Porphyromonas gingivalisinfection sequesters pro-apoptotic Bad through Akt in primary gingival epithelial cells
- 11 March 2010
- journal article
- Published by Wiley in Molecular Oral Microbiology
- Vol. 25 (2), 89-101
- https://doi.org/10.1111/j.2041-1014.2010.00569.x
Abstract
Porphyromonas gingivalis, a self‐limiting oral pathogen, can colonize and replicate in gingival epithelial cells (GECs). P. gingivalis‐infected GECs are protected from mitochondrion‐dependent apoptosis, partially through activation of phosphatidyl inositol 3‐kinase/Akt signaling. Biochemical events associated with P. gingivalis‐induced inhibition of apoptosis include the blocking of mitochondrial membrane permeability and cytochrome‐c release. We studied functional importance of Akt and the status of associated key mitochondrial molecules, pro‐apoptotic Bad and caspase‐9, during infection of GECs. We found that P. gingivalis infection caused significant phosphorylation of Bad progressively, while messenger RNA levels for Bad slowly decreased. Fluorescence microscopy showed translocation of the mitochondrial Bad to the cytosol post‐infection. Conversely, P. gingivalis lost the ability to promote phosphorylation and translocation of Bad in Akt‐deficient GECs. Caspase‐9 activation induced by a chemical inducer of apoptosis was significantly inhibited by infection over time. However, Akt depletion by small interfering RNA did not reverse inhibition of caspase‐9 activation by infection. Hence, P. gingivalis inactivates pro‐apoptotic Bad through Akt. The inhibition of caspase‐9 activation appears to be independent of Akt. Overall, our findings suggest that Akt is a key component of anti‐apoptotic pathways stimulated by P. gingivalis. The P. gingivalis uses other mitochondrial pathways to protect host cells from cell‐death and to ensure its survival in gingival epithelium.Keywords
This publication has 36 references indexed in Scilit:
- The chronicles of Porphyromonas gingivalis: the microbium, the human oral epithelium and their interplayMicrobiology, 2008
- P. gingivalis accelerates gingival epithelial cell progression through the cell cycleMicrobes and Infection, 2008
- ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X7-mediated host-cell apoptosisCellular Microbiology, 2007
- Quantitative proteomics of intracellular Porphyromonas gingivalisProteomics, 2007
- Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalisCellular Microbiology, 2007
- Recruitment of BAD by the Chlamydia trachomatis Vacuole Correlates with Host-Cell SurvivalPLoS Pathogens, 2006
- Apoptosis in infectious disease: how bacteria interfere with the apoptotic apparatusMedical Microbiology and Immunology, 2005
- BAD Is a Pro-survival Factor Prior to Activation of Its Pro-apoptotic FunctionOnline Journal of Public Health Informatics, 2004
- BCL-2 FAMILY: Regulators of Cell DeathAnnual Review of Immunology, 1998
- Caspases: killer proteasesTrends in Biochemical Sciences, 1997