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Molecular biological analysis of sensitivity and individual differences in cardiovascular diseases induced by periodontopathic bacteria

牙周病菌所致心血管疾病敏感性及个体差异的分子生物学分析

基本信息

批准号：
18390562
负责人：
NISHIHARA Tatsuji
金额：
$ 10.19万
依托单位：
Kyushu Dental College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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.

牙周致病菌伴放线放线杆菌与牙周病的发病机制有关。我们以前报道，感染的有机体诱导小鼠巨噬细胞系J774.1的凋亡。在本研究中，我们研究了半胱天冬酶在A.共放线菌感染的J774.1细胞。流式细胞仪检测到大量凋亡细胞，而caspase-9、-6和-3/7抑制剂完全阻断了凋亡诱导。在感染的J774.1细胞凋亡过程中检测到切割形式的caspase-6和-7的表达。免疫印迹分析显示，半胱天冬酶-9抑制剂阻断了半胱天冬酶-6和-7的裂解形式的表达，而半胱天冬酶-3抑制剂阻断了半胱天冬酶-7的裂解形式的表达，但不阻断半胱天冬酶-6。已知核纤层蛋白A/C和聚（ADP-核糖）聚合酶（PARP）是维持正常细胞功能和活力的必需核组分，并且两者在感染的J774.1细胞中被切割。免疫印迹分析还显示，半胱天冬酶-6抑制剂阻断核纤层蛋白A/C的切割，而半胱天冬酶-3/7抑制剂阻断PARP的切割。综上所述，我们的结果表明，半胱天冬酶的激活和随后的核纤层蛋白A/C和PARP的切割参与了A.伴放线菌此外，我们的研究结果表明，激活的效应caspase-6和-7在A.伴放线菌我们的研究结果还表明，应用半胱天冬酶抑制剂可以抑制牙周病细菌感染的巨噬细胞凋亡的诱导。