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Original Article
Production of reactive persulfide species in chronic obstructive pulmonary disease
  1. Tadahisa Numakura1,
  2. Hisatoshi Sugiura1,
  3. Takaaki Akaike2,
  4. Tomoaki Ida2,
  5. Shigemoto Fujii2,
  6. Akira Koarai1,
  7. Mitsuhiro Yamada1,
  8. Katsuhiro Onodera1,
  9. Yuichiro Hashimoto1,
  10. Rie Tanaka1,
  11. Kei Sato1,
  12. Yutaka Shishikura1,
  13. Taizou Hirano1,
  14. Satoru Yanagisawa1,
  15. Naoya Fujino1,
  16. Tatsuma Okazaki1,
  17. Tsutomu Tamada1,
  18. Yasushi Hoshikawa3,
  19. Yoshinori Okada4,
  20. Masakazu Ichinose1
  1. 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan
  2. 2Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine, Sendai, Japan
  3. 3Department of Thoracic Surgery, Fujita Health University School of Medicine, Toyoake, Japan
  4. 4Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan
  1. Correspondence to Dr Hisatoshi Sugiura, Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Seiryou-machi, Aoba-ku, Sendai 980-8574, Japan; sugiura{at}rm.med.tohoku.ac.jp

Abstract

Background Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine β-synthase and cystathionine γ-lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown.

Objectives The aim of this study was to examine the production 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 patients with mild to moderate COPD.

Methods Lung tissues, primary lung cells, ELF and sputum were obtained. 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. The amounts of synthases in the lung tissues, sputum and primary cells were quantified.

Results The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from patients with COPD. The amounts of reactive persulfides and polysulfides in the lung cells had a positive correlation with the degree of airflow limitation. By contrast, the amounts of the synthases were increased in the lung tissues and sputum cells of patients with COPD.

Conclusions We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.

  • Oxidative Stress

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Footnotes

  • Contributors TN: cell culture, biochemical studies, immunohistochemical analysis, interpretation of results. HS: design of the study, technical advice, interpretation of results, writing of the manuscript. TA: design of the study, technical advice, measurement of reactive persulfides, interpretation of results. TI: measurement of reactive persulfides, technical advice, interpretation of results. SF: technical advice, measurement of reactive persulfides, interpretation of results. AK: technical advice, interpretation of results, recruitment of patients. MY: technical advice, interpretation of results, recruitment of patients. KO: recruitment of patients, informed consent of patients, technical advice. YH: cell culture, biochemical studies, technical advice, interpretation of results. RT: recruitment of patients, informed consent of patients.KS: recruitment of patients, informed consent of patients. YS: cell culture, technical advice, interpretation of results. TH: biochemical studies, technical advice, interpretation of results. SY: recruitment of patients, technical advice, interpretation of results. NF: technical advice, interpretation of results. TO: recruitment of patients, informed consent of patients. TT: recruitment of patients, informed consent of patients. YH: recruitment of patients, informed consent of patients. YO: recruitment of patients, informed consent of patients.MI: design of the study, interpretation of results, writing of the manuscript.

  • Funding This study was supported by grants from the Japan Society for the Promotion of Science Grant (#26293195, #16K15453, #16H05307, #17H04180) and a grant from the Practical Research Project for Allergic Diseases and Immunology (Research on Allergic Diseases and Immunology) from the Japan Agency for Medical Research and Development, AMED.

  • Competing interests None declared.

  • Ethics approval Tohoku University Graduate School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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