Peroxidasin-mediated crosslinking of collagen IV is independent of NADPH oxidases

Collagen IV is a major component of the basement membrane in epithelial tissues. The NC1 domains of collagen IV protomers are covalently linked together through sulfilimine bonds, the formation of which is catalyzed by peroxidasin. Although hydrogen peroxide is essential for this reaction, the exact...

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Bibliographic Details
Published in:Redox biology 2018-06, Vol.16, p.314-321
Main Authors: Sirokmány, Gábor, Kovács, Hajnal A., Lázár, Enikő, Kónya, Krisztina, Donkó, Ágnes, Enyedi, Balázs, Grasberger, Helmut, Geiszt, Miklós
Format: Article
Language:English
Subjects:
Basement Membrane - metabolism
Catalysis
Cell Line
Collagen IV
Collagen Type IV - metabolism
Dual Oxidases - metabolism
Epithelial Cells - metabolism
Extracellular Matrix
Extracellular Matrix Proteins - metabolism
Humans
Hydrogen peroxide
Hydrogen Peroxide - metabolism
NADPH oxidase
NADPH Oxidases - metabolism
Oxygen - metabolism
Peroxidase - metabolism
Peroxidasin
Research Paper
Sulfilimine
Superoxides - metabolism
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Summary:Collagen IV is a major component of the basement membrane in epithelial tissues. The NC1 domains of collagen IV protomers are covalently linked together through sulfilimine bonds, the formation of which is catalyzed by peroxidasin. Although hydrogen peroxide is essential for this reaction, the exact source of the oxidant remains elusive. Members of the NOX/DUOX NADPH oxidase family are specifically devoted to the production of superoxide and hydrogen peroxide. Our aim in this study was to find out if NADPH oxidases contribute in vivo to the formation of collagen IV sulfilimine crosslinks. We used multiple genetically modified in vivo model systems to provide a detailed assessment of this question. Our data indicate that in various peroxidasin-expressing tissues sulfilimine crosslinks between the NC1 domains of collagen IV can be readily detected in the absence of functioning NADPH oxidases. We also analyzed how subatmospheric oxygen levels influence the collagen IV network in collagen-producing cultured cells with rapid matrix turnover. We showed that collagen IV crosslinks remain intact even under strongly hypoxic conditions. Our hypothesis is that during collagen IV network formation PXDN cooperates with a NOX/DUOX-independent H2O2 source that is functional also at very low ambient oxygen levels.
ISSN:2213-2317
2213-2317
DOI:10.1016/j.redox.2018.03.009