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Metabolism and biological activities of topical 4-oxoretinoids in mouse skin

Tran, Christian
Carraux, Pierre
Grand, Denise
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Published in Journal of investigative dermatology. 2008, vol. 128, no. 4, p. 999-1008
Abstract Retinoic acid mediates most of the biological actions of vitamin A. It is oxidized by CYP26A1 to 4-oxoretinoic acid, considered as an inactive catabolite of retinoic acid. However, in the light of studies reporting the presence of 4-oxoretinal or 4-oxoretinol as the predominant retinoids during morphogenesis, we analyzed the retinoid-like biological activity of these oxoretinoids in mouse skin in vivo. Topical 4-oxoretinal and 4-oxoretinol promoted significant epidermal hyperplasia and metaplasia in mouse tail. They induced a moderate response for epidermal inflammation, compared with retinal, whereas neither 4-oxoretinal nor 4-oxoretinol prevented menadione-induced epidermal lipid peroxidation, unlike retinal and retinol. As analyzed by quantitative PCR, 4-oxoretinal and 4-oxoretinol did not reproduce the significant increased expression of genes coding for keratin 4, amphiregulin, heparin-EGF and CYP26A1, that did induce retinal and retinol. However, both retinal and 4-oxoretinal significantly inhibited the lipopolysaccharide-induced maturation of human dendritic cells in vitro. As analyzed in vivo and in vitro, 4-oxoretinal and 4-oxoretinol were not converted into retinoic acid. We conclude that 4-oxoretinal and 4-oxoretinol exert a moderate direct retinoid-like activity in vivo, thus confirming previous in vitro studies in amphibians showing 4-oxometabolites of vitamin A as bioactive agents rather than inactive catabolites.
Keywords AnimalsDendritic Cells/drug effects/metabolismEpidermis/drug effects/metabolism/pathologyGene Expression/drug effectsHumansHyperplasia/chemically inducedLipid Peroxidation/drug effectsMicePeroxidase/metabolismRetinaldehyde/analogs & derivatives/chemistry/metabolism/pharmacologyRetinoids/pharmacologySkin/drug effects/metabolism/pathologyTailVitamin A/analogs & derivatives/chemistry/metabolism/pharmacology
PMID: 17943179
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Research groups La recherche en biochimie dermatologique (652)
Rôle du CD44 (809)
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SORG, Olivier et al. Metabolism and biological activities of topical 4-oxoretinoids in mouse skin. In: Journal of investigative dermatology, 2008, vol. 128, n° 4, p. 999-1008. doi: 10.1038/sj.jid.5701106 https://archive-ouverte.unige.ch/unige:783

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Deposited on : 2009-02-12

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