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首页> 外文期刊>Journal of immunology research. >The 19 kDa Mycobacterium tuberculosis Lipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor
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The 19 kDa Mycobacterium tuberculosis Lipoprotein (LpqH) Induces Macrophage Apoptosis through Extrinsic and Intrinsic Pathways: A Role for the Mitochondrial Apoptosis-Inducing Factor

机译:19 kDa结核分枝杆菌脂蛋白(LpqH)通过外在和内在途径诱导巨噬细胞凋亡:线粒体细胞凋亡诱导因子的作用。

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We describe the association of caspase-dependent and caspase-independent mechanisms in macrophage apoptosis induced by LpqH, a 19 kDa Mycobacterium tuberculosis lipoprotein. LpqH triggered TLR2 activation, with upregulation of death receptors and ligands, which was followed by a death receptor signaling cascade with activation of initiator caspase 8 and executioner caspase 3. In this caspase-mediated phase, mitochondrial factors were involved in loss of mitochondrial transmembrane potential (), release of cytochrome c, and caspase 9 activation. Interestingly, a caspase-independent pathway was also identified; by immunoblot, the mitochondrial apoptosis inducing factor (AIF) was demonstrated in nuclei and cytosol of LpqH-treated macrophages. Confocal microscopy revealed translocation of AIF to the nuclei of the majority of apoptotic cells. These findings emphasize the complex and redundant nature of the macrophage death response to mycobacteria.
机译:我们描述了由LpqH,一种19 kDa结核分枝杆菌脂蛋白诱导的巨噬细胞凋亡中的胱天蛋白酶依赖性和胱天蛋白酶非依赖性机制的关联。 LpqH触发TLR2激活,伴随死亡受体和配体的上调,随后是死亡受体信号级联反应,其中激活了启动子caspase 8和execution子手caspase3。在此caspase介导的阶段,线粒体因子参与了线粒体跨膜电位的丧失。 (),释放细胞色素c和激活caspase 9。有趣的是,还发现了一种不依赖caspase的途径。通过免疫印迹,在LpqH处理的巨噬细胞的细胞核和细胞核中证实了线粒体凋亡诱导因子(AIF)。共聚焦显微镜显示AIF易位至大多数凋亡细胞的细胞核。这些发现强调了巨噬细胞对分枝杆菌死亡反应的复杂和冗余性质。

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