Novel Retinoic Acid Receptor Ligands in Xenopus Embryos
Retinoids are a large family of natural and synthetic compounds related to vitamin A that have pleiotropic effects on body physiology, reproduction, immunity, and embryonic development. The diverse activities of retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1996-05, Vol.93 (10), p.4873-4878 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Blumberg, Bruce Bolado, Jack Derguini, Fadila Craig, A. Grey Moreno, Tanya A. Chakravarti, Debabrata Heyman, Richard A. Buck, Jochen Evans, Ronald M. |
| description | Retinoids are a large family of natural and synthetic compounds related to vitamin A that have pleiotropic effects on body physiology, reproduction, immunity, and embryonic development. The diverse activities of retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the RARs and RXRs. Retinoic acids are thought to be the only natural ligands for these receptors and are widely assumed to be the active principle of vitamin A. However, during an unbiased, bioactivity-guided fractionation of Xenopus embryos, we were unable to detect significant levels of all-trans or 9-cis retinoic acids. Instead, we found that the major bioactive retinoid in the Xenopus egg and early embryo is 4-oxoretinaldehyde, which is capable of binding to and transactivating RARs. In addition to its inherent activity, 4-oxoretinaldehyde appears to be a metabolic precursor of two other RAR ligands, 4-oxoretinoic acid and 4-oxoretinol. The remarkable increase in activity of retinaldehyde and retinol as a consequence of 4-oxo derivatization suggests that this metabolic step could serve a critical regulatory function during embryogenesis. |
| doi_str_mv | 10.1073/pnas.93.10.4873 |
| format | Article |
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Grey ; Moreno, Tanya A. ; Chakravarti, Debabrata ; Heyman, Richard A. ; Buck, Jochen ; Evans, Ronald M.</creator><creatorcontrib>Blumberg, Bruce ; Bolado, Jack ; Derguini, Fadila ; Craig, A. Grey ; Moreno, Tanya A. ; Chakravarti, Debabrata ; Heyman, Richard A. ; Buck, Jochen ; Evans, Ronald M.</creatorcontrib><description>Retinoids are a large family of natural and synthetic compounds related to vitamin A that have pleiotropic effects on body physiology, reproduction, immunity, and embryonic development. The diverse activities of retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the RARs and RXRs. Retinoic acids are thought to be the only natural ligands for these receptors and are widely assumed to be the active principle of vitamin A. However, during an unbiased, bioactivity-guided fractionation of Xenopus embryos, we were unable to detect significant levels of all-trans or 9-cis retinoic acids. Instead, we found that the major bioactive retinoid in the Xenopus egg and early embryo is 4-oxoretinaldehyde, which is capable of binding to and transactivating RARs. In addition to its inherent activity, 4-oxoretinaldehyde appears to be a metabolic precursor of two other RAR ligands, 4-oxoretinoic acid and 4-oxoretinol. The remarkable increase in activity of retinaldehyde and retinol as a consequence of 4-oxo derivatization suggests that this metabolic step could serve a critical regulatory function during embryogenesis.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.93.10.4873</identifier><identifier>PMID: 8643496</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Absorption spectra ; Agonists ; Animals ; Binding, Competitive ; Biochemistry ; Cell Line ; Cellular biology ; Embryos ; Female ; Freshwater ; Hormones ; Ligands ; Parasites ; Photodiodes ; Receptors ; Receptors, Retinoic Acid - genetics ; Receptors, Retinoic Acid - metabolism ; Retinaldehyde - analogs & derivatives ; Retinaldehyde - metabolism ; Retinoid X Receptors ; Retinoids ; Retinoids - chemistry ; Retinoids - metabolism ; Solvents ; Transcription Factors - metabolism ; Transfection ; Tretinoin - analogs & derivatives ; Tretinoin - metabolism ; Vitamin A - analogs & derivatives ; Vitamin A - metabolism ; Xenopus ; Xenopus - embryology ; Xenopus - genetics ; Xenopus - metabolism</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1996-05, Vol.93 (10), p.4873-4878</ispartof><rights>Copyright 1996 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences May 14, 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-2c7a4479fb1e547ef14390ba250186c6b3242ff16c4bf5f5ffe91478211f8d883</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/93/10.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/38869$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/38869$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8643496$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Blumberg, Bruce</creatorcontrib><creatorcontrib>Bolado, Jack</creatorcontrib><creatorcontrib>Derguini, Fadila</creatorcontrib><creatorcontrib>Craig, A. Grey</creatorcontrib><creatorcontrib>Moreno, Tanya A.</creatorcontrib><creatorcontrib>Chakravarti, Debabrata</creatorcontrib><creatorcontrib>Heyman, Richard A.</creatorcontrib><creatorcontrib>Buck, Jochen</creatorcontrib><creatorcontrib>Evans, Ronald M.</creatorcontrib><title>Novel Retinoic Acid Receptor Ligands in Xenopus Embryos</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Retinoids are a large family of natural and synthetic compounds related to vitamin A that have pleiotropic effects on body physiology, reproduction, immunity, and embryonic development. The diverse activities of retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the RARs and RXRs. Retinoic acids are thought to be the only natural ligands for these receptors and are widely assumed to be the active principle of vitamin A. However, during an unbiased, bioactivity-guided fractionation of Xenopus embryos, we were unable to detect significant levels of all-trans or 9-cis retinoic acids. Instead, we found that the major bioactive retinoid in the Xenopus egg and early embryo is 4-oxoretinaldehyde, which is capable of binding to and transactivating RARs. In addition to its inherent activity, 4-oxoretinaldehyde appears to be a metabolic precursor of two other RAR ligands, 4-oxoretinoic acid and 4-oxoretinol. The remarkable increase in activity of retinaldehyde and retinol as a consequence of 4-oxo derivatization suggests that this metabolic step could serve a critical regulatory function during embryogenesis.</description><subject>Absorption spectra</subject><subject>Agonists</subject><subject>Animals</subject><subject>Binding, Competitive</subject><subject>Biochemistry</subject><subject>Cell Line</subject><subject>Cellular biology</subject><subject>Embryos</subject><subject>Female</subject><subject>Freshwater</subject><subject>Hormones</subject><subject>Ligands</subject><subject>Parasites</subject><subject>Photodiodes</subject><subject>Receptors</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Receptors, Retinoic Acid - metabolism</subject><subject>Retinaldehyde - analogs & derivatives</subject><subject>Retinaldehyde - metabolism</subject><subject>Retinoid X Receptors</subject><subject>Retinoids</subject><subject>Retinoids - chemistry</subject><subject>Retinoids - metabolism</subject><subject>Solvents</subject><subject>Transcription Factors - metabolism</subject><subject>Transfection</subject><subject>Tretinoin - analogs & derivatives</subject><subject>Tretinoin - metabolism</subject><subject>Vitamin A - analogs & derivatives</subject><subject>Vitamin A - metabolism</subject><subject>Xenopus</subject><subject>Xenopus - embryology</subject><subject>Xenopus - genetics</subject><subject>Xenopus - metabolism</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFrFDEYxYModVs9C4Iy9KCn2eZLMpMEvJRSq7AoiIK3kMkmNctsMiYzpf3vm2HXrXpQcgiP93sfX_IQegF4CZjTsyHovJS0iCUTnD5CC8AS6pZJ_BgtMCa8Foywp-g45w3GWDYCH6Ej0TLKZLtA_FO8sX31xY4-RG-qc-PXRRk7jDFVK3-twzpXPlTfbYjDlKvLbZfuYn6GnjjdZ_t8f5-gb-8vv158qFefrz5enK9q04AYa2K4ZoxL14FtGLcOGJW406TBIFrTdpQw4hy0hnWuKcdZCYwLAuDEWgh6gt7t5g5Tt7VrY8OYdK-G5Lc63amovfrTCf6Huo43ikrKSYm_2cdT_DnZPKqtz8b2vQ42TllxgQEAN_8FoWk4A94W8PQvcBOnFMofKIKBCCpAFuhsB5kUc07WHRYGrObe1NybknTWc28l8er3dx74fVHFf7v35-Av92GAclPfj_Z2LOTrf5IFeLkDNrl0fCCoEK2k95M2s-0</recordid><startdate>19960514</startdate><enddate>19960514</enddate><creator>Blumberg, Bruce</creator><creator>Bolado, Jack</creator><creator>Derguini, Fadila</creator><creator>Craig, A. Grey</creator><creator>Moreno, Tanya A.</creator><creator>Chakravarti, Debabrata</creator><creator>Heyman, Richard A.</creator><creator>Buck, Jochen</creator><creator>Evans, Ronald M.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>F1W</scope><scope>H95</scope><scope>L.G</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960514</creationdate><title>Novel Retinoic Acid Receptor Ligands in Xenopus Embryos</title><author>Blumberg, Bruce ; Bolado, Jack ; Derguini, Fadila ; Craig, A. 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Grey</au><au>Moreno, Tanya A.</au><au>Chakravarti, Debabrata</au><au>Heyman, Richard A.</au><au>Buck, Jochen</au><au>Evans, Ronald M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Retinoic Acid Receptor Ligands in Xenopus Embryos</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1996-05-14</date><risdate>1996</risdate><volume>93</volume><issue>10</issue><spage>4873</spage><epage>4878</epage><pages>4873-4878</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Retinoids are a large family of natural and synthetic compounds related to vitamin A that have pleiotropic effects on body physiology, reproduction, immunity, and embryonic development. The diverse activities of retinoids are primarily mediated by two families of nuclear retinoic acid receptors, the RARs and RXRs. Retinoic acids are thought to be the only natural ligands for these receptors and are widely assumed to be the active principle of vitamin A. However, during an unbiased, bioactivity-guided fractionation of Xenopus embryos, we were unable to detect significant levels of all-trans or 9-cis retinoic acids. Instead, we found that the major bioactive retinoid in the Xenopus egg and early embryo is 4-oxoretinaldehyde, which is capable of binding to and transactivating RARs. In addition to its inherent activity, 4-oxoretinaldehyde appears to be a metabolic precursor of two other RAR ligands, 4-oxoretinoic acid and 4-oxoretinol. The remarkable increase in activity of retinaldehyde and retinol as a consequence of 4-oxo derivatization suggests that this metabolic step could serve a critical regulatory function during embryogenesis.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8643496</pmid><doi>10.1073/pnas.93.10.4873</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1996-05, Vol.93 (10), p.4873-4878 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pnas_primary_93_10_4873 |
| source | MEDLINE; Jstor Complete Legacy; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Absorption spectra Agonists Animals Binding, Competitive Biochemistry Cell Line Cellular biology Embryos Female Freshwater Hormones Ligands Parasites Photodiodes Receptors Receptors, Retinoic Acid - genetics Receptors, Retinoic Acid - metabolism Retinaldehyde - analogs & derivatives Retinaldehyde - metabolism Retinoid X Receptors Retinoids Retinoids - chemistry Retinoids - metabolism Solvents Transcription Factors - metabolism Transfection Tretinoin - analogs & derivatives Tretinoin - metabolism Vitamin A - analogs & derivatives Vitamin A - metabolism Xenopus Xenopus - embryology Xenopus - genetics Xenopus - metabolism |
| title | Novel Retinoic Acid Receptor Ligands in Xenopus Embryos |
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