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A2662 - Production of Reactive Persulfide Species and Their Effects in the Lungs of Patients with COPD
Author Block: T. Numakura1, H. Sugiura1, T. Akaike2, M. Yamada1, T. Ichikawa1, S. Yanagisawa1, A. Koarai1, M. Ichinose1; 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan, 2Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Rationale: Reactive persulfide and polysulfide species have recently been recognized as potent antioxidants. They are biosynthesized by cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE). Although oxidative stress is a major etiological factor driving chronic obstructive pulmonary disease (COPD), the production of reactive persulfide and polysulfide species and their effects in the lungs of patients with COPD remain unknown. The aims of this study were the following: 1) to examine the amounts of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lung-resident cells and epithelial lining fluid (ELF) obtained from mild to moderate COPD patients; 2) to investigate the effects of a persulfide donor on the oxidative stress-induced cellular injury and production of proinflammatory mediators.
Methods: Primary bronchial epithelial cells and lung fibroblasts were obtained from the lungs of healthy subjects and patients with COPD. ELF of the study subjects was collected by bronchoscopic microsampling technique. The amounts of reactive persulfides and polysulfides in the cells and ELF were measured by liquid chromatography-tandem mass spectrometry with β-(4-hydroxyphenyl) ethyl iodoacetamide as a trapping agent for hydroper/polysulfides. Cellular injury, the production of reactive oxygen species (ROS) and release of proinflammatory mediators, such as interleukin-8 and matrix metalloproteinases, from lung-resident cells were measured after treatment with hydrogen peroxide (H2O2) with or without a persulfide donor pretreatment.
Results: The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from the patients with COPD compared to those from healthy subjects. The amounts of reactive persulfides and polysulfides in the lung cells were positively correlated with the degree of airflow obstruction represented by %FEV1. Treatment with H2O2 significantly reduced the amounts of intracellular reactive persulfides (i.e., GSSH and CysSSH), whereas the amounts of glutathione and cysteine did not change. The persulfide donor significantly reduced the H2O2-induced cellular injury, the production of ROS and release of proinflammatory mediators.
Conclusions: We identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. A donor of persulfide species may have potential as a novel antioxidant and anti-inflammatory strategy in COPD.