Nature Communications (Jul 2023)
Supersulphides provide airway protection in viral and chronic lung diseases
- Tetsuro Matsunaga,
- Hirohito Sano,
- Katsuya Takita,
- Masanobu Morita,
- Shun Yamanaka,
- Tomohiro Ichikawa,
- Tadahisa Numakura,
- Tomoaki Ida,
- Minkyung Jung,
- Seiryo Ogata,
- Sunghyeon Yoon,
- Naoya Fujino,
- Yorihiko Kyogoku,
- Yusaku Sasaki,
- Akira Koarai,
- Tsutomu Tamada,
- Atsuhiko Toyama,
- Takakazu Nakabayashi,
- Lisa Kageyama,
- Shigeru Kyuwa,
- Kenji Inaba,
- Satoshi Watanabe,
- Péter Nagy,
- Tomohiro Sawa,
- Hiroyuki Oshiumi,
- Masakazu Ichinose,
- Mitsuhiro Yamada,
- Hisatoshi Sugiura,
- Fan-Yan Wei,
- Hozumi Motohashi,
- Takaaki Akaike
Affiliations
- Tetsuro Matsunaga
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- Hirohito Sano
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Katsuya Takita
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Masanobu Morita
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- Shun Yamanaka
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Tomohiro Ichikawa
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Tadahisa Numakura
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Tomoaki Ida
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- Minkyung Jung
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- Seiryo Ogata
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- Sunghyeon Yoon
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- Naoya Fujino
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Yorihiko Kyogoku
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Yusaku Sasaki
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Akira Koarai
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Tsutomu Tamada
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Atsuhiko Toyama
- Analytical and Measuring Instruments Division, Shimadzu Corporation
- Takakazu Nakabayashi
- Bio-Structural Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
- Lisa Kageyama
- Bio-Structural Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University
- Shigeru Kyuwa
- Laboratory of Biomedical Science, Department of Veterinary Medical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo
- Kenji Inaba
- Institute of Multidisciplinary Research for Advanced Materials, Tohoku University
- Satoshi Watanabe
- Institute of Multidisciplinary Research for Advanced Materials, Tohoku University
- Péter Nagy
- Department of Molecular Immunology and Toxicology, National Institute of Oncology
- Tomohiro Sawa
- Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University
- Hiroyuki Oshiumi
- Department of Immunology, Graduate School of Medical Sciences, Kumamoto University
- Masakazu Ichinose
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Mitsuhiro Yamada
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Hisatoshi Sugiura
- Department of Respiratory Medicine, Tohoku University Graduate School of Medicine
- Fan-Yan Wei
- Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer, Tohoku University
- Hozumi Motohashi
- Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University
- Takaaki Akaike
- Department of Environmental Medicine and Molecular Toxicology, Tohoku University Graduate School of Medicine
- DOI
- https://doi.org/10.1038/s41467-023-40182-4
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 25
Abstract
Abstract Supersulphides are inorganic and organic sulphides with sulphur catenation with diverse physiological functions. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulphide synthase (CPERS). Here, we identify protective functions of supersulphides in viral airway infections (influenza and COVID-19), in aged lungs and in chronic lung diseases, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF). We develop a method for breath supersulphur-omics and demonstrate that levels of exhaled supersulphides increase in people with COVID-19 infection and in a hamster model of SARS-CoV-2 infection. Lung damage and subsequent lethality that result from oxidative stress and inflammation in mouse models of COPD, IPF, and ageing were mitigated by endogenous supersulphides production by CARS2/CPERS or exogenous administration of the supersulphide donor glutathione trisulphide. We revealed a protective role of supersulphides in airways with various viral or chronic insults and demonstrated the potential of targeting supersulphides in lung disease.
