Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules
Cigarette smoke metal-catalyzed protein oxidation leads to vascular endothelial cell contraction by depolymerization of microtubules
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DOI：
10.1096/fj.04-3192com
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发表时间：
2005-07-01
期刊：
影响因子：
4.8
通讯作者：
Wick, G
中科院分区：
文献类型：
--
作者：
Bernhard, D;Csordas, A;Wick, G
吸烟是动脉粥样硬化发展的一个重要危险因素。然而，吸烟介导的血管壁损伤的病理生理学尚不清楚。利用从分析化学到细胞生物学的工具，我们发现香烟烟雾中含有金属，这些金属可以催化烟雾氧化剂对细胞蛋白质的直接氧化。细胞蛋白质的氧化导致微管功能的丧失，最终导致微管解聚和α-微管蛋白的蛋白酶体依赖性降解。由于微管塌陷，细胞骨架结构以及中间丝断裂，最终导致血管内皮细胞收缩。我们观察到烟雾提取物诱导的，钙蛋白酶依赖性降解的细胞内形式的血小板-内皮细胞粘附分子1/CD 31，以及释放的P-选择素/CD 62 P，IL-6和IL-8从内皮细胞进入上清液。众所周知，可溶性CD 62 β和IL-6水平的增加与人类吸烟有关。血管内皮细胞通透性的增加是动脉粥样硬化形成中的关键事件。这项工作突出了香烟烟雾诱导血管内皮细胞渗漏的化合物和机制。
Smoking is a significant risk factor for development of atherosclerosis. However, the pathophysiology of smoking-mediated vessel wall damage is not understood. With tools ranging from analytical chemistry to cell biology, we show that cigarette smoke contains metals that catalyze the direct oxidation of cellular proteins by smoke oxidants. Oxidation of cellular proteins causes a loss of microtubule function, culminating in microtubule depolymerization and proteasome-dependent degradation of alpha-tubulin. As a consequence of the microtubule collapse, cytoskeletal structures as well as intermediate filaments break down, leading finally to a contraction of vascular endothelial cells. We observed a smoke extract-induced, calpain-dependent degradation of the intracellular form of platelet-endothelial cell adhesion molecule 1/CD31, as well as a release of P-selectin/ CD62P, IL-6, and IL-8 from endothelial cells into the supernatant. Increased levels of soluble CD62P and IL-6 are well known to be associated with smoking in humans. Increased permeability of the vascular endothelium is a crucial event in atherogenesis. This work highlights the compounds and mechanisms by which cigarette smoke induces leakiness of the vascular endothelium.