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 () and Takaaki Akaike ()
Additional contact information
Tetsuro Matsunaga: Tohoku University Graduate School of Medicine
Hirohito Sano: Tohoku University Graduate School of Medicine
Katsuya Takita: Tohoku University Graduate School of Medicine
Masanobu Morita: Tohoku University Graduate School of Medicine
Shun Yamanaka: Tohoku University Graduate School of Medicine
Tomohiro Ichikawa: Tohoku University Graduate School of Medicine
Tadahisa Numakura: Tohoku University Graduate School of Medicine
Tomoaki Ida: Tohoku University Graduate School of Medicine
Minkyung Jung: Tohoku University Graduate School of Medicine
Seiryo Ogata: Tohoku University Graduate School of Medicine
Sunghyeon Yoon: Tohoku University Graduate School of Medicine
Naoya Fujino: Tohoku University Graduate School of Medicine
Yorihiko Kyogoku: Tohoku University Graduate School of Medicine
Yusaku Sasaki: Tohoku University Graduate School of Medicine
Akira Koarai: Tohoku University Graduate School of Medicine
Tsutomu Tamada: Tohoku University Graduate School of Medicine
Atsuhiko Toyama: Shimadzu Corporation
Takakazu Nakabayashi: Tohoku University
Lisa Kageyama: Tohoku University
Shigeru Kyuwa: The University of Tokyo
Kenji Inaba: Tohoku University
Satoshi Watanabe: Tohoku University
Péter Nagy: National Institute of Oncology
Tomohiro Sawa: Kumamoto University
Hiroyuki Oshiumi: Kumamoto University
Masakazu Ichinose: Tohoku University Graduate School of Medicine
Mitsuhiro Yamada: Tohoku University Graduate School of Medicine
Hisatoshi Sugiura: Tohoku University Graduate School of Medicine
Fan-Yan Wei: Tohoku University
Hozumi Motohashi: Tohoku University
Takaaki Akaike: Tohoku University Graduate School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 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.

Date: 2023
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DOI: 10.1038/s41467-023-40182-4

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