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

Sorg, Olivier; Tran, Christian; Carraux, Pierre; Grand, Denise; Barraclough, Christelle; Arrighi, Jean-François; Descombes, Patrick; Piguet, Vincent; Saurat, Jean-Hilaire

doi:10.1038/sj.jid.5701106

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Title		Metabolism and biological activities of topical 4-oxoretinoids in mouse skin
Authors		Sorg, Olivier Tran, Christian Carraux, Pierre Grand, Denise Barraclough, Christelle Arrighi, Jean-François Descombes, Patrick Piguet, Vincent Saurat, Jean-Hilaire show all authors [1 - 9]
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		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
Identifiers		DOI: 10.1038/sj.jid.5701106 PMID: 17943179
Full text		Article (Accepted version) (3.6 MB) - Limited access to UNIGE Other version: http://www.nature.com/jid/journal/v128/n4/full/5701106a.html
Structures		Faculté des sciences / Section de biologie / Département de génétique et évolution Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Research groups		La recherche en biochimie dermatologique (652) Rôle du CD44 (809)
Citation (ISO format)		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