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.

Acyclic retinoid inhibits angiogenesis by suppressing the MAPK pathway.

Komi Y, Sogabe Y, Ishibashi N, Sato Y, Moriwaki H, Shimokado K, Kojima S

Molecular Ligand Biology Research Team, Chemical Genomics Research Group, Chemical Biology Department, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.

Acyclic retinoid (ACR) is currently under clinical trial as an agent to suppress the recurrence of hepatocellular carcinoma (HCC) through its ability to induce apoptosis in premature HCC cells. ACR has an anticancer effect in vivo as well, although it shows weak apoptosis-inducing activity against mature HCC cells, suggesting the existence of an additional action mechanism. In this study, we investigated the antiangiogenic activity of ACR. ACR inhibited angiogenesis within chicken chorioallantoic membrane (CAM) in as similar a manner as all-trans retinoic acid (atRA). Although suppression of angiogenesis by atRA was partially rescued by the simultaneous addition of angiopoietin-1, suppression of angiogenesis by ACR was not rescued under the same condition at all. Conversely, although suppression of angiogenesis by ACR was partially inverted by the simultaneous addition of vascular endothelial growth factor (VEGF), suppression of angiogenesis by atRA was not affected under the same condition. These results suggested that mechanisms underlying the suppression of angiogenesis by ACR and atRA were different. ACR selectively inhibited the phosphorylation of VEGF receptor 2 (VEGFR2) and of extracellular signal-regulated kinase (ERK) without changing their protein expression levels, and inhibited endothelial cell growth, migration, and tube formation. The inhibition of the phosphorylation of ERK, endothelial growth, migration, tube formation, and angiogenesis by ACR was rescued by the overexpression of constitutively active mitogen-activated protein kinase (MAPK). Finally, ACR, but not atRA, inhibited HCC-induced angiogenesis in a xenografted CAM model. These results delineate the novel activity of ACR as an antiangiogenic through a strong inhibition of the VEGFR2 MAPK pathway.

Published 29 December 2009 in Lab Invest, 90(1): 52-60.
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Articles on Retinol published 21 December 2009:

Vitamin A intake and status in populations facing economic stress.   J Nutr, 140(1): 201S-7S.

Dietary quality and diversity reflect adequacy of vitamin A. Both can deteriorate in response to economic crises. Although the nutritional consequences of the 2008 world food price crisis remain unclear, past studies of diet, status, and socioeconomic standing under usual (deprived) and unusually disruptive times suggest dietary quality and vitamin A status decline in mothers and young children. This is presumably the result of shifting diets to include less preformed vitamin A-rich animal ... [Abstract] [Full-text]

The role of expanded coverage of the national vitamin A program in preventing morbidity and mortality among preschool children in India.   J Nutr, 140(1): 208S-12S.

Higher food prices increase the risk of vitamin A deficiency among preschool children in poor families, because a larger part of the household food budget is spent on grain foods and less on vitamin A-rich foods. Vitamin A supplementation is an important source of vitamin A for children. Our objective was to characterize coverage of the India national vitamin A program for preschool children and identify risk factors for not receiving vitamin A. Anthropometric and demographic data were examined ... [Abstract] [Full-text]

Articles on Retinol published 16 December 2009:

How I treat acute promyelocytic leukemia.   Blood, 114(25): 5126-35.

Acute promyelocytic leukemia is the first malignant disease highly curable with targeted therapy directed at a unique molecular abnormality. The characteristic bleeding diathesis is the most notorious manifestation of the disease, which historically has accounted for a high mortality rate during induction. Acute promyelocytic leukemia is one of the few hematologic diseases that must be recognized under the microscope by the practicing hematologist because early institution of all-trans retinoic ... [Abstract] [Full-text]

Articles on Retinol published 3 December 2009:

Retinol-binding site in interphotoreceptor retinoid-binding protein (IRBP): a novel hydrophobic cavity.   Invest Ophthalmol Vis Sci, 50(12): 5577-86.

PURPOSE: Interphotoreceptor retinoid-binding protein (IRBP) appears to target and protect retinoids during the visual cycle. X-ray crystallographic studies had noted a betabetaalpha-spiral fold shared with crotonases and C-terminal protein transferases. The shallow cleft formed by the fold was assumed to represent the retinol-binding site. However, a second hydrophobic site consisting of a highly restricted cavity was more recently appreciated during in silico ligand-docking studies. In this ... [Abstract] [Full-text]

Articles on Retinol published 30 November 2009:

NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5.   Biochem Biophys Res Commun, 390(4): 1186-91.

The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPARbeta/delta signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved ... [Abstract] [Full-text]

Articles on Retinol published 27 November 2009:

Vav1 and PU.1 are recruited to the CD11b promoter in APL-derived promyelocytes: role of Vav1 in modulating PU.1-containing complexes during ATRA-induced differentiation.   Exp Cell Res, 316(1): 38-47.

Vav1 plays an important role in the all-trans retinoic acid (ATRA)-induced completion of the differentiation program of acute promyelocytic leukemia (APL)-derived cells, in which it strengthens the drug effects and is involved in the regulation of maturation-related proteins, such as the CD11b surface antigen. In both myeloid and lymphoid cells, accumulating data attribute to the multidomain protein Vav1 a functional relevance in the control of gene expression, by direct interaction with ... [Abstract] [Full-text]

Articles on Retinol published 25 November 2009:

Activation of retinoic acid receptors by dihydroretinoids.   Mol Pharmacol, 76(6): 1228-37.

Vitamin A-derived metabolites act as ligands for nuclear receptors controlling the expression of a number of genes. Stereospecific saturation of the C(13)-C(14) double bond of all-trans-retinol by the enzyme, retinol saturase (RetSat), leads to the production of (R)-all-trans-13,14-dihydroretinol. In liver and adipose tissue, expression of RetSat is controlled by peroxisome proliferator-activated receptors (PPAR) alpha and gamma, respectively. Expression of RetSat in adipose tissue is also ... [Abstract] [Full-text]

Retinoic acid induces discrete Wnt-signaling-dependent differentiation in F9 cells.   Biochem Biophys Res Commun, 390(3): 564-9.

Retinoic acid (RA) induces F9 cells, the mouse teratocarcinoma cells, to differentiate into primitive endoderm and further into visceral and parietal endoderm depending on the culture conditions. To elucidate the instructive mechanisms involved in the differentiation steps we investigated the effects of Wnt-signaling members, Wnt3a and beta-catenin, on the differentiation of F9 cells and beta-catenin-deficient F9 cells (betaT cells). RA up-regulated the expression of differentiation markers for ... [Abstract] [Full-text]

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