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.
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Authors | Young-Ok Son, Young-Mi Jeon, Yu-Shin Kim, Soon-Sun Park, Seung-Moon Park, Ji-Hae Kim, Jeong-Chae Lee |
Journal | Journal of cellular biochemistry
(J Cell Biochem)
Vol. 113
Issue 5
Pg. 1724-32
(May 2012)
ISSN: 1097-4644 [Electronic] United States |
PMID | 22213029
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Wiley Periodicals, Inc. |
Chemical References |
- Antigens, Bacterial
- Bacterial Proteins
- Culture Media, Serum-Free
- Recombinant Proteins
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
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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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