|Rosiglitazone and retinoic acid induce uncoupling protein-1 (UCP-1) in a p38 mitogen-activated protein kinase-dependent manner in fetal primary brown adipocytes.|
|PMID: 12414803 Owner: NLM Status: MEDLINE|
|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.|
|Teresa Teruel; Rosario Hernandez; Manuel Benito; Margarita Lorenzo|
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|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2002-10-31|
|Title: The Journal of biological chemistry Volume: 278 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2003 Jan|
|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|
|Languages: eng Pagination: 263-9 Citation Subset: IM|
|Departamento de Bioquimica y Biologia Molecular II, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.|
|APA/MLA Format Download EndNote Download BibTex|
Adipose Tissue, Brown / cytology, embryology, metabolism*
Carrier Proteins / genetics*, metabolism
Culture Media, Serum-Free
Cyclic AMP / analogs & derivatives, metabolism
Cyclic AMP-Dependent Protein Kinases / metabolism
Enzyme Inhibitors / pharmacology
Gene Expression Regulation
Glutathione / pharmacology
Imidazoles / pharmacology
Membrane Proteins / genetics*, metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinases / antagonists & inhibitors, metabolism*
Promoter Regions, Genetic
Recombinant Fusion Proteins / genetics, metabolism
Thiazoles / pharmacology*
Tretinoin / chemistry, pharmacology*
Uncoupling Agents / metabolism*
p38 Mitogen-Activated Protein Kinases
|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 188.8.131.52/Cyclic AMP-Dependent Protein Kinases; EC 184.108.40.206/Mitogen-Activated Protein Kinase 1; EC 220.127.116.11/Mitogen-Activated Protein Kinases; EC 18.104.22.168/p38 Mitogen-Activated Protein Kinases|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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