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Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage

During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We...

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Autores principales: Olsson, Magnus G., Allhorn, Maria, Larsson, Jörgen, Cederlund, Martin, Lundqvist, Katarina, Schmidtchen, Artur, Sørensen, Ole E., Mörgelin, Matthias, Åkerström, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214066/
https://www.ncbi.nlm.nih.gov/pubmed/22096585
http://dx.doi.org/10.1371/journal.pone.0027505
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author Olsson, Magnus G.
Allhorn, Maria
Larsson, Jörgen
Cederlund, Martin
Lundqvist, Katarina
Schmidtchen, Artur
Sørensen, Ole E.
Mörgelin, Matthias
Åkerström, Bo
author_facet Olsson, Magnus G.
Allhorn, Maria
Larsson, Jörgen
Cederlund, Martin
Lundqvist, Katarina
Schmidtchen, Artur
Sørensen, Ole E.
Mörgelin, Matthias
Åkerström, Bo
author_sort Olsson, Magnus G.
collection PubMed
description During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(−6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.
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spelling pubmed-32140662011-11-17 Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage Olsson, Magnus G. Allhorn, Maria Larsson, Jörgen Cederlund, Martin Lundqvist, Katarina Schmidtchen, Artur Sørensen, Ole E. Mörgelin, Matthias Åkerström, Bo PLoS One Research Article During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(−6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding. Public Library of Science 2011-11-11 /pmc/articles/PMC3214066/ /pubmed/22096585 http://dx.doi.org/10.1371/journal.pone.0027505 Text en Olsson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Olsson, Magnus G.
Allhorn, Maria
Larsson, Jörgen
Cederlund, Martin
Lundqvist, Katarina
Schmidtchen, Artur
Sørensen, Ole E.
Mörgelin, Matthias
Åkerström, Bo
Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage
title Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage
title_full Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage
title_fullStr Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage
title_full_unstemmed Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage
title_short Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage
title_sort up-regulation of a1m/α(1)-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214066/
https://www.ncbi.nlm.nih.gov/pubmed/22096585
http://dx.doi.org/10.1371/journal.pone.0027505
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