Serine proteases increase oxidative stress in lung cells

Citation
K. Aoshiba et al., Serine proteases increase oxidative stress in lung cells, AM J P-LUNG, 281(3), 2001, pp. L556-L564
Citations number
37
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
ISSN journal
1040-0605 → ACNP
Volume
281
Issue
3
Year of publication
2001
Pages
L556 - L564
Database
ISI
SICI code
1040-0605(200109)281:3<L556:SPIOSI>2.0.ZU;2-U
Abstract
Several serine proteases are directly cytotoxic. We investigated whether th e cytotoxic effects of proteases are associated with increased levels of re active oxygen species (ROS) in cells. We found that treatment of lung fibro blasts or bronchial epithelial cells with relatively high concentrations (0 .1-100 U/ml) of neutrophil elastase, trypsin, and Pronase increased ROS lev els 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 bec ause the proteases also caused an increase in ROS in suspended cells, which precluded attachment to the extracellular matrix. The protease-induced inc rease in ROS appears to contribute to cytotoxicity because cell death induc ed by proteases was attenuated by treatment with catalase, a decomposer of H2O2, and accelerated by treatment with aminotriazole, a catalase inhibitor . These results suggest that several proteases increase oxidative stress, i ndicating a direct interaction between proteases and ROS in mediating cytot oxicity.