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感染 Theileria annulata 的克隆细胞系中 NF-κB 激活的调节与寄生虫依赖性 IKK 信号体的检测和肌动蛋白细胞骨架的破坏有关。

Modulation of NF-kappaB activation in Theileria annulata-infected cloned cell lines is associated with detection of parasite-dependent IKK signalosomes and disruption of the actin cytoskeleton.

机构信息

Division of Molecular Pathobiology, Department of Clinical Research and VPH, Vetsuisse Faculty Bern, Bern, Switzerland.

出版信息

Cell Microbiol. 2010 Feb;12(2):158-73. doi: 10.1111/j.1462-5822.2009.01386.x. Epub 2009 Oct 5.

Abstract

Apicomplexan parasites within the genus Theileria have the ability to induce continuous proliferation and prevent apoptosis of the infected bovine leukocyte. Protection against apoptosis involves constitutive activation of the bovine transcription factor NF-kappaB in a parasite-dependent manner. Activation of NF-kappaB is thought to involve recruitment of IKK signalosomes at the surface of the macroschizont stage of the parasite, and it has been postulated that additional host proteins with adaptor or scaffolding function may be involved in signalosome formation. In this study two clonal cell lines were identified that show marked differences in the level of activated NF-kappaB. Further characterization of these lines demonstrated that elevated levels of activated NF-kappaB correlated with increased resistance to cell death and detection of parasite-associated IKK signalosomes, supporting results of our previous studies. Evidence was also provided for the existence of host- and parasite-dependent NF-kappaB activation pathways that are influenced by the architecture of the actin cytoskeleton. Despite this influence, it appears that the primary event required for formation of the parasite-dependent IKK signalosome is likely to be an interaction between a signalosome component and a parasite-encoded surface ligand.

摘要

锥虫属的边缘体寄生虫具有诱导受感染牛白细胞持续增殖和防止细胞凋亡的能力。抗细胞凋亡涉及以寄生虫依赖的方式使牛转录因子 NF-κB 持续激活。NF-κB 的激活被认为涉及在寄生虫的大滋养体阶段表面募集 IKK 信号小体,并且已经假设其他具有衔接或支架功能的宿主蛋白可能参与信号小体的形成。在这项研究中,鉴定出两种克隆细胞系,它们在激活的 NF-κB 水平上表现出明显的差异。对这些系的进一步表征表明,高水平的激活 NF-κB 与对细胞死亡的抵抗力增加和寄生虫相关的 IKK 信号小体的检测相关,支持了我们之前研究的结果。还提供了宿主和寄生虫依赖的 NF-κB 激活途径的证据,这些途径受肌动蛋白细胞骨架的结构影响。尽管存在这种影响,但对于寄生虫依赖的 IKK 信号小体的形成所需的主要事件似乎很可能是信号小体成分与寄生虫编码的表面配体之间的相互作用。

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