Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments.
Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments.
复制标题
缺氧诱导的角蛋白中间丝降解需要线粒体活性氧。
DOI：
10.1096/fj.08-128967
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Ridge,KarenM
中科院分区：
文献类型：
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作者：
Na,Ni;Chandel,NavdeepS;Litvan,Juan;Ridge,KarenM
低氧会对上皮细胞骨架造成应激和结构改变。已知中间丝(IF)网络会对压力作出反应而重组。我们检测了暴露在低氧环境下的大鼠肺泡上皮II型(ATII)细胞角蛋白IF的表达是否改变。与正常大鼠分离的ATII细胞相比，低氧大鼠ATII细胞角蛋白水平显著降低。为了确定调控这一过程的机制，我们研究了暴露在1.5%氧气中的A549细胞(一种肺泡上皮细胞株)角蛋白IF网络的变化。我们观察到角蛋白8和18蛋白随时间的分解-降解，这与活性氧物种(ROS)的增加有关。缺氧处理的缺乏线粒体DNA的A549细胞或接受针对线粒体复合体III的Rieske铁硫蛋白的小干扰RNA处理的A549细胞，如果网络解体和降解，则没有增加ROS的水平，角蛋白也没有增加。超氧化物歧化酶(SOD)/过氧化氢酶类似物(EUK-134)可以阻止低氧介导的角蛋白IF的降解，就像SOD1的过表达一样，但不能阻止SOD2的过度表达。因此，我们提供的证据表明，缺氧通过线粒体复合体III产生的活性氧物种促进角蛋白IF网络的分解和降解。-Na，N，Chandel，N.S.，Litvan，J.，Ridge，K.M.线粒体活性氧物种是缺氧诱导的角蛋白中间丝降解所必需的。
Hypoxia can cause stress and structural changes to the epithelial cytoskeleton. The intermediate filament (IF) network is known to reorganize in response to stress. We examined whether rats exposed to hypoxia had altered keratin IF expression in their alveolar epithelial type II (ATII) cells. There was a significant decrease in keratin protein levels in hypoxic ATII cells compared with those in ATII cells isolated from normoxic rats. To define the mechanisms regulating this process we studied changes to the keratin IF network in A549 cells (an alveolar epithelial cell line) exposed to 1.5% oxygen. We observed a time-dependent disassembly-degradation of keratin 8 and 18 proteins, which was associated with an increase in reactive oxygen species (ROS). Hypoxia-treated A549 cells deficient in mitochondrial DNA or A549 cells treated with a small interfering RNA against the Rieske iron-sulfur protein of mitochondrial complex III did not have increased levels of ROS nor was the keratin IF network disassembled and degraded. The superoxide dismutase (SOD)/catalase mimetic (EUK-134) prevented the hypoxia-mediated keratin IF degradation as did the overexpression of SOD1 but not of SOD2. Accordingly, we provide evidence that hypoxia promotes the disassembly and degradation of the keratin IF network via mitochondrial complex III-generated reactive oxygen species.—Na, N., Chandel, N. S., Litvan, J., Ridge, K. M. Mitochondrial reactive oxygen species are required for hypoxia-induced degradation of keratin intermediate filaments.