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

Article Article scientifique Article Metabolism and biological activities of topical 4-oxoretinoids in mouse skin eng 2008 author Sorg Olivier 32172 author Tran Christian author Carraux Pierre author Grand Denise author Barraclough Christelle 135627 author Arrighi Jean-François 28404 author Descombes Patrick 24132 author Piguet Vincent 84926 author Saurat Jean-Hilaire 21995 999-1008 10.1038/sj.jid.5701106 17943179 0022-202X http://www.nature.com/jid/journal/v128/n4/full/5701106a.html 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. Animals Dendritic Cells/drug effects/metabolism Epidermis/drug effects/metabolism/pathology Gene Expression/drug effects Humans Hyperplasia/chemically induced Lipid Peroxidation/drug effects Mice Peroxidase/metabolism Retinaldehyde/analogs & derivatives/chemistry/metabolism/pharmacology Retinoids/pharmacology Skin/drug effects/metabolism/pathology Tail Vitamin A/analogs & derivatives/chemistry/metabolism/pharmacology Dewey 616 Dewey 616.8 Dewey 590 44 Département de génétique et évolution 162 54 Département de microbiologie et médecine moléculaire 21B 61 Département des neurosciences cliniques 226 false 386 La recherche en biochimie dermatologique 652 478 Rôle du CD44 809 Journal of investigative dermatology 128 4 ff6d010a-ef1a-4f0d-9d80-51a72316a203 Article (Accepted version) Restricted 17943179.pdf 3724105 application/pdf restrictedAccess Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

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Metabolism and biological activities of topical 4-oxoretinoids in mouse skin	Journal of investigative dermatology			2008	667	2

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Barraclough, Christelle