
YO
Son
Young-Mi
YM
Jeon
Yu-Shin
YS
Kim
Soon-Sun
SS
Park
Seung-Moon
SM
Park
Ji-Hae
JH
Kim
Jeong-Chae
JC
Lee
D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000502:physiology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D002453:Cell Cycle; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D054884:Host-Pathogen Interactions / Q000276:immunology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D010006:Osteoblasts / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D015398:Signal Transduction; D013295:Streptococcus mutans / Q000276:immunology* / Q000472:pathogenicity; D013312:Stress, Physiological
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016895:Culture Media, Serum-Free; D011994:Recombinant Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt