Cited by 913Redox biology and oxidative stressNitric Oxide and Endothelin EffectsSulfur Compounds in Biology

A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans

Liu, Limin, Hausladen, Alfred, Zeng, Ming, Que, Loretta, Heitman, Joseph, Stamler, Jonathan S.·2001·Nature

Abstract

Considerable evidence indicates that NO biology involves a family of NO-related molecules and that S-nitrosothiols (SNOs) are central to signal transduction and host defence. It is unknown, however, how cells switch off the signals or protect themselves from the SNOs produced for defence purposes. Here we have purified a single activity from Escherichia coli, Saccharomyces cerevisiae and mouse macrophages that metabolizes S-nitrosoglutathione (GSNO), and show that it is the glutathione-dependent formaldehyde dehydrogenase. Although the enzyme is highly specific for GSNO, it controls intracellular levels of both GSNO and S-nitrosylated proteins. Such 'GSNO reductase' activity is widely distributed in mammals. Deleting the reductase gene in yeast and mice abolishes the GSNO-consuming activity, and increases the cellular quantity of both GSNO and protein SNO. Furthermore, mutant yeast cells show increased susceptibility to a nitrosative challenge, whereas their resistance to oxidative stress is unimpaired. We conclude that GSNO reductase is evolutionarily conserved from bacteria to humans, is critical for SNO homeostasis, and protects against nitrosative stress.

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Crossref · 10.1038/35068596

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Authors
Liu, L., Hausladen, A., Zeng, M., Que, L., Heitman, J., & Stamler, J. S.
Affiliations
Howard Hughes Medical Institute (US)
Corresponding author
Stamler, Jonathan S.
Venue
Nature
Published
2001-03
Volume
410
Issue
6827
Pages
490-494
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W1488493608
Cited by
913
References
31
Citations by year
2026: 18 · 2025: 31 · 2024: 24 · 2023: 19 · 2022: 27 · 2021: 35 · 2020: 27 · 2019: 54 · 2018: 35 · 2017: 41 · 2016: 38 · 2015: 35 · 2014: 36 · 2013: 50 · 2012: 41
FWCI
12.95
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • U.S. Department of Energy
  • National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords
S-nitrosothiols, S-nitrosoglutathione, formaldehyde dehydrogenase, S-nitrosylation, nitric oxide signaling, nitrosative stress, glutathione, S-nitrosylated proteins, evolutionary conservation, Escherichia coli, Saccharomyces cerevisiae, macrophages, oxidative stress
MeSH terms
Aldehyde Oxidoreductases, Amino Acid Sequence, Animals, Cell Line, Escherichia coli, Glutathione, Humans, Macrophages, Mercaptoethanol, Molecular Sequence Data, Nitric Oxide, Nitro Compounds, Nitroso Compounds, Saccharomyces cerevisiae, Substrate Specificity, Conserved Sequence, Evolution, Molecular, S-Nitrosothiols, Mice

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