Chemical probes that differentially modulate peroxisome proliferator-activated receptor alpha and BLTR, nuclear and cell surface receptors for leukotriene B(4).

Details

Serval ID
serval:BIB_D414CBF35FDB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Chemical probes that differentially modulate peroxisome proliferator-activated receptor alpha and BLTR, nuclear and cell surface receptors for leukotriene B(4).
Journal
Journal of Biological Chemistry
Author(s)
Devchand P.R., Hihi A.K., Perroud M., Schleuning W.D., Spiegelman B.M., Wahli W.
ISSN
0021-9258[print], 0021-9258[linking]
Publication state
Published
Issued date
1999
Volume
274
Number
33
Pages
23341-23348
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
Peroxisome proliferator-activated receptor alpha (PPARalpha)is a nuclear receptor for various fatty acids, eicosanoids, and hypolipidemic drugs. In the presence of ligand, this transcription factor increases expression of target genes that are primarily associated with lipid homeostasis. We have previously reported PPARalpha as a nuclear receptor of the inflammatory mediator leukotriene B(4) (LTB(4)) and demonstrated an anti-inflammatory function for PPARalpha in vivo (Devchand, P. R., Keller, H., Peters, J. M., Vazquez, M., Gonzalez, F. J., and Wahli, W. (1996) Nature 384, 39-43). LTB(4) also has a cell surface receptor (BLTR) that mediates proinflammatory events, such as chemotaxis and chemokinesis (Yokomizo, T., Izumi, T., Chang, K., Takuwa, Y., and Shimizu, T. (1997) Nature 387, 620-624). In this study, we report on chemical probes that differentially modulate activity of these two LTB(4) receptors. The compounds selected were originally characterized as synthetic BLTR effectors, both agonists and antagonists. Here, we evaluate the compounds as effectors of the three PPAR isotypes (alpha, beta, and gamma) by transient transfection assays and also determine whether the compounds are ligands for these nuclear receptors by coactivator-dependent receptor ligand interaction assay, a semifunctional in vitro assay. Because the compounds are PPARalpha selective, we further analyze their potency in a biological assay for the PPARalpha-mediated activity of lipid accumulation. These chemical probes will prove invaluable in dissecting processes that involve nuclear and cell surface LTB(4) receptors and also aid in drug discovery programs.
Keywords
3T3 Cells, Animals, Bacterial Proteins/drug effects, Bacterial Proteins/metabolism, Hela Cells, Humans, Leukotriene B4/metabolism, Ligands, Mice, Molecular Probes, Receptors, Cell Surface/metabolism, Receptors, Cytoplasmic and Nuclear/agonists, Receptors, Cytoplasmic and Nuclear/metabolism, Trans-Activators/drug effects, Trans-Activators/metabolism, Transcription Factors/agonists, Transcription Factors/metabolism, Transcriptional Activation
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:04
Last modification date
20/08/2019 15:54
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