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Supersulfide catalysis for nitric oxide and aldehyde metabolism

Abundant formation of endogenous supersulfides, which include reactive persulfide species and sulfur catenated residues in thiols and proteins (supersulfidation), has been observed. We found here that supersulfides catalyze S-nitrosoglutathione (GSNO) metabolism via glutathione-dependent electron tr...

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Autores principales: Kasamatsu, Shingo, Nishimura, Akira, Alam, Md. Morshedul, Morita, Masanobu, Shimoda, Kakeru, Matsunaga, Tetsuro, Jung, Minkyung, Ogata, Seiryo, Barayeu, Uladzimir, Ida, Tomoaki, Nishida, Motohiro, Nishimura, Akiyuki, Motohashi, Hozumi, Akaike, Takaaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10438454/
https://www.ncbi.nlm.nih.gov/pubmed/37595031
http://dx.doi.org/10.1126/sciadv.adg8631
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author Kasamatsu, Shingo
Nishimura, Akira
Alam, Md. Morshedul
Morita, Masanobu
Shimoda, Kakeru
Matsunaga, Tetsuro
Jung, Minkyung
Ogata, Seiryo
Barayeu, Uladzimir
Ida, Tomoaki
Nishida, Motohiro
Nishimura, Akiyuki
Motohashi, Hozumi
Akaike, Takaaki
author_facet Kasamatsu, Shingo
Nishimura, Akira
Alam, Md. Morshedul
Morita, Masanobu
Shimoda, Kakeru
Matsunaga, Tetsuro
Jung, Minkyung
Ogata, Seiryo
Barayeu, Uladzimir
Ida, Tomoaki
Nishida, Motohiro
Nishimura, Akiyuki
Motohashi, Hozumi
Akaike, Takaaki
author_sort Kasamatsu, Shingo
collection PubMed
description Abundant formation of endogenous supersulfides, which include reactive persulfide species and sulfur catenated residues in thiols and proteins (supersulfidation), has been observed. We found here that supersulfides catalyze S-nitrosoglutathione (GSNO) metabolism via glutathione-dependent electron transfer from aldehydes by exploiting alcohol dehydrogenase 5 (ADH5). ADH5 is a highly conserved bifunctional enzyme serving as GSNO reductase (GSNOR) that down-regulates NO signaling and formaldehyde dehydrogenase (FDH) that detoxifies formaldehyde in the form of glutathione hemithioacetal. C174S mutation significantly reduced the supersulfidation of ADH5 and almost abolished GSNOR activity but spared FDH activity. Notably, Adh5(C174S/C174S) mice manifested improved cardiac functions possibly because of GSNOR elimination and consequent increased NO bioavailability. Therefore, we successfully separated dual functions (GSNOR and FDH) of ADH5 (mediated by the supersulfide catalysis) through the biochemical analysis for supersulfides in vitro and characterizing in vivo phenotypes of the GSNOR-deficient organisms that we established herein. Supersulfides in ADH5 thus constitute a substantial catalytic center for GSNO metabolism mediating electron transfer from aldehydes.
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spelling pubmed-104384542023-08-19 Supersulfide catalysis for nitric oxide and aldehyde metabolism Kasamatsu, Shingo Nishimura, Akira Alam, Md. Morshedul Morita, Masanobu Shimoda, Kakeru Matsunaga, Tetsuro Jung, Minkyung Ogata, Seiryo Barayeu, Uladzimir Ida, Tomoaki Nishida, Motohiro Nishimura, Akiyuki Motohashi, Hozumi Akaike, Takaaki Sci Adv Biomedicine and Life Sciences Abundant formation of endogenous supersulfides, which include reactive persulfide species and sulfur catenated residues in thiols and proteins (supersulfidation), has been observed. We found here that supersulfides catalyze S-nitrosoglutathione (GSNO) metabolism via glutathione-dependent electron transfer from aldehydes by exploiting alcohol dehydrogenase 5 (ADH5). ADH5 is a highly conserved bifunctional enzyme serving as GSNO reductase (GSNOR) that down-regulates NO signaling and formaldehyde dehydrogenase (FDH) that detoxifies formaldehyde in the form of glutathione hemithioacetal. C174S mutation significantly reduced the supersulfidation of ADH5 and almost abolished GSNOR activity but spared FDH activity. Notably, Adh5(C174S/C174S) mice manifested improved cardiac functions possibly because of GSNOR elimination and consequent increased NO bioavailability. Therefore, we successfully separated dual functions (GSNOR and FDH) of ADH5 (mediated by the supersulfide catalysis) through the biochemical analysis for supersulfides in vitro and characterizing in vivo phenotypes of the GSNOR-deficient organisms that we established herein. Supersulfides in ADH5 thus constitute a substantial catalytic center for GSNO metabolism mediating electron transfer from aldehydes. American Association for the Advancement of Science 2023-08-18 /pmc/articles/PMC10438454/ /pubmed/37595031 http://dx.doi.org/10.1126/sciadv.adg8631 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Kasamatsu, Shingo
Nishimura, Akira
Alam, Md. Morshedul
Morita, Masanobu
Shimoda, Kakeru
Matsunaga, Tetsuro
Jung, Minkyung
Ogata, Seiryo
Barayeu, Uladzimir
Ida, Tomoaki
Nishida, Motohiro
Nishimura, Akiyuki
Motohashi, Hozumi
Akaike, Takaaki
Supersulfide catalysis for nitric oxide and aldehyde metabolism
title Supersulfide catalysis for nitric oxide and aldehyde metabolism
title_full Supersulfide catalysis for nitric oxide and aldehyde metabolism
title_fullStr Supersulfide catalysis for nitric oxide and aldehyde metabolism
title_full_unstemmed Supersulfide catalysis for nitric oxide and aldehyde metabolism
title_short Supersulfide catalysis for nitric oxide and aldehyde metabolism
title_sort supersulfide catalysis for nitric oxide and aldehyde metabolism
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10438454/
https://www.ncbi.nlm.nih.gov/pubmed/37595031
http://dx.doi.org/10.1126/sciadv.adg8631
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