Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Nitrite-mediated reduction of macrophage NADPH oxidase activity is dependent on xanthine oxidoreductase-derived nitric oxide but independent of S-nitrosation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
Show others and affiliations
2016 (English)In: Redox Biology, ISSN 0090-7324, E-ISSN 2213-2317, Vol. 10, p. 119-127Article in journal (Refereed) Published
Abstract [en]

Background: Inorganic nitrite has shown beneficial effects in cardiovascular and metabolic diseases partly via attenuation of NADPH-oxidase (NOX)-mediated oxidative stress. However, the exact mechanisms are still unclear. Here we investigated the role of S-nitrosation or altered expression of NOX subunits, and the role of xanthine oxidoreductase (XOR) in nitrite-derived nitric oxide (NO) production. Methods: Mouse macrophages were activated with LPS in the presence or absence of nitrite. NOX activity was measured by lucigenin-dependent chemiluminescence. Gene and protein expression of NOX2 subunits and XOR were investigated using qPCR and Western Blot. S-nitrosation of Nox2 and p22phox was studied with a Biotin Switch assay. Uric acid levels in cell culture medium were analyzed as a measure of XOR activity, and NO production was assessed by DAF-FM fluorescence. Results: NOX activity in activated macrophages was significantly reduced by nitrite. Reduced NOX activity was not attributed to decreased NOX gene expression. However, protein levels of p47phox and p67phox subunits were reduced by nitrite in activated macrophages. Protein expression of Nox2 and p22phox was not influenced by this treatment and neither was their S-nitrosation status. Increased uric acid levels after nitrite and diminished NO production during XOR-inhibition with febuxostat suggest that XOR is more active during nitrite-treatment of activated macrophages and plays an important role in the bioactivation of nitrite. Conclusions: Our findings contribute to the mechanistic understanding about the therapeutic effects associated with nitrite supplementation in many diseases. We show that nitrite-mediated inhibition of NOX activity cannot be explained by S-nitrosation of the NOX enzyme, but that changes in NOX2 expression and XOR function may contribute.

Place, publisher, year, edition, pages
2016. Vol. 10, p. 119-127
Keywords [en]
NADPH oxidase, Nitrite, Nitric oxide, Oxidative stress, S-nitrosation, Xanthine oxidoreductase
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-314055DOI: 10.1016/j.redox.2016.09.015ISI: 000390598800012PubMedID: 27744114OAI: oai:DiVA.org:uu-314055DiVA, id: diva2:1071658
Funder
Swedish Research Council, 521-2011-2639Swedish Heart Lung Foundation, 20110589 20140448Stockholm County Council, 2014-2015The Karolinska Institutet's Research Foundation, 2415/2012-225 2-3707/2013Available from: 2017-02-06 Created: 2017-01-26 Last updated: 2017-11-29Bibliographically approved

Open Access in DiVA

fulltext(1110 kB)85 downloads
File information
File name FULLTEXT01.pdfFile size 1110 kBChecksum SHA-512
6942e3d0d048216d6b3c5623a5e932ba9e623eb16cde7cf49d977e2dc2248d9480c864844ef256b29b5b7ba2b58fc195ae196329e71a526d6c013cc2328c4924
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Persson, A. Erik G.
By organisation
Department of Medical Cell Biology
In the same journal
Redox Biology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar
Total: 85 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 454 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf