Kustermans Gaelle, El Benna Jamel, Piette Jacques, Legrand-Poels Sylvie
Laboratory of Virology and Immunology, Institute of Pathology, University of Liège, B-4000 Liege, Belgium.
Biochem J. 2005 Apr 15;387(Pt 2):531-40. doi: 10.1042/BJ20041318.
Although several reports showed the effect of compounds disrupting microtubules on NF-kappaB (nuclear factor kappaB) activation, nothing is known about agents perturbing actin dynamics. In the present study, we have shown that actin cytoskeleton disruption induced by actin-depolymerizing agents such as cytochalasin D and latrunculin B and actin-polymerizing compounds such as jasplakinolide induced NF-kappaB activation in myelomonocytic cells. The transduction pathway involved the IkappaB (inhibitory kappaB) kinase complex and a degradation of IkappaBalpha. We have shown that NF-kappaB activation in response to the perturbation of actin dynamics required reactive oxygen species, as demonstrated by the effect of antioxidants. Actin cytoskeleton disruption by cytochalasin D induced O2- release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47phox. NF-kappaB activation after actin cytoskeleton disruption could be physiologically relevant during monocyte activation and/or recruitment into injured tissues, where cellular attachment, migration and phagocytosis result in cyclic shifts in cytoskeletal organization and disorganization.
尽管有几份报告显示破坏微管的化合物对核因子κB（NF-κB）激活有影响，但对于干扰肌动蛋白动力学的因子却一无所知。在本研究中，我们发现细胞松弛素D和拉春库林B等肌动蛋白解聚剂以及茉莉素内酯等肌动蛋白聚合化合物诱导的肌动蛋白细胞骨架破坏可在骨髓单核细胞中诱导NF-κB激活。转导途径涉及抑制性κB（IkappaB）激酶复合物以及IkappaBα的降解。我们已表明，如抗氧化剂的作用所示，对肌动蛋白动力学扰动的NF-κB激活需要活性氧。细胞松弛素D对肌动蛋白细胞骨架的破坏通过激活NADPH氧化酶诱导人单核细胞释放超氧阴离子，这通过p47phox的磷酸化和膜转位得以证实。肌动蛋白细胞骨架破坏后的NF-κB激活在单核细胞激活和/或募集到受损组织的过程中可能具有生理相关性，在这些组织中，细胞附着、迁移和吞噬作用会导致细胞骨架组织和紊乱的周期性变化。
