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Fibroblast apoptosis induced by Porphyromonas gingivalis is stimulated by a gingipain and caspase-independent pathway that involves apoptosis-inducing factor.
Fibroblast apoptosis induced by Porphyromonas gingivalis is stimulated by a gingipain and caspase-independent pathway that involves apoptosis-inducing factor.
- Source :
-
Cellular microbiology [Cell Microbiol] 2007 Nov; Vol. 9 (11), pp. 2667-75. Date of Electronic Publication: 2007 Jun 24. - Publication Year :
- 2007
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Abstract
- Porphyromonas gingivalis is an oral bacterium that causes pathology in a number of dental infections that are associated with increased fibroblast cell death. Studies presented here demonstrated that P. gingivalis stimulates cell death by apoptosis rather than necrosis. Unlike previous studies apoptosis was induced independent of proteolytic activity and was also independent of caspase activity because a pancaspase inhibitor, Z-VAD-fmk, had little effect. Moreover, P. gingivalis downregulated caspase-3 mRNA levels and caspase-3 activity. The consequence of this downregulation was a significant reduction in tumour necrosis factor-alpha-induced apoptosis, which is caspase-3-dependent. Immunofluorescence and immunoblot analysis revealed P. gingivalis-induced translocation of apoptosis-inducing factor (AIF) from the cytoplasm to the nucleus. siRNA studies were undertaken and demonstrated that P. gingivalis stimulated cell death was significantly reduced when AIF was silenced (P < 0.05). Treatment of human gingival fibroblasts with H-89, a protein kinase A inhibitor that blocks AIF activation also reduced P. gingivalis-induced apoptosis (P < 0.05). These results indicate that P. gingivalis causes fibroblast apoptosis through a pathway that involves protein kinase A and AIF, is not dependent upon bacterial proteolytic activity and is also independent of the classic apoptotic pathways involving caspase-3.
- Subjects :
- Adhesins, Bacterial genetics
Adhesins, Bacterial metabolism
Amino Acid Chloromethyl Ketones pharmacology
Apoptosis drug effects
Apoptosis Inducing Factor genetics
Apoptosis Inducing Factor physiology
Caspase 2 genetics
Caspase 2 metabolism
Caspase 3 genetics
Caspase 3 metabolism
Caspases genetics
Caspases metabolism
Cysteine Endopeptidases genetics
Cysteine Endopeptidases metabolism
Enzyme-Linked Immunosorbent Assay
Fibroblasts cytology
Fibroblasts microbiology
Fluorescent Antibody Technique
Gingipain Cysteine Endopeptidases
Humans
Immunoblotting
In Situ Nick-End Labeling
Isoquinolines pharmacology
Porphyromonas gingivalis genetics
Porphyromonas gingivalis metabolism
RNA, Small Interfering genetics
Signal Transduction drug effects
Sulfonamides pharmacology
Tumor Necrosis Factor-alpha pharmacology
Apoptosis physiology
Apoptosis Inducing Factor metabolism
Fibroblasts metabolism
Porphyromonas gingivalis growth & development
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1462-5814
- Volume :
- 9
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cellular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 17587332
- Full Text :
- https://doi.org/10.1111/j.1462-5822.2007.00987.x