Document Detail


Metabolism and biological activities of topical 4-oxoretinoids in mouse skin.
MedLine Citation:
PMID:  17943179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article     Date:  2007-10-18
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  128     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-13     Completed Date:  2008-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  999-1008     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University Hospital, Geneva, Switzerland. olivier.sorg@hcuge.ch
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MeSH Terms
Descriptor/Qualifier:
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:
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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