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Streptococcus mutans GS-5 antigen I/II stimulates cell survival in serum deprived-cultures through PI3K/Akt pathways.

Abstract
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.
AuthorsYoung-Ok Son, Young-Mi Jeon, Yu-Shin Kim, Soon-Sun Park, Seung-Moon Park, Ji-Hae Kim, Jeong-Chae Lee
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 113 Issue 5 Pg. 1724-32 (May 2012) ISSN: 1097-4644 [Electronic] United States
PMID22213029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Wiley Periodicals, Inc.
Chemical References
  • Antigens, Bacterial
  • Bacterial Proteins
  • Culture Media, Serum-Free
  • Recombinant Proteins
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
Topics
  • Animals
  • Antigens, Bacterial (administration & dosage, physiology)
  • Bacterial Proteins (administration & dosage, immunology)
  • Cell Cycle
  • Cell Proliferation
  • Cell Survival (immunology)
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Host-Pathogen Interactions (immunology)
  • Mice
  • Mitochondria (metabolism)
  • Models, Biological
  • Osteoblasts (immunology, metabolism, microbiology, pathology)
  • Phosphatidylinositol 3-Kinases (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Recombinant Proteins (administration & dosage, immunology)
  • Signal Transduction
  • Streptococcus mutans (immunology, pathogenicity)
  • Stress, Physiological

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