Retinol Research Today is a free monthly online journal that collates and summarizes the latest research about Retinol, including details on vitamin a, uses, wrinkle treatment, anti-aging.

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

Sorg O, Tran C, Carraux P, Grand D, Barraclough C, Arrighi JF, Descombes P, Piguet V, Saurat JH

Department of Dermatology, University Hospital, Geneva, Switzerland. olivier.sorg@hcuge.ch

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.

Published 13 March 2008 in J Invest Dermatol, 128(4): 999-1008.
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Articles on Retinol published 13 March 2008:

All-trans retinoic acid-induced hyaluronan production and hyperplasia are partly mediated by EGFR signaling in epidermal keratinocytes.   J Invest Dermatol, 128(4): 797-807.

All-trans retinoic acid (RA) compromises epidermal differentiation and causes keratinocyte hyperproliferation through mechanisms not completely understood, but may involve the regulatory matrix molecule hyaluronan. In this work, the influences of all-trans RA on epidermal morphology and hyaluronan metabolism were examined in organotypic and monolayer cultures of rat epidermal keratinocytes (REKs). All-trans RA treatment of organotypic REK cultures (10 days) increased the synthesis of ... [Abstract] [Full-text]

Retinol decreases phosphatidylinositol 3-kinase activity in colon cancer cells.   Mol Carcinog, 47(4): 264-74.

Previously, we showed that retinol inhibited all-trans-retinoic acid (ATRA)-resistant human colon cancer cell invasion via a retinoic acid receptor-independent mechanism. Because phosphatidylinositol 3-kinase (PI3K) regulates cell invasion, the objective of the current study was to determine if retinol affected PI3K activity. Following 24 h of serum starvation, the ATRA resistant human colon cancer cell lines HCT-116 and SW620 were treated with 0, 1, or 10 microM retinol. Thirty minutes of ... [Abstract] [Full-text]

Articles on Retinol published 10 March 2008:

Retinoic acid regulation of the Mesp-Ripply feedback loop during vertebrate segmental patterning.   Dev Biol, 315(2): 317-30.

The Mesp bHLH genes play a conserved role during segmental patterning of the mesoderm in the vertebrate embryo by specifying segmental boundaries and anteroposterior (A-P) segmental polarity. Here we use a xenotransgenic approach to compare the transcriptional enhancers that drive expression of the Mesp genes within segments of the presomitic mesoderm (PSM) of different vertebrate species. We find that the genomic sequences upstream of the mespb gene in the pufferfish Takifugu rubripes ... [Abstract] [Full-text]

CYP26A1 knockout embryonic stem cells exhibit reduced differentiation and growth arrest in response to retinoic acid.   Dev Biol, 315(2): 331-54.

CYP26A1, a cytochrome P450 enzyme, metabolizes all-trans-retinoic acid (RA) into polar metabolites, e.g. 4-oxo-RA and 4-OH-RA. To determine if altering RA metabolism affects embryonic stem (ES) cell differentiation, we disrupted both alleles of Cyp26a1 by homologous recombination. CYP26a1(-/-) ES cells had a 11.0+/-3.2-fold higher intracellular RA concentration than Wt ES cells after RA treatment for 48 h. RA-treated CYP26A1(-/-) ES cells exhibited 2-3 fold higher mRNA levels of Hoxa1, a ... [Abstract] [Full-text]

Role of the translational repressor 4E-BP1 in the regulation of p21(Waf1/Cip1) expression by retinoids.   Biochem Biophys Res Commun, 368(4): 983-9.

The mechanisms by which retinoids regulate initiation of mRNA translation for proteins that mediate their biological effects are not known. We have previously shown that all-trans-retinoic acid (ATRA) induces mTOR-mediated activation of the p70 S6 kinase, suggesting the existence of a mechanism by which retinoids may regulate mRNA translation. We now demonstrate that treatment of acute promyelocytic leukemia (APL)-derived NB4 cells with ATRA results in dissociation of the translational ... [Abstract] [Full-text]

Articles on Retinol published 6 March 2008:

Alitretinoin: a comprehensive review.   Expert Opin Investig Drugs, 17(3): 437-43.

BACKGROUND: Alitretinoin (9-cis-retinoic acid) is a unique panagonist retinoid, capable of binding to all six known retinoid receptors (RAR-alpha, -beta, -gamma, and RXR-alpha, -beta, -gamma). Studies are being carried out to determine how best to utilize this characteristic in treatments for conditions such as chronic hand dermatitis. OBJECTIVE: To review the literature on alitretinoin. METHODS: The scope of the review encompasses ways that alitretinoin is currently and may potentially be ... [Abstract] [Full-text]

Ab initio fragment molecular orbital study of molecular interactions between liganded retinoid X receptor and its coactivator; part II: influence of mutations in transcriptional activation function 2 activating domain core on the molecular interactions.   J Phys Chem A, 112(10): 1986-98.

The ab initio fragment molecular orbital (FMO) calculations were performed for retinoid X receptor (RXR) complexes with its ligand 9-cis retinoic acid (9cRA) and steroid receptor coactivator-1 (SRC1) to examine the influence of mutations in transcriptional activation function 2 activating domain core (AF2C) of RXR on molecular interactions between 9cRA liganded RXR and SRC1 coactivator. The RXR-SRC1 interactions in three types of RXR-9cRA-SRC1 complexes, namely, a wild type (WT), a mutant whose ... [Abstract] [Full-text]

Articles on Retinol published 28 February 2008:

Retinoic acid- and phorbol ester-induced neuronal differentiation down-regulates caveolin expression in GnRH neurons.   J Neurochem, 104(6): 1577-87.

GN11 and GT1-7 are immortalized gonadotropin-releasing hormone-positive murine cell lines exhibiting the features of immature olfactory neurons and differentiated hypothalamic neurons, respectively. Using electron microscopy and biochemical assays (RT-PCR and immunoblotting) we determined the presence of numerous caveolae invaginations and of caveolin-1 and -2 mRNAs and proteins in GN11 cells, and their absence in GT1-7 cells. The lack of caveolins in GT1-7 cells might be due to the silencing ... [Abstract] [Full-text]

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