Structural requirements and cell-type specificity for ligand activation of peroxisome proliferator-activated receptors

The Journal of Steroid Biochemistry and Molecular Biology
T E JohnsonA Schmidt

Abstract

The mammalian peroxisome proliferator-activated receptor (PPAR) family consists of three different subtypes, PPARalpha, hNUC1/PPARdelta and PPARgamma. Selective agonists have been identified for PPARalpha and PPARgamma but not for hNUC1, and consequently little is known about the genes that are controlled by this receptor. Using ligand-dependent transcription assays in COS-7 cells, we screened a variety of PPAR activating agents to identify a selective activator of hNUC1. We found that the potent peroxisome proliferator, Wy-14643, and the PPARgamma-selective thiazolidinedione, BRL 49653, were poor activators of hNUC1 (EC50s of > 100 microM). Short chain fatty acids (FAs) appeared more selective for PPARalpha than for hNUC1, whereas the very long chain FA, erucic acid (C22:1) was more selective for hNUC1. Using erucic acid as a probe, we conducted a topological similarity search of the Merck Chemical Collection and identified a fatty acid-like compound, L-631,033 4-(2-acetyl-6-hydroxyundecyl) cinnamic acid, that was a selective activator of hNUC1 (EC50 of 2 microM), but was much less selective for PPARalpha or PPARgamma (EC50s of > 100 microM). Structure-function analysis of PPAR activation by L-631,033 structural analogues show...Continue Reading

References

May 16, 1983·Biochimica Et Biophysica Acta·J Norseth, M S Thomassen
Oct 13, 1995·The Journal of Biological Chemistry·K YuM A Lazar
May 15, 1994·Genes & Development·P TontonozB M Spiegelman
Apr 1, 1994·Molecular and Cellular Endocrinology·S Green, W Wahli
Dec 1, 1995·Mutation Research·S Green

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Citations

Jan 27, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D D DiascroA Schmidt
Jan 28, 2012·Expert Opinion on Therapeutic Targets·Laia SalvadóManuel Vázquez-Carrera
Oct 19, 2019·Metabolic Brain Disease·Meric A AltinozEmily Hacker
May 11, 2002·The Proceedings of the Nutrition Society·Miriam N Jacobs, David F V Lewis
Mar 9, 2007·The American Journal of Clinical Nutrition·Eiji Oda
Sep 4, 2010·PPAR Research·Woo Hyung Lee, Sang Geon Kim
Sep 4, 2012·BMC Ophthalmology·Maxwell P Treacy, Tara P Hurst
Aug 24, 1999·Current Opinion in Clinical Nutrition and Metabolic Care·L Gelman, J Auwerx
Oct 26, 1999·Endocrine Reviews·B Desvergne, W Wahli
Jul 25, 2007·Journal of Internal Medicine·W AhmedJ Plutzky
Nov 25, 2018·International Journal of Molecular Sciences·Varsha SheteBayar Thimmapaya
Mar 29, 2014·Journal of Lipid Research·Hidetoshi YamadaKen-Ichi Kimura
Jan 29, 2020·Advanced Drug Delivery Reviews·Jeroen F J BogieJerome J A Hendriks
Dec 26, 2015·Progress in Lipid Research·Philip HallenborgKarsten Kristiansen
Feb 26, 2000·Journal of Medicinal Chemistry·T M WillsonB R Henke
Jun 14, 2005·Biochimica Et Biophysica Acta·Lise MadsenKarsten Kristiansen
Feb 24, 2007·Journal of the American Academy of Dermatology·Mathew M AvramWilliam D James
Jun 17, 2020·Journal of Medicinal Chemistry·Tara Man KadayatJungwook Chin
May 19, 2009·Free Radical Biology & Medicine·Ashlee N HigdonVictor M Darley-Usmar

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