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

Gram, Magnus LU ; Allhorn, Maria LU ; Larsson, Jörgen G LU ; Cederlund, Martin LU ; Lundqvist, Katarina LU ; Schmidtchen, Artur LU ; Sørensen, Ole E LU ; Mörgelin, Matthias LU and Åkerström, Bo LU (2011) In PLoS One 6(11).
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS One
volume
6
issue
11
publisher
Public Library of Science
external identifiers
  • WOS:000297553900054
  • PMID:22096585
  • Scopus:80855133552
ISSN
1932-6203
DOI
10.1371/journal.pone.0027505
language
English
LU publication?
yes
id
4dd9319b-afde-494e-b064-eaae156efe64 (old id 2220633)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22096585?dopt=Abstract
date added to LUP
2011-12-02 22:10:25
date last changed
2016-10-13 04:33:27
@misc{4dd9319b-afde-494e-b064-eaae156efe64,
  abstract     = {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.},
  author       = {Gram, Magnus and Allhorn, Maria and Larsson, Jörgen G and Cederlund, Martin and Lundqvist, Katarina and Schmidtchen, Artur and Sørensen, Ole E and Mörgelin, Matthias and Åkerström, Bo},
  issn         = {1932-6203},
  language     = {eng},
  number       = {11},
  publisher    = {ARRAY(0x773f618)},
  series       = {PLoS One},
  title        = {Up-Regulation of A1M/α(1)-Microglobulin in Skin by Heme and Reactive Oxygen Species Gives Protection from Oxidative Damage.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0027505},
  volume       = {6},
  year         = {2011},
}