| Metabolism and biological activities of topical 4-oxoretinoids in mouse skin. | |
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MedLine Citation:
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PMID: 17943179 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Olivier Sorg; Christian Tran; Pierre Carraux; Denise Grand; Christelle Barraclough; Jean-François Arrighi; Patrick Descombes; Vincent Piguet; Jean-Hilaire Saurat |
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Publication Detail:
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Type: Journal Article Date: 2007-10-18 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 128 ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-03-13 Completed Date: 2008-04-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 999-1008 Citation Subset: IM |
Affiliation:
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Department of Dermatology, University Hospital, Geneva, Switzerland. olivier.sorg@hcuge.ch |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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 |
| Chemical | |
Reg. No./Substance:
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0/Retinoids; 11103-57-4/Vitamin A; 116-31-4/Retinaldehyde; 33532-44-4/4-oxoretinaldehyde; 62702-55-0/4-oxoretinol; EC 1.11.1.7/Peroxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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