Dysregulation of the endothelial cellular response to oxidative stress in cancer
Dysregulation of the endothelial cellular response to oxidative stress in cancer
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DOI：
10.1002/mc.20218
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发表时间：
2006-06-01
影响因子：
4.6
通讯作者：
Huot, Jacques
中科院分区：
文献类型：
--
作者：
Houle, Francois;Huot, Jacques
分子和细胞穿过血管壁的运输由血管内皮细胞控制。因此，这些细胞在调节心血管和全身稳态以及调节炎症等病理生理过程中发挥着积极作用。内皮调节系统的功能障碍及其无法有效处理其物理化学环境的能力会导致内皮完整性的破坏。例如，选择性内皮细胞通透性屏障的改变是氧化应激介导的损伤序列中的早期事件，可能导致循环癌细胞的外渗。多项证据表明，内皮屏障的调节受到信号通路激活的严格调节，这些信号通路集中于肌动蛋白细胞骨架动力学的调节。特别是，内皮层响应氧化应激的完整性受到细胞外信号调节激酶 (ERK) 和应激激活蛋白激酶 2/p38 (SAPK2/p38) 途径的平衡激活的严格调节。 SAPK2/p38 途径的激活需要触发肌动蛋白聚合，而通过磷酸化原肌球蛋白-1 来激活 ERK 途径会触发粘着斑的形成，从而使 SAPK2/p38 生成的肌动蛋白丝锚定成束成应力纤维。通过抑制 ERK 来调节这种平衡会导致膜起泡，这是氧化毒性的早期表现，与内皮层完整性的破坏有关。 (c) 2006 Wiley-Liss, Inc.
The traffic of molecules and cells across the vessel wall is gated by vascular endothelial cells. in accordance, these cells play an active role in regulating cardiovascular and systemic homeostasis and in modulating physiopathological processes such as inflammation. Dysfunction of the regulatory systems of the endothelium and its incapacity to efficiently deal with its physicochemical surrounding leads to disruption of endothelial integrity. For example, alterations of the selective endothelial cell permeability barrier are early events in the sequence of oxidative stress-mediated injury that may contribute to extravasation of circulating cancer cells. Several lines of evidence indicate that the regulation of the endothelial barrier is tightly regulated by activation of signaling pathways that converge on the regulation of actin cytoskeletal dynamics. In particular, the integrity of the endothelial layer in response to oxidative stress is tightly regulated by the balanced activation of the extracellular-signal regulated kinase (ERK) and the stress-activated protein kinase-2/p38 (SAPK2/p38) pathways. Activation of the SAPK2/p38 pathway is required to trigger actin polymerization, whereas activation of the ERK pathway by contributing to phosphorylate tropomyosin-1 triggers the formation of focal adhesions allowing the anchorage of actin filaments generated by SAPK2/p38 to bundle into stress fibers. Dysregulation of this equilibrium by inhibiting ERK leads to membrane blebbing, an early manifestation of oxidative toxicity that is associated with disruption of the endothelial layer integrity. (c) 2006 Wiley-Liss, Inc.