4-Oxoretinol, a new natural ligand and transactivator of the retinoic acid receptors
| العنوان: | 4-Oxoretinol, a new natural ligand and transactivator of the retinoic acid receptors |
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| المؤلفون: | Jack Bolado, C C Achkar, Jochen Buck, Alexander W. Langston, Bruce Blumberg, Koji Nakanishi, Lorraine J. Gudas, J Speck, Fadila Derguini, Arthur A. Levin, Ronald M. Evans |
| المصدر: | Proceedings of the National Academy of Sciences. 93:4879-4884 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 1996. |
| سنة النشر: | 1996 |
| مصطلحات موضوعية: | Receptors, Retinoic Acid, Cellular differentiation, Retinoic acid, Gene Expression, Retinoid X receptor, Biology, Transfection, Cell Line, Mice, Retinoids, Xenopus laevis, chemistry.chemical_compound, Tumor Cells, Cultured, Animals, Humans, Vitamin A, Multidisciplinary, Retinoid X receptor alpha, Cell Differentiation, Stereoisomerism, Retinoid X receptor gamma, Retinoic acid receptor, P19 cell, chemistry, Biochemistry, Trans-Activators, Retinoid X receptor beta, Signal Transduction, Research Article |
| الوصف: | All-trans-retinoic acid (at-RA) induces cell differentiation in a wide variety of cell types, including F9 embryonic teratocarcinoma cells, and can influence axial pattern formation during embryonic development. We now identify a novel retinoid synthetic pathway in differentiating F9 cells that results in the intracellular production of 4-oxoretinol (4-oxo-ROL) from retinol (vitamin A). Approximately 10-15% of the total retinol in the culture is metabolized to 4-hydroxyretinol and 4-oxo-ROL by the at-RA-treated, differentiating F9 cells over an 18-hr period, but no detectable metabolism of all-trans-retinol to at-RA or 9-cis-retinoic acid is observed in these cells. Remarkably, we show that 4-oxo-ROL can bind and activate transcription of the retinoic acid receptors whereas all-trans-retinol shows neither activity. Low doses of 4-oxo-ROL (e.g., 10(-9) or 10(-10 M) can activate the retinoic acid receptors even though, unlike at-RA, 4-oxo-ROL does not contain an acid moiety at the carbon 15 position. 4-oxo-ROL does not bind or transcriptionally activate the retinoid X receptors. Treatment of F9 cells with 4-oxo-ROL induces differentiation without conversion to the acid and 4-oxo-ROL is active in causing axial truncation when administered to Xenopus embryos at the blastula stage. Thus, 4-oxo-ROL is a natural, biologically active retinoid that is present in differentiated F9 cells. Our data suggest that 4-oxo-ROL may be a novel signaling molecule and regulator of cell differentiation. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a8f9fffbe3c2e5121715a0f7fcad53c6 https://doi.org/10.1073/pnas.93.10.4879 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a8f9fffbe3c2e5121715a0f7fcad53c6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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