Effect of Superoxide Dismutase on the Stability ofS-Nitrosothiols
Abstract
S-Nitrosothiols formed from the nitric oxide (NO)-dependent S-nitrosation of thiol-containing proteins and peptides such as albumin and glutathione (GSH) have been implicated in the transport, storage, and metabolism of NO in vivo. Recent data suggest that certain transition metals enhance the decomposition of S-nitrosothiols in vitro. The objective of this study was to determine what effect Cu, Zn superoxide dismutase (CuZn-SOD) has on the stability of certain S-nitrosothiols such as S-nitrosoglutathione (GSNO) in vitro. We found that CuZn-SOD (20 microM) but not Mn-SOD in the presence of GSH catalyzed the decomposition of GSNO with a Vmax of 6.7 +/- 0.4 microM/min and a Km of 5.6 +/- 0.5 microM at 37 degreesC. Increasing GSH concentrations with respect to CuZn-SOD resulted in complete decomposition of GSNO at concentrations of GSH:SOD of 2:1. Increasing GSH concentrations further from 0.1 to 10 mM resulted in a concentration-dependent attenuation in GSNO decomposition suggesting that SOD-catalyzed decomposition of GSNO would be maximal at concentrations of GSH known to be present in extracellular fluids (e.g., plasma). The decomposition of GSNO by CuZn-SOD resulted in the sustained production of NO. We propose that GSH reduces enzyme-associated Cu2+ to Cu1+ which mediates the reductive decomposition of the S-nitrosothiol to yield free NO. We conclude that CuZn-SOD may represent an important physiological modulator of steady-state concentrations of low-molecular-weight S-nitrosothiols in vivo.
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Enzymes such as CuZn-SOD or GPx can convert RSNO to NO in the presence of a reducing agent like GSH.
“Further, certain enzymes such as copper-containing superoxide dismutase (CuZn-SOD)140,176 or the selenium-containing enzyme glutathione peroxidase (GPx)140,171,173 can also convert RSNO to NO in the presence of a reducing agent, such as glutathione (GSH)”
From Recent advances in thromboresistant and antimicrobial polymers for biomedical applications: just say yes to nitric oxide (NO) (2016) · cites this paper as [176]
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- Authors
- Jourd'heuil, D., Laroux, F. S., Miles, A. M., Wink, D. A., & Grisham, M. B.
- Affiliations
- Louisiana State University (US)
- Grambling State University (US)
- National Cancer Institute (US)
- Corresponding author
- Grisham, Matthew B.
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 1999-01
- Volume
- 361
- Issue
- 2
- Pages
- 323-330
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W2050054971
- Cited by
- 123
- References
- 44
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 6 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 2 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 6 · 2012: 4
- FWCI
- 4.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk047663-06)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-47663, P01DK043785, DK-43785)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- superoxide dismutase, copper-zinc superoxide dismutase, S-nitrosothiols, S-nitrosoglutathione, glutathione, nitric oxide, S-nitrosylation, nitric oxide metabolism, copper reduction, manganese superoxide dismutase, thiol-containing proteins
- MeSH terms
- Catalysis, Cysteine, Glutathione, Humans, Nitroso Compounds, Serum Albumin, Bovine, Superoxide Dismutase, S-Nitrosothiols, S-Nitrosoglutathione
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