Document Detail


Retinol dehydrogenase 10 but not retinol/sterol dehydrogenase(s) regulates the expression of retinoic acid-responsive genes in human transgenic skin raft culture.
MedLine Citation:
PMID:  21345790     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retinoic acid is essential for skin growth and differentiation, and its concentration in skin is controlled tightly. In humans, four different members of the short-chain dehydrogenase/reductase (SDR) superfamily of proteins were proposed to catalyze the rate-limiting step in the biosynthesis of retinoic acid (the oxidation of retinol to retinaldehyde). Epidermis contains at least three of these enzymes, but their relative importance for retinoic acid biosynthesis and regulation of gene expression during growth and differentiation of epidermis is not known. Here, we investigated the effect of the four human SDRs on retinoic acid biosynthesis, and their impact on growth and differentiation of keratinocytes using organotypic skin raft culture model of human epidermis. The results of this study demonstrate that ectopic expression of retinol dehydrogenase 10 (RDH10, SDR16C4) in skin rafts dramatically increases proliferation and inhibits differentiation of keratinocytes, consistent with the increased steady-state levels of retinoic acid and activation of retinoic acid-inducible genes in RDH10 rafts. In contrast, SDRs with dual retinol/sterol substrate specificity, namely retinol dehydrogenase 4 (RoDH4, SDR9C8), RoDH-like 3α-hydroxysteroid dehydrogenase (RL-HSD, SDR9C6), and RDH-like SDR (RDHL, SDR9C4) do not affect the expression of retinoic acid-inducible genes but alter the expression levels of several components of extracellular matrix. These results reveal essential differences in the metabolic contribution of RDH10 versus retinol/sterol dehydrogenases to retinoic acid biosynthesis and provide the first evidence that non-retinoid metabolic products of retinol/sterol dehydrogenases affect gene expression in human epidermis.
Authors:
Seung-Ah Lee; Olga V Belyaeva; Lizhi Wu; Natalia Y Kedishvili
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-02-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-11     Completed Date:  2011-06-28     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13550-60     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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MeSH Terms
Descriptor/Qualifier:
3-Hydroxysteroid Dehydrogenases / biosynthesis*,  genetics
Alcohol Oxidoreductases / biosynthesis*,  genetics
Epidermis / cytology,  enzymology*
Gene Expression Regulation, Enzymologic / drug effects,  physiology*
Humans
Keratolytic Agents / metabolism,  pharmacology
Male
Tissue Culture Techniques
Tretinoin / metabolism*,  pharmacology
Grant Support
ID/Acronym/Agency:
AA12153/AA/NIAAA NIH HHS; P30 AR50948/AR/NIAMS NIH HHS; P30 CA13148/CA/NCI NIH HHS; P30 DK079337/DK/NIDDK NIH HHS; P50 AT00477/AT/NCCAM NIH HHS; RR19231/RR/NCRR NIH HHS; U54 CA100949/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Keratolytic Agents; 302-79-4/Tretinoin; EC 1.1.-/3-Hydroxysteroid Dehydrogenases; EC 1.1.-/Alcohol Oxidoreductases; EC 1.1.-/DHRS9 protein, human; EC 1.1.1.-/trans-retinol dehydrogenase
Comments/Corrections

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