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Serine proteases increase oxidative stress in lung cells
1First Department of Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-8666, Japan. kaoshiba@chi.twmu.ac.jp
Summary
Several proteases increase reactive oxygen species (ROS) levels, causing oxidative cellular injury and cell death. This suggests a direct link between protease activity and oxidative stress in cytotoxicity.
Area of Science:
- Cell Biology
- Biochemistry
- Toxicology
Background:
- Serine proteases are known to induce direct cytotoxicity.
- The underlying mechanisms, particularly the role of oxidative stress, require further investigation.
Purpose of the Study:
- To investigate the association between protease activity and reactive oxygen species (ROS) generation.
- To determine if ROS contribute to protease-induced cytotoxicity.
Main Methods:
- Treatment of lung fibroblasts and bronchial epithelial cells with neutrophil elastase, trypsin, and Pronase.
- Measurement of ROS levels in mitochondria and cytoplasm.
- Assessment of oxidative cellular injury markers (8-hydroxy-2'-deoxyguanosine, malonaldehyde, 4-hydroxyalkenal).
- Evaluation of protease effects on suspended cells to rule out detachment artifacts.
- Analysis of cell death modulation by catalase and aminotriazole.
Main Results:
- Protease treatment significantly increased ROS levels in both mitochondrial and cytoplasmic compartments.
- Increased ROS correlated with markers of oxidative cellular injury.
- Protease-induced ROS increase occurred independently of cell attachment.
- Catalase treatment attenuated protease-induced cell death, while catalase inhibition accelerated it.
Conclusions:
- Several serine proteases elevate cellular ROS levels, contributing to oxidative stress.
- Protease-induced ROS play a direct role in mediating cytotoxicity.
- This highlights a significant interaction between proteases and ROS in cellular damage.