title: Up-regulation of A1M/α1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage.
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.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. magnus_g.olsson@med.lu.se
authors.forename: Magnus G
authors.initials: MG
authors.lastname: Olsson
authors.forename: Maria
authors.initials: M
authors.lastname: Allhorn
authors.forename: Jörgen
authors.initials: J
authors.lastname: Larsson
authors.forename: Martin
authors.initials: M
authors.lastname: Cederlund
authors.forename: Katarina
authors.initials: K
authors.lastname: Lundqvist
authors.forename: Artur
authors.initials: A
authors.lastname: Schmidtchen
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Bo
authors.initials: B
authors.lastname: Akerström
mesh_terms: D000510:Alpha-Globulins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D006418:Heme / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation / Q000187:drug effects; D011863:Radioimmunoassay; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000510:Alpha-Globulins; D024042:Collagen Type I; D017382:Reactive Oxygen Species; C016001:alpha-1-microglobulin; D006418:Heme
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