Rosiglitazone and Retinoic Acid Induce Uncoupling Protein-1 (UCP-1) in a p38 Mitogen-activated Protein Kinase-dependent Manner in Fetal Primary Brown Adipocytes
| Autor: | Rosario Lunar Hernández, Teresa Teruel, Margarita Lorenzo, Manuel Benito |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Retinoic acid
Peroxisome proliferator-activated receptor p38 Mitogen-Activated Protein Kinases Biochemistry Culture Media Serum-Free Ion Channels chemistry.chemical_compound Adipose Tissue Brown Genes Reporter Brown adipose tissue Adipocytes Cyclic AMP Enzyme Inhibitors Promoter Regions Genetic Receptor Cells Cultured Uncoupling Protein 1 Mitogen-Activated Protein Kinase 1 chemistry.chemical_classification Imidazoles Glutathione Thermogenin medicine.anatomical_structure Mitogen-Activated Protein Kinases medicine.medical_specialty Recombinant Fusion Proteins Tretinoin Retinoid X receptor Biology Mitochondrial Proteins Rosiglitazone Fetus Internal medicine medicine Animals Rats Wistar Protein kinase A Molecular Biology Uncoupling Agents Membrane Proteins Cell Biology Cyclic AMP-Dependent Protein Kinases Rats Enzyme Activation Thiazoles Retinoic acid receptor Endocrinology Gene Expression Regulation chemistry Thiazolidinediones Carrier Proteins |
| Zdroj: | Journal of Biological Chemistry. 278:263-269 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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