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

Autor: Katarina Lundqvist, Magnus G. Olsson, Ole E. Sørensen, Bo Åkerström, Maria Allhorn, Artur Schmidtchen, Matthias Mörgelin, Jörgen Larsson, Martin Cederlund
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Keratinocytes
Cytoplasm
Anatomy and Physiology
Gene Expression
lcsh:Medicine
medicine.disease_cause
Oxygen
Protein Carbonylation
chemistry.chemical_compound
Molecular Cell Biology
Signaling in Cellular Processes
lcsh:Science
Heme
Cells
Cultured
Cytoskeleton
Skin
Cellular Stress Responses
chemistry.chemical_classification
Multidisciplinary
Cell Death
integumentary system
Immunohistochemistry
Cellular Structures
Signaling Cascades
Extracellular Matrix
Dermatology and Venereal Diseases
medicine.anatomical_structure
Biochemistry
Medicine
Keratinocyte
Research Article
Signal Transduction
Infectious Medicine
Cell Survival
Radioimmunoassay
chemistry.chemical_element
Oxidative phosphorylation
Dermatology
Real-Time Polymerase Chain Reaction
Collagen Type I
Microscopy
Electron
Transmission
Alpha-Globulins
medicine
Extracellular
Humans
Biology
Reactive oxygen species
lcsh:R
Oxidative Stress
chemistry
Subcellular Organelles
lcsh:Q
Hemoglobin
Reactive Oxygen Species
Oxidative stress
Zdroj: PLoS ONE; 6(11), no e27505 (2011)
PLoS ONE, Vol 6, Iss 11, p e27505 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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