The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.
Open accessAbstract
RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways.
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Cites
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
Yung-Chi, C., & Prusoff, W. H. (1973) · Biochemical Pharmacology · doi:10.1016/0006-2952(73)90196-2 · Cited by 12,922
A human retinoic acid receptor which belongs to the family of nuclear receptors
Petkovich, M., Brand, N. J., Krust, A., & Chambon, P. (1987) · Nature · doi:10.1038/330444a0 · Cited by 2,214
Identification of a receptor for the morphogen retinoic acid
Giguere, V., Ong, E. S., Segui, P., & Evans, R. M. (1987) · Nature · doi:10.1038/330624a0 · Cited by 1,965
9-cis retinoic acid is a high affinity ligand for the retinoid X receptor
Heyman, R. A., Mangelsdorf, D. J., Dyck, J. A., Stein, R. B., Eichele, G., Evans, R. M., & Thaller, C. (1992) · Cell · doi:10.1016/0092-8674(92)90479-v · Cited by 1,780 · cited 7×
“Although 9cRA binds and activates RXR with high affinity and potency (Heyman et al., 1992; Levin et al., 1992), the fractions corresponding to this absorbance peak were not tested for RXR activation.”
BackgroundMethodInfluentialSelf-citation
Cited by
Modulation of RXR function through ligand design
Pérez, E., Bourguet, W., Gronemeyer, H., & de Lera, A. R. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.04.003 · Cited by 169
Peroxisomes, lipid metabolism and lipotoxicity
Wanders, R. J. A., Ferdinandusse, S., Brites, P., & Kemp, S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.01.001 · Cited by 169
PEX11β Deficiency Is Lethal and Impairs Neuronal Migration but Does Not Abrogate Peroxisome Function
Li, X., Baumgart, E., Morrell, J. C., Jimenez-Sanchez, G., Valle, D., & Gould, S. J. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.12.4358-4365.2002 · Cited by 165
Brites, P. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg236 · Cited by 116
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Metadata
- Authors
- Kitareewan, S., Burka, L. T., Tomer, K. B., Parker, C. E., Deterding, L. J., Stevens, R. D., Forman, B. M., Mais, D. E., Heyman, R. A., McMorris, T., & Weinberger, C.
- Venue
- Molecular Biology of the Cell
- Published
- 1996-08
- Volume
- 7
- Issue
- 8
- Pages
- 1153-1166
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W1974161676
- Cited by
- 203
- References
- 5
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Kitareewan, S., Burka, L. T., Tomer, K. B., Parker, C. E., Deterding, L. J., Stevens, R. D., Forman, B. M., Mais, D. E., Heyman, R. A., McMorris, T., & Weinberger, C. (1996). Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.7.8.1153
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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