MCP Thermo Scientific TMT Isobaric Mass Tagging Kits
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/mcp.M400003-MCP200 on April 8, 2004.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M400003-MCP200v1
3/7/692    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Glossary
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lengqvist, J.
Right arrow Articles by Griffiths, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lengqvist, J.
Right arrow Articles by Griffiths, W. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Molecular & Cellular Proteomics 3:692-703, 2004.
© 2004 by The American Society for Biochemistry and Molecular Biology, Inc.

Research

Polyunsaturated Fatty Acids Including Docosahexaenoic and Arachidonic Acid Bind to the Retinoid X Receptor {alpha} Ligand-binding Domain*

Johan Lengqvist{ddagger},§, Alexander Mata de Urquiza§, Ann-Charlotte Bergman, Timothy M. Willson||, Jan Sjövall{ddagger}, Thomas Perlmann§ and William J. Griffiths{ddagger},**,{ddagger}{ddagger}

From the {ddagger} Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-17177 Stockholm, Sweden; § Ludwig Institute for Cancer Research, Stockholm Branch, SE-17177 Stockholm, Sweden; Department of Clinical Chemistry, Karolinska Hospital, SE-17177 Stockholm, Sweden; || GlaxoSmithKline, Discovery Research, Research Triangle Park, NC 27709; and ** Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, London WC1N 1AX, United Kingdom

Nuclear receptors (NRs) constitute a large and highly conserved family of ligand-activated transcription factors that regulate diverse biological processes such as development, metabolism, and reproduction. As such, NRs have become important drug targets, and the identification of novel NR ligands is a subject of much interest. The retinoid X receptor (RXR) belongs to a subfamily of NRs that bind vitamin A metabolites (i.e. retinoids), including 9-cis-retinoic acid (9-cis-RA). However, although 9-cis-RA has been described as the natural ligand for RXR, its endogenous occurrence has been difficult to confirm. Recently, evidence was provided for the existence of a different natural RXR ligand in mouse brain, the highly enriched polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) (Mata de Urquiza et al. (2000) Science 290, 2140–2144). However, the results suggested that supra-physiological levels of DHA were required for efficient RXR activation. Using a refined method for ligand addition to transfected cells, the current study shows that DHA is a more potent RXR ligand than previously observed, inducing robust RXR activation already at low micromolar concentrations. Furthermore, it is shown that other naturally occurring PUFAs can activate RXR with similar efficiency as DHA. In additional experiments, the binding of fatty acid ligands to RXR{alpha} is directly demonstrated by electrospray mass spectrometry of the noncovalent complex between the RXR ligand-binding domain (LBD) and its ligands. Data is presented that shows the noncovalent interaction between the RXR LBD and a number of PUFAs including DHA and arachidonic acid, corroborating the results in transfected cells. Taken together, these results show that RXR binds PUFAs in solution and that these compounds induce receptor activation, suggesting that RXR could function as a fatty acid receptor in vivo.

{ddagger}{ddagger} To whom correspondence should be addressed: Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29–39 Brunswick Square, London WC1N 1AX, United Kingdom. Tel.: 44-(0)20-7753-5876; Fax: 44-(0)20-7753-5964; E-mail: william.griffiths{at}ulsop.ac.uk


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
F. Zapata-Gonzalez, F. Rueda, J. Petriz, P. Domingo, F. Villarroya, J. Diaz-Delfin, M. A. de Madariaga, and J. C. Domingo
Human dendritic cell activities are modulated by the omega-3 fatty acid, docosahexaenoic acid, mainly through PPAR{gamma}:RXR heterodimers: comparison with other polyunsaturated fatty acids
J. Leukoc. Biol., October 1, 2008; 84(4): 1172 - 1182.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. M. Nowickyj, J. V. Chithalen, D. Cameron, M. G. Tyshenko, M. Petkovich, G. R. Wyatt, G. Jones, and V. K. Walker
Locust retinoid X receptors: 9-Cis-retinoic acid in embryos from a primitive insect
PNAS, July 15, 2008; 105(28): 9540 - 9545.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
W. L. Huang, V. R. King, O. E. Curran, S. C. Dyall, R. E. Ward, N. Lal, J. V. Priestley, and A. T. Michael-Titus
A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury
Brain, November 1, 2007; 130(11): 3004 - 3019.
[Abstract] [Full Text] [PDF]

Home page
 Protein Sci.Home page
C. Bovet, A. Wortmann, S. Eiler, F. Granger, M. Ruff, B. Gerrits, D. Moras, and R. Zenobi
Estrogen receptor-ligand complexes measured by chip-based nanoelectrospray mass spectrometry: An approach for the screening of endocrine disruptors
Protein Sci., May 1, 2007; 16(5): 938 - 946.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
S. M. Innis
Dietary (n-3) Fatty Acids and Brain Development
J. Nutr., April 1, 2007; 137(4): 855 - 859.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
S. Folkertsma, P. I. van Noort, A. de Heer, P. Carati, R. Brandt, A. Visser, G. Vriend, and J. de Vlieg
The Use of in Vitro Peptide Binding Profiles and in Silico Ligand-Receptor Interaction Profiles to Describe Ligand-Induced Conformations of the Retinoid X Receptor {alpha} Ligand-Binding Domain
Mol. Endocrinol., January 1, 2007; 21(1): 30 - 48.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al.
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors
Pharmacol. Rev., December 1, 2006; 58(4): 798 - 836.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
E. Larque, S. Krauss-Etschmann, C. Campoy, D. Hartl, J. Linde, M. Klingler, H. Demmelmair, A. Cano, A. Gil, B. Bondy, et al.
Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins.
Am. J. Clinical Nutrition, October 1, 2006; 84(4): 853 - 861.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
J.-Z. Zeng, D.-F. Sun, L. Wang, X. Cao, J.-B. Qi, T. Yang, C.-Q. Hu, W. Liu, and X.-K. Zhang
Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha
Carcinogenesis, October 1, 2006; 27(10): 1991 - 2000.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
A. Garelli, N. P. Rotstein, and L. E. Politi
Docosahexaenoic Acid Promotes Photoreceptor Differentiation without Altering Crx Expression.
Invest. Ophthalmol. Vis. Sci., July 1, 2006; 47(7): 3017 - 3027.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
R. J Deckelbaum, T. S Worgall, and T. Seo
n-3 Fatty acids and gene expression
Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1520 - 1525S.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
R. K. Selvaraj and K. C. Klasing
Lutein and Eicosapentaenoic Acid Interact to Modify iNOS mRNA Levels through the PPAR{gamma}/RXR Pathway in Chickens and HD11 Cell Lines
J. Nutr., June 1, 2006; 136(6): 1610 - 1616.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
K. A. R. Tobin, N. K. Harsem, K. T. Dalen, A. C. Staff, H. I. Nebb, and A. K. Duttaroy
Regulation of ADRP expression by long-chain polyunsaturated fatty acids in BeWo cells, a human placental choriocarcinoma cell line
J. Lipid Res., April 1, 2006; 47(4): 815 - 823.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
T. Hashimoto, N. Shimizu, T. Kimura, Y. Takahashi, and T. Ide
Polyunsaturated Fats Attenuate the Dietary Phytol-Induced Increase in Hepatic Fatty Acid Oxidation in Mice
J. Nutr., April 1, 2006; 136(4): 882 - 886.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Ohyama, S. Meaney, M. Heverin, L. Ekstrom, A. Brafman, M. Shafir, U. Andersson, M. Olin, G. Eggertsen, U. Diczfalusy, et al.
Studies on the Transcriptional Regulation of Cholesterol 24-Hydroxylase (CYP46A1): MARKED INSENSITIVITY TOWARD DIFFERENT REGULATORY AXES
J. Biol. Chem., February 17, 2006; 281(7): 3810 - 3820.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.