A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans
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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Cites
Fas-Induced Caspase Denitrosylation
Mannick, J. B., Hausladen, A., Liu, L., Hess, D. T., Zeng, M., Miao, Q., Kane, L. S., Gow, A. J., & Stamler, J. S. (1999) · Science · doi:10.1126/science.284.5414.651 · Cited by 743 · see citing works
Self-citationEndogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways.
Gaston, B. M., Reilly, J., Drazen, J. M., Fackler, J. C., Ramdev, P., Arnelle, D. R., Mullins, M. E., Sugarbaker, D. J., Chee, C., Singel, D. J., et al. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10957 · Cited by 620 · see citing works
Self-citationNikitovic, D., & Holmgren, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19180 · Cited by 368 · see citing works
Nitrosative Stress: Activation of the Transcription Factor OxyR
Hausladen, A., Privalle, C. T., Keng, T., DeAngelo, J., & Stamler, J. S. (1996) · Cell · doi:10.1016/s0092-8674(00)80147-6 · Cited by 359 · see citing works
Self-citationThe chemistry of the <i>S</i> -nitrosoglutathione/glutathione system
Singh, S. P., Wishnok, J. S., Keshive, M., Deen, W. M., & Tannenbaum, S. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14428 · Cited by 336 · see citing works
Reversible Binding of Nitric Oxide by a Salivary Heme Protein from a Bloodsucking Insect
Ribeiro, J. M. C., Hazzard, J. M. H., Nussenzveig, R. H., Champagne, D. E., & Walker, F. A. (1993) · Science · doi:10.1126/science.8386393 · Cited by 311 · see citing works
Nitrosative stress: Metabolic pathway involving the flavohemoglobin
Hausladen, A., Gow, A. J., & Stamler, J. S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14100 · Cited by 285 · see citing works
Self-citationS-Nitrosoglutathione is a substrate for rat alcohol dehydrogenase class III isoenzyme
Jensen, D. E., Belka, G. K., & Bois, G. C. D. (1998) · Biochemical Journal · doi:10.1042/bj3310659 · Cited by 282 · see citing works
Ascaris haemoglobin is a nitric oxide-activated ‘deoxygenase’
Minning, D. M., Gow, A. J., Bonaventura, J., Braun, R. D., Dewhirst, M. W., Goldberg, D. E., & Stamler, J. S. (1999) · Nature · doi:10.1038/46822 · Cited by 217 · see citing works
Self-citationA New Pathway of Nitric Oxide/Cyclic GMP Signaling InvolvingS-Nitrosoglutathione
Mayer, B., Pfeiffer, S., Schrammel, A., Koesling, D., Schmidt, K., & Brünner, F. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3264 · Cited by 200 · see citing works
Xanthine Oxidase-mediated Decomposition of S-Nitrosothiols
Trujillo, M., Álvarez, M. N., Peluffo, G., Freeman, B. Α., & Radí, R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.14.7828 · Cited by 192 · see citing works
Protection from nitrosative stress by yeast flavohemoglobin
Liu, L., Zeng, M., Hausladen, A., Heitman, J., & Stamler, J. S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090083597 · Cited by 190 · see citing works
Self-citationHomocysteine Antagonism of Nitric Oxide-Related Cytostasis in Salmonella typhimurium
Groote, M. A. D., Testerman, T. L., Xu, Y., Stauffer, G. V., & Fang, F. C. (1996) · Science · doi:10.1126/science.272.5260.414 · Cited by 183 · see citing works
An Apoptotic Model for Nitrosative Stress
Eu, J. P., Liu, L., Zeng, M., & Stamler, J. S. (2000) · Biochemistry · doi:10.1021/bi992046e · Cited by 182 · see citing works
Self-citationKluge, I., Gutteck‐Amsler, U., Zollinger, M., & Kim, Q. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69062599.x · Cited by 174 · see citing works
Shen, S.-G., Sulter, G. J., Jeffries, T. W., & Cregg, J. M. (1998) · Gene · doi:10.1016/s0378-1119(98)00315-1 · Cited by 160 · see citing works
Hemoglobin induction in mouse macrophages
Liu, L., Zeng, M., & Stamler, J. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.12.6643 · Cited by 159 · see citing works
Self-citationSeleno Compounds and Glutathione Peroxidase Catalyzed Decomposition ofS-Nitrosothiols
Hou, Y., Guo, Z., Li, J., & Wang, P. G. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1620 · Cited by 153 · see citing works
Catalysis by Cu2+ of nitric oxide release from S-nitrosothiols (RSNO)
Askew, S. C., Barnett, D. J., McAninly, J., & Williams, D. L. H. (1995) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/p29950000741 · Cited by 136 · see citing works
S-Nitrosoglutathione as a substrate for γ-glutamyl transpeptidase
Hogg, N., Singh, R., Konorev, E. A., Joseph, J., & Kalyanaraman, B. (1997) · Biochemical Journal · doi:10.1042/bj3230477 · Cited by 136 · see citing works
Scorza, G., Pietraforte, D., & Minetti, M. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00378-4 · Cited by 132 · see citing works
Broderick, J. B. (2001) · Encyclopedia of Life Sciences · doi:10.1038/npg.els.0000631 · Cited by 125 · see citing works
Rucker, R. B., & Chowanadisai, W. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-384947-2.00181-1 · Cited by 109 · see citing works
Gutheil, W. G., Holmquist, B., & Vallée, B. L. (1992) · Biochemistry · doi:10.1021/bi00117a025 · Cited by 101 · see citing works
Weimer, E. P., Rao, E., & Brendel, M. (1993) · Molecular and General Genetics MGG · doi:10.1007/bf00279438 · Cited by 98 · see citing works
Ras, J., OPHEM, P. W. V., Reijnders, W. N. M., et al. (1995) · Journal of Bacteriology · doi:10.1128/jb.177.1.247-251.1995 · Cited by 82 · see citing works
Akaike, T., Inoue, K., Okamoto, T., Nishino, H., Otagiri, M., Fujii, S., & Maeda, H. (1997) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021774 · Cited by 79 · see citing works
Shafqat, J., El-Ahmad, M., Danielsson, O., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.11.5595 · Cited by 66 · see citing works
Barber, R. D., & Donohue, T. J. (1998) · Biochemistry · doi:10.1021/bi971463t · Cited by 60 · see citing works
The Reaction Rates of NO with Horseradish Peroxidase Compounds I and II
Glover, R. E., Koshkin, V., Dunford, H. B., et al. (1999) · Nitric Oxide · doi:10.1006/niox.1999.0256 · Cited by 48 · see citing works
Studies on the Enzymatic Reduction of C-Nitroso Compounds1
Kuwada, M., Horie, S., & OGURA, Y. (1980) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a133040 · Cited by 12 · see citing works
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Hess, D. T., Matsumoto, A., Kim, S.-O., Marshall, H. E., & Stamler, J. S. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1569 · Cited by 2,153 · see citing works
Self-citationAntimicrobial reactive oxygen and nitrogen species: concepts and controversies
Fang, F. C. (2004) · Nature Reviews Microbiology · doi:10.1038/nrmicro1004 · Cited by 1,676 · see citing works
Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions
Lushchak, V. I. (2012) · Journal of Amino Acids · doi:10.1155/2012/736837 · Cited by 1,266 · see citing works
Stamler (2001) · doi:10.1016/s0092-8674(01)00495-0 · Cited by 1,261 · see citing works
Nitric oxide in health and disease of the respiratory system
Ricciardolo, F. L. M., Sterk, P. J., Gaston, B., & Folkerts, G. (2004) · Physiological Reviews · doi:10.1152/physrev.00034.2003 · Cited by 903 · see citing works
Redox-based regulation of signal transduction: principles, pitfalls, and promises
Janssen-Heininger, Y. M. W., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., & van der Vliet, A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.011 · Cited by 784 · see citing works
Self-citationSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
<i>S</i> -Nitrosylation in Cardiovascular Signaling
Lima, B., Forrester, M. T., Hess, D. T., & Stamler, J. S. (2010) · Circulation Research · doi:10.1161/circresaha.109.207381 · Cited by 490 · see citing works
Self-citationOxidative and nitrosative events in asthma
Andreadis, A. A., Hazen, S. L., Comhair, S. A. A., & Erzurum, S. C. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00278-8 · Cited by 327 · see citing works
Causes and consequences of cysteine S-glutathionylation
Grek, C. L., Zhang, J., Manevich, Y., Townsend, D. M., & Tew, K. D. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.461368 · Cited by 312 · see citing works
The chemical biology of S-nitrosothiols
Broniowska, K. A., & Hogg, N. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4590 · Cited by 259 · see citing works
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Zhang, Y., & Hogg, N. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.12.016 · Cited by 257 · see citing works
Yoon, S. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci24684 · Cited by 212 · see citing works
Nitric oxide and nitric oxide synthase isoforms in the normal, hypertrophic, and failing heart
Umar, S., & van der Laarse, A. (2010) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-009-0219-x · Cited by 182 · see citing works
Thioredoxin and Thioredoxin Reductase in Relation to Reversible <i>S</i> -Nitrosylation
Sengupta, R., & Holmgren, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4716 · Cited by 156 · see citing works
Nitric oxide and S-nitrosothiols in human blood
Giustarini, D., Milzani, A., Colombo, R., Dalle-Donne, I., & Rossi, R. (2003) · Clinica Chimica Acta · doi:10.1016/s0009-8981(03)00046-9 · Cited by 136 · see citing works
On the chemical biology of the nitrite/sulfide interaction
Cortese-Krott, M. M., Fernandez, B. O., Kelm, M., Butler, A. R., & Feelisch, M. (2015) · Nitric Oxide · doi:10.1016/j.niox.2014.12.009 · Cited by 115 · see citing works
The role of thioredoxin in the regulation of cellular processes by S-nitrosylation
Sengupta, R., & Holmgren, A. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.012 · Cited by 110 · see citing works
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Sha, Y., & Marshall, H. E. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.05.008 · Cited by 101 · see citing works
Staab, C. A., Ålander, J., Brandt, M., Lengqvist, J., Morgenstern, R., Grafström, R. C., & Höög, J.-O. (2008) · Biochemical Journal · doi:10.1042/bj20071666 · Cited by 89 · see citing works
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Nogueira, L., Figueiredo-Freitas, C., Casimiro-Lopes, G., Magdesian, M. H., Assreuy, J., & Sorenson, M. M. (2009) · Biochemical Journal · doi:10.1042/bj20091144 · Cited by 67 · see citing works
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Wolhuter, K., & Eaton, P. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.02.013 · Cited by 55 · see citing works
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Astuti, R. I., Watanabe, D., & Takagi, H. (2016) · Nitric Oxide · doi:10.1016/j.niox.2015.11.001 · Cited by 41 · see citing works
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López‐Sánchez, L. M., Muntané, J., de la Mata, M., & Rodríguez‐Ariza, A. (2009) · PROTEOMICS · doi:10.1002/pmic.200800546 · Cited by 35 · see citing works
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Risbano, M. G., & Gladwin, M. T. (2013) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-662-45805-1_13 · Cited by 32 · see citing works
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Leung, J., Wei, W., & Liu, L. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt031 · Cited by 12 · see citing works
Self-citation
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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