Fatty acids, eicosanoids, and hypolipidemic agents identified as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay

Molecular Endocrinology
G KreyW Wahli

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors controlling the expression of genes involved in lipid homeostasis. PPARs activate gene transcription in response to a variety of compounds including hypolipidemic drugs as well as natural fatty acids. From the plethora of PPAR activators, Scatchard analysis of receptor-ligand interactions has thus far identified only four ligands. These are the chemotactic agent leukotriene B4 and the hypolipidemic drug Wy 14,643 for the alpha-subtype and a prostaglandin J2 metabolite and synthetic antidiabetic thiazolidinediones for the gamma-subtype. Based on the hypothesis that ligand binding to PPAR would induce interactions of the receptor with transcriptional coactivators, we have developed a novel ligand sensor assay, termed coactivator-dependent receptor ligand assay (CARLA). With CARLA we have screened several natural and synthetic candidate ligands and have identified naturally occurring fatty acids and metabolites as well as hypolipidemic drugs as bona fide ligands of the three PPAR subtypes from Xenopus laevis. Our results suggest that PPARs, by their ability to interact with a number of structurally diverse compounds, have acquired unique ligand-bindi...Continue Reading

Citations

Mar 3, 2010·Journal of Inherited Metabolic Disease·Sander Michel Houten, Ronald J A Wanders
Jul 1, 2010·Journal of the American Chemical Society·Peter S Diez, Glenn C Micalizio
Nov 30, 2011·Journal of Medicinal Chemistry·Vincent M CarrollJohn A Katzenellenbogen
Nov 28, 2013·Nature Communications·Katrin RössgerMartin Fussenegger
Aug 23, 2011·Nature Medicine·Guenter HaemmerleRudolf Zechner
Jan 28, 2009·Nature Structural & Molecular Biology·Toshimasa ItohJohn W R Schwabe
Jun 8, 2001·The Biochemical Journal·J P KehrerJ P Vanden Heuvel
Nov 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Yi LiuJohn Y-J Shyy
Feb 10, 2006·Proceedings of the National Academy of Sciences of the United States of America·Chih-Hao LeeRonald M Evans
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Chih-Hao LeeRonald M Evans
Feb 28, 2003·Proceedings of the National Academy of Sciences of the United States of America·Ouliana ZiouzenkovaJorge Plutzky
Oct 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ramasamy Paulmurugan, Sanjiv S Gambhir
Mar 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Grant D BarishChih-Hao Lee
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Frédéric GachonUeli Schibler
Jul 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·T MeyerB Fournier
Apr 20, 2010·The Journal of Biological Chemistry·Venkata R NaralaRaju C Reddy
Oct 20, 2010·The Journal of Biological Chemistry·Michael Schupp, Mitchell A Lazar
Dec 9, 2008·Antioxidants & Redox Signaling·Milton HamblinY Eugene Chen
May 31, 2008·Metabolic Syndrome and Related Disorders·Michael M Swarbrick, Peter J Havel
Jun 2, 2012·Tissue Engineering. Part C, Methods·Ning LaiKyongbum Lee
Nov 10, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Curtis J OmiecinskiJeffrey M Peters
Jul 19, 2006·Molecular and Cellular Biology·Jiajian LiuStephen R Farmer
Mar 23, 2011·The British Journal of Ophthalmology·Andreas StahlLois E H Smith
Jun 28, 2008·PPAR Research·Keisuke TachibanaTakefumi Doi
Jan 7, 2009·PPAR Research·Jennifer L Hatton, Lisa D Yee
Jul 23, 2008·PPAR Research·Markus P Kummer, Michael T Heneka
Aug 2, 2008·PPAR Research·John J BrightSharmistha Chakraborty
Feb 26, 2010·PPAR Research·Eric R WagnerRex C Haydon

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.