Novel retinoic acid receptor ligands in Xenopus embryos

Bruce Blumberg, Jack Bolado, Fadila Derguini, A. Grey Craig, Tanya A. Moreno, Debabrata Chakravarti, Richard A. Heyman, Jochen Buck, Ronald M. Evans*

*Corresponding author for this work

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91 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4873-4878
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number10
DOIs
StatePublished - May 14 1996

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    Blumberg, B., Bolado, J., Derguini, F., Craig, A. G., Moreno, T. A., Chakravarti, D., Heyman, R. A., Buck, J., & Evans, R. M. (1996). Novel retinoic acid receptor ligands in Xenopus embryos. Proceedings of the National Academy of Sciences of the United States of America, 93(10), 4873-4878. https://doi.org/10.1073/pnas.93.10.4873