Serine proteases increase oxidative stress in lung cells

• Published in: American journal of physiology. Lung cellular and molecular physiology 2001-09, Vol.281 (3), p.556-L564
• Main Authors: Aoshiba, Kazutetsu, Yasuda, Kimihiko, Yasui, Shuji, Tamaoki, Jun, Nagai, Atsushi
• Format: Article
• Language: English
• Subjects: Bronchi - cytology; Bronchi - metabolism; Bronchi - physiology; Cell Survival - drug effects; Cells, Cultured; Epithelial Cells - metabolism; Epithelial Cells - physiology; Fibroblasts - metabolism; Fibroblasts - physiology; Humans; Intracellular Membranes - metabolism; Leukocyte Elastase - pharmacology; Lung - cytology; Lung - metabolism; Lung - physiology; Mitochondria - metabolism; Oxidative Stress - physiology; Pronase - pharmacology; Reactive Oxygen Species - metabolism; Serine Endopeptidases - pharmacology; Serine Endopeptidases - physiology; Trypsin - pharmacology
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.281.3.l556

First Department of Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-8666, Japan 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. oxidants; reactive oxygen species; elastase; trypsin; Pronase