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Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat
The superoxide‐forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro‐atherosclerotic vascular phenotype. The hydrogen peroxide‐forming Nox4 afforded vascular protection, likely via NF‐E2‐related factor‐2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hy...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661235/ https://www.ncbi.nlm.nih.gov/pubmed/29084841 http://dx.doi.org/10.14814/phy2.13474 |
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author | Gajos‐Draus, Anna Duda, Monika Beręsewicz, Andrzej |
author_facet | Gajos‐Draus, Anna Duda, Monika Beręsewicz, Andrzej |
author_sort | Gajos‐Draus, Anna |
collection | PubMed |
description | The superoxide‐forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro‐atherosclerotic vascular phenotype. The hydrogen peroxide‐forming Nox4 afforded vascular protection, likely via NF‐E2‐related factor‐2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide‐forming Noxs, the downregulation of the Nox4/Nrf2 pathway. Guinea‐pigs and rats were studied either in winter or in summer, and the streptozotocin diabetic rats in winter. Plasma nitrite, and superoxide production by isolated hearts were measured, while frozen tissues served in biochemical analyses. Summer in both species and diabetes in rats downregulated myocardial Nox4 while reciprocally upregulating Nox2 and Nox5 in guinea‐pigs, and Nox2 in rats. Simultaneously, myocardial Nrf2 activity and the expression of the Nrf2‐directed heme oxygenase‐1 and endothelial NO synthase were reduced while activity of the nuclear factor κB (NF‐κB) and the expression of NF‐κB‐directed inducible NO synthase and the vascular cell adhesion molecule‐1 were increased. Cardiac superoxide production was increased while plasma nitrite was decreased reciprocally. Analogous disregulation of Noxs, Nrf2, and NF‐κB, occurred in diabetic rat kidneys. Given the diversity of the experimental settings and the uniform pattern of the responses, we speculate that: (1) chronic vascular oxidative stress is a nonspecific (model‐, species‐, organ‐independent) response involving the induction of Nox2 (and Nox5 in guinea‐pigs) and the NF‐κB pathway, and the repression of Nox4 and the Nrf2 pathway; and (2) the systems Nox2‐NF‐κB and Nox4‐Nrf2 regulate each other negatively. |
format | Online Article Text |
id | pubmed-5661235 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56612352017-11-01 Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat Gajos‐Draus, Anna Duda, Monika Beręsewicz, Andrzej Physiol Rep Original Research The superoxide‐forming NADPH oxidase homologues, Nox1, Nox2, and Nox5, seem to mediate the pro‐atherosclerotic vascular phenotype. The hydrogen peroxide‐forming Nox4 afforded vascular protection, likely via NF‐E2‐related factor‐2 (Nrf2) activation and/or Nox2 downregulation in transgenic mice. We hypothesized that oxidative stress in the intact vasculature involves, aside from the upregulation of the superoxide‐forming Noxs, the downregulation of the Nox4/Nrf2 pathway. Guinea‐pigs and rats were studied either in winter or in summer, and the streptozotocin diabetic rats in winter. Plasma nitrite, and superoxide production by isolated hearts were measured, while frozen tissues served in biochemical analyses. Summer in both species and diabetes in rats downregulated myocardial Nox4 while reciprocally upregulating Nox2 and Nox5 in guinea‐pigs, and Nox2 in rats. Simultaneously, myocardial Nrf2 activity and the expression of the Nrf2‐directed heme oxygenase‐1 and endothelial NO synthase were reduced while activity of the nuclear factor κB (NF‐κB) and the expression of NF‐κB‐directed inducible NO synthase and the vascular cell adhesion molecule‐1 were increased. Cardiac superoxide production was increased while plasma nitrite was decreased reciprocally. Analogous disregulation of Noxs, Nrf2, and NF‐κB, occurred in diabetic rat kidneys. Given the diversity of the experimental settings and the uniform pattern of the responses, we speculate that: (1) chronic vascular oxidative stress is a nonspecific (model‐, species‐, organ‐independent) response involving the induction of Nox2 (and Nox5 in guinea‐pigs) and the NF‐κB pathway, and the repression of Nox4 and the Nrf2 pathway; and (2) the systems Nox2‐NF‐κB and Nox4‐Nrf2 regulate each other negatively. John Wiley and Sons Inc. 2017-10-30 /pmc/articles/PMC5661235/ /pubmed/29084841 http://dx.doi.org/10.14814/phy2.13474 Text en © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Gajos‐Draus, Anna Duda, Monika Beręsewicz, Andrzej Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
title | Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
title_full | Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
title_fullStr | Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
title_full_unstemmed | Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
title_short | Cardiac and renal upregulation of Nox2 and NF‐κB and repression of Nox4 and Nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
title_sort | cardiac and renal upregulation of nox2 and nf‐κb and repression of nox4 and nrf2 in season‐ and diabetes‐mediated models of vascular oxidative stress in guinea‐pig and rat |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5661235/ https://www.ncbi.nlm.nih.gov/pubmed/29084841 http://dx.doi.org/10.14814/phy2.13474 |
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