2007 Fiscal Year Final Research Report Summary
Molecular biological analysis of sensitivity and individual differences in cardiovascular diseases induced by periodontopathic bacteria
| Project/Area Number |
18390562
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Periodontal dentistry
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| Research Institution | Kyushu Dental College |
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Principal Investigator |
NISHIHARA Tatsuji Kyushu Dental College, Dentistry, Professor (80192251)
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| Co-Investigator(Kenkyū-buntansha) |
AKIFUSA Sumio Kyushu University, Dentistry, Assistant Professor (2007) (40295861)
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| Project Period (FY) |
2006 – 2007
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| Keywords | periodontal diseases / periodontopathic bacteria / chronic diseases / atherogenesis / endothelial cells / macrophages / arterial sclerosis / hvoerlioemia |
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| Research Abstract |
The periodontopathic bacterium Actinobacillus actinomycetemcomitans has been implicated in the pathogenesis of periodontal diseases. We previously reported that infection with the organism induced apoptosis in the mouse macrophage cell line J774.1. In the present study, we examined the role of caspases during apoptosis in A. actionomycetemcomitans-infected J774.1 cells. A large number of apoptotic cells were detected by flow cytometric analysis in infected J774.1 cells, while the inhibitors of caspases-9, -6 and -3/7 completely blocked the induction of apoptosis. The expression of the cleaved forms of caspase-6 and -7 were detected during apoptosis in infected J774.1 cells. Immunoblot analysis revealed that the caspase-9 inhibitor blocked the expression of the cleaved forms of caspase-6 and -7, while the caspase-3 inhibitor blocked the expression of the cleaved form of caspase-7, but not caspase-6. It is known that lamin A/C and poly (ADP-ribose)polymerase (PARP) are essential nuclear components for maintaining normal cell functions and viability, and both were cleaved in the infected J774.1 cells. Immunoblot analysis also revealed that the caspase-6 inhibitor blocked the cleavage of lamin A/C, while caspase-3/7 inhibitors blocked the cleavage of PARP. Taken together, our results suggest that the activation of caspases and subsequent cleavage of lamin A/C and PARP are involved in morphological changes of apoptotic macrophages infected with A. actinomycetemcomitans. Further, our results indicate that the activated effector caspases, caspase-6 and -7 played a critical role in the degradation of lamin A/C and PARP in apoptotic macrophages infected with A. actinomycetemcomitans. Our results also demonstrated that application of caspase inhibitors may suppress the induction of apoptosis in macrophages infected with periodontopathic bacteria.
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