Increased oxidative stress in the RAW 264.7 macrophage cell line is partially mediated via the S‐nitrosothiol‐induced inhibition of glutathione reductase
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We investigated whether endogenously or exogenously produced nitric oxide (NO) can inhibit cellular glutathione reductase (GR) via the formation of S‐nitrosothiols to decrease cellular glutathione (GSH) and increase oxidative stress in RAW 264.7 cells. The specificity of this inhibition was demonstrated by addition of a NO‐synthase inhibitor, and met‐ or oxyhemoglobin. Using isolated GR we found that only certain NO donors inhibit this enzyme via S‐nitrosothiol. Furthermore, we found that cellular GSH decrease is paralleled by an increase of superoxide anion production. Our results show that the GR enzyme is a potential target of S‐nitrosothiols to decrease cellular GSH levels and to induce oxidative stress in macrophages.
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In RAW264.7 cells, activation by a mixture of endotoxin and interferon-γ results in S-nitrosation of GR.
“In RAW264.7 cells, activation by a mixture of endotoxin and interferon-γ, a condition that increases endogenous NO production through the stimulation of inducible NOS (iNOS) in this macrophage-like cell line, results in S-nitrosation of GR.”
From Redox regulation of mitochondrial function (2012) · cites this paper as [59]
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- Authors
- Butzer, U., Weidenbach, H., Gansauge, S., Gansauge, F., Beger, H. G., & Nussler, A. K.
- Affiliations
- Universität Ulm (DE)
- Corresponding author
- Nussler, Andreas K
- ORCID
- Nussler, Andreas K
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 1999-02-26
- Volume
- 445
- Issue
- 2-3
- Pages
- 274-278
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2031297949
- Cited by
- 40
- References
- 25
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2021: 3 · 2020: 2 · 2019: 4 · 2013: 3
- FWCI
- 0.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Universität Ulm
- National Cancer Institute
- Topics
- 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
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- oxidative stress, glutathione reductase, S-nitrosothiols, nitric oxide, macrophages, RAW 264.7 macrophages, glutathione depletion, superoxide, nitric oxide synthase, enzyme inhibition
- MeSH terms
- Animals, Cell Line, Cysteine, Glutathione, Glutathione Reductase, Macrophages, Mercaptoethanol, Nitric Oxide, Nitroso Compounds, Superoxides, Reactive Oxygen Species, Oxidative Stress, S-Nitrosothiols, S-Nitrosoglutathione, Mice
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