The endogenous retinoid metaboliteS-4-oxo-9-cis-13,14-dihydro-retinoic acid activates retinoic acid receptor signalling bothin vitroandin vivo

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The endogenous retinoid metabolite S-4-oxo-9-cis-13,14-dihydro-retinoic acid activates retinoic acid receptor signalling both in vitro and in vivo.

Retinoic acid receptor (RAR) and retinoid X receptor are ligand-induced transcription factors that belong to the nuclear receptor family. The receptors are activated by small hydrophobic compounds, such as all-trans-retinoic acid and 9-cis-retinoic acid, respectively. Interestingly, these receptors are also targets for a number of exogenous compounds. In this study, we characterized the biologi...

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Effects of Novel Retinoic Acid Compound, 9-cis-Retinoic Acid, on Proliferation, Differentiation, and Expression of Retinoic Acid Receptor-a

Retinoic acid modulates proliferation and differentiation of a wide variety of normal and leukemic cells through two distinct families of transcriptional factors: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). A stereoisomer of retinoic acid, 9-cis-retinoic acid, is a highaffinity ligand for RXR and binds efficiently to RAR. In contrast, all-trans-retinoic acid interact...

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9-cis-retinoic acid inhibits androgen receptor activity through activation of retinoid X receptor.

Although the retinoic X receptor (RXR) forms heterodimers with many members of the estrogen receptor subfamily, the interaction between RXR and the members of the glucocorticoid receptor subfamily remains unclear. Here we show that the RXR can form a heterodimer with the androgen receptor (AR) under in vitro and in vivo conditions. Functional analyses further demonstrated that the AR, in the pr...

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Initial clinical trial of the retinoid receptor pan agonist 9-cis retinoic acid.

The retinoid response is mediated by families of nuclear receptors, the retinoic acid receptors (RARs), and the retinoid X receptors. All-trans retinoic acid (RA) binds only RARs and induces its own metabolism. In contrast, 9-cis RA is a newly identified agonist for both RARs and retinoid X receptors. We undertook a dose-ranging study to examine the safety, clinical tolerance, and pharmacokinet...

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Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid.

The discovery of the biological activity of 9-cis-retinoic acid raises questions as to its mode of biosynthesis. A simple mechanism involves the direct isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid. The concentrat...

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ژورنال

عنوان ژورنال: FEBS Journal

سال: 2009

ISSN: 1742-464X,1742-4658

DOI: 10.1111/j.1742-4658.2009.07023.x