Thyroid hormone (T3) inhibits ciprofibrate-induced transcription of genes encoding beta-oxidation enzymes: cross talk between peroxisome proliferator and T3 signaling pathways.
Details
Serval ID
serval:BIB_39E1ED402E13
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Thyroid hormone (T3) inhibits ciprofibrate-induced transcription of genes encoding beta-oxidation enzymes: cross talk between peroxisome proliferator and T3 signaling pathways.
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
05/12/1995
Peer-reviewed
Oui
Volume
92
Number
25
Pages
11593-11597
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
Publication Status: ppublish
Abstract
Peroxisome proliferators cause rapid and coordinated transcriptional activation of genes encoding peroxisomal beta-oxidation system enzymes by activating peroxisome proliferator-activated receptor (PPAR) isoform(s). Since the thyroid hormone (T3; 3,3',5-triiodothyronine) receptor (TR), another member of the nuclear hormone receptor superfamily, regulates a subset of fatty acid metabolism genes shared with PPAR, we examined the possibility of interplay between peroxisome proliferator and T3 signaling pathways. T3 inhibited ciprofibrate-induced luciferase activity as well as the endogenous peroxisomal beta-oxidation enzymes in transgenic mice carrying a 3.2-kb 5'-flanking region of the rat peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase gene fused to the coding region of luciferase. Transfection assays in hepatoma H4-II-E-C3 and CV-1 cells indicated that this inhibition is mediated by TR in a ligand-dependent fashion. Gel shift assays revealed that modulation of PPAR action by TR occurs through titration of limiting amounts of retinoid X receptor (RXR) required for PPAR activation. Increasing amounts of RXR partially reversed the inhibition in a reciprocal manner; PPAR also inhibited TR activation. Results with heterodimerization-deficient TR and PPAR mutants further confirmed that interaction between PPAR and TR signaling systems is indirect. These results suggest that a convergence of the peroxisome proliferator and T3 signaling pathways occurs through their common interaction with the heterodimeric partner RXR.
Keywords
3-Hydroxyacyl CoA Dehydrogenases/biosynthesis, Animals, Base Sequence, Clofibric Acid/analogs & derivatives, Clofibric Acid/pharmacology, Dose-Response Relationship, Drug, Drug Interactions, Enoyl-CoA Hydratase/biosynthesis, Fibric Acids, Gene Expression Regulation, Enzymologic, Humans, Isomerases/biosynthesis, Mice, Mice, Transgenic, Microbodies/drug effects, Microbodies/enzymology, Microbodies/metabolism, Molecular Sequence Data, Multienzyme Complexes/biosynthesis, Mutation, Oxidation-Reduction, Peroxisomal Bifunctional Enzyme, Protein Binding, Protein Conformation, Rats, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/metabolism, Receptors, Retinoic Acid/genetics, Receptors, Retinoic Acid/metabolism, Receptors, Thyroid Hormone/metabolism, Recombinant Fusion Proteins/biosynthesis, Retinoid X Receptors, Signal Transduction, Transcription Factors/genetics, Transcription Factors/metabolism, Transcription, Genetic, Transcriptional Activation, Triiodothyronine/pharmacology
Pubmed
Web of science
Open Access
Yes
Create date
30/12/2020 16:43
Last modification date
31/12/2020 7:26