Document Detail


Rosiglitazone and retinoic acid induce uncoupling protein-1 (UCP-1) in a p38 mitogen-activated protein kinase-dependent manner in fetal primary brown adipocytes.
MedLine Citation:
PMID:  12414803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Brown adipose tissue expresses the thermogenic uncoupling protein-1 (UCP-1), which is positively regulated by peroxisome proliferator-activated receptor (PPAR) agonists and retinoids through the activation of the heterodimers PPAR/retinoid X receptor (RXR) and retinoic acid receptor (RAR)/RXR and binding to specific elements in the ucp-1 enhancer. In this study we show that in fetal rat brown adipocyte primary cultures the PPARgamma agonist rosiglitazone (Rosi), as well as retinoic acids 9-cis-retinoic acid and all-trans-retinoic acid also have "extragenic" effects and induce p44/p42 and p38 mitogen-activated protein kinase (p38MAPK) activation. The latter is involved in UCP-1 gene expression, because inhibition of p38MAPK activity with PD169316 impairs the ability of Rosi and retinoids for UCP-1 induction. The inhibitory effects of PD169316 are mimicked by the antioxidant GSH, suggesting a role for reactive oxygenated species (ROS) generation in the increase of UCP-1 expression in response either to Rosi or 9-cis-retinoic acid. Thus, we propose that Rosi and retinoids act as PPAR/RXR and RAR/RXR agonists and also activate p38MAPK. These two coordinated actions could result in a high increase of transcriptional activity on the ucp-1 enhancer and hence on thermogenesis. PPARalpha and gamma agonists but not retinoids also increase UCP-3 expression in fetal brown adipocytes. However, the regulation of UCP-3, which is not involved in thermogenesis, seems to differ from UCP-1 given the fact that is not affected by p38MAPK inhibition.
Authors:
Teresa Teruel; Rosario Hernandez; Manuel Benito; Margarita Lorenzo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-10-31
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2002-12-30     Completed Date:  2003-02-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  263-9     Citation Subset:  IM    
Affiliation:
Departamento de Bioquimica y Biologia Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / drug effects*,  metabolism
Adipose Tissue, Brown / cytology,  embryology,  metabolism*
Animals
Carrier Proteins / genetics*,  metabolism
Cells, Cultured
Culture Media, Serum-Free
Cyclic AMP / analogs & derivatives,  metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
Enzyme Activation
Enzyme Inhibitors / pharmacology
Fetus
Gene Expression Regulation
Genes, Reporter
Glutathione / pharmacology
Imidazoles / pharmacology
Ion Channels
Membrane Proteins / genetics*,  metabolism
Mitochondrial Proteins
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Promoter Regions, Genetic
Rats
Rats, Wistar
Recombinant Fusion Proteins / genetics,  metabolism
Thiazoles / pharmacology*
Thiazolidinediones*
Tretinoin / chemistry,  pharmacology*
Uncoupling Agents / metabolism*
p38 Mitogen-Activated Protein Kinases
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Culture Media, Serum-Free; 0/Enzyme Inhibitors; 0/Imidazoles; 0/Ion Channels; 0/Membrane Proteins; 0/Mitochondrial Proteins; 0/PD 169316; 0/Recombinant Fusion Proteins; 0/Thiazoles; 0/Thiazolidinediones; 0/Uncoupling Agents; 0/mitochondrial uncoupling protein; 122320-73-4/rosiglitazone; 302-79-4/Tretinoin; 60-92-4/Cyclic AMP; 70-18-8/Glutathione; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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