TY - JOUR
T1 - Supersulphides provide airway protection in viral and chronic lung diseases
AU - Matsunaga, Tetsuro
AU - Sano, Hirohito
AU - Takita, Katsuya
AU - Morita, Masanobu
AU - Yamanaka, Shun
AU - Ichikawa, Tomohiro
AU - Numakura, Tadahisa
AU - Ida, Tomoaki
AU - Jung, Minkyung
AU - Ogata, Seiryo
AU - Yoon, Sunghyeon
AU - Fujino, Naoya
AU - Kyogoku, Yorihiko
AU - Sasaki, Yusaku
AU - Koarai, Akira
AU - Tamada, Tsutomu
AU - Toyama, Atsuhiko
AU - Nakabayashi, Takakazu
AU - Kageyama, Lisa
AU - Kyuwa, Shigeru
AU - Inaba, Kenji
AU - Watanabe, Satoshi
AU - Nagy, Péter
AU - Sawa, Tomohiro
AU - Oshiumi, Hiroyuki
AU - Ichinose, Masakazu
AU - Yamada, Mitsuhiro
AU - Sugiura, Hisatoshi
AU - Wei, Fan Yan
AU - Motohashi, Hozumi
AU - Akaike, Takaaki
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-40182-4
DO - 10.1038/s41467-023-40182-4
M3 - Article
C2 - 37491435
AN - SCOPUS:85165672062
SN - 2041-1723
VL - 14
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4476
ER -