Serine proteases increase oxidative stress in lung cells.
Serine proteases increase oxidative stress in lung cells.
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DOI：
10.1152/ajplung.2001.281.3.l556
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发表时间：
2001-09
期刊：
影响因子：
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通讯作者：
K. Aoshiba;Kimihiko Yasuda;S. Yasui;J. Tamaoki;A. Nagai
中科院分区：
文献类型：
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作者：
K. Aoshiba;Kimihiko Yasuda;S. Yasui;J. Tamaoki;A. Nagai
几种丝氨酸蛋白酶具有直接的细胞毒性。我们研究了蛋白水解酶的细胞毒性效应是否与细胞内活性氧自由基(ROS)水平的增加有关。我们发现，用相对较高浓度(0.1-100U/ml)的中性粒细胞弹性蛋白酶、胰蛋白酶和Pronase处理肺成纤维细胞或支气管上皮细胞会增加线粒体和细胞质中的ROS水平。由8-羟基-2‘-脱氧鸟苷和丙二醛+4-羟基烯醛的生成确定，蛋白酶诱导的ROS增加与细胞氧化损伤有关。蛋白水解酶诱导的ROS增加不仅仅是由于细胞脱离，因为该酶还导致悬浮细胞中ROS的增加，从而排除了与细胞外基质的附着。蛋白水解酶诱导的ROS增加可能与细胞毒性有关，因为H(2)O(2)的分解者过氧化氢酶可减轻蛋白水解酶诱导的细胞死亡，而过氧化氢酶抑制剂氨基三氮唑可促进细胞死亡。这些结果表明，几种蛋白酶增加了氧化应激，表明在介导细胞毒性的过程中，蛋白酶和ROS之间存在直接的相互作用。
Several serine proteases are directly cytotoxic. We investigated whether the cytotoxic effects of proteases are associated with increased levels of reactive oxygen species (ROS) in cells. We found that treatment of lung fibroblasts or bronchial epithelial cells with relatively high concentrations (0.1--100 U/ml) of neutrophil elastase, trypsin, and Pronase increased ROS levels in the mitochondria and cytoplasm. The protease-induced increase in ROS was associated with oxidative cellular injury as determined by generation of 8-hydroxy-2'-deoxyguanosine and malonaldehyde plus 4-hydroxyalkenal. The protease-induced increase in ROS was not merely due to cell detachment because the proteases also caused an increase in ROS in suspended cells, which precluded attachment to the extracellular matrix. The protease-induced increase in ROS appears to contribute to cytotoxicity because cell death induced by proteases was attenuated by treatment with catalase, a decomposer of H(2)O(2), and accelerated by treatment with aminotriazole, a catalase inhibitor. These results suggest that several proteases increase oxidative stress, indicating a direct interaction between proteases and ROS in mediating cytotoxicity.