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
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
Author(s)
Chu R., Madison L.D., Lin Y., Kopp P., Rao M.S., Jameson J.L., Reddy J.K.
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
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 15:43
Last modification date
31/12/2020 6:26
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