TNF-alpha inhibits UCP-1 expression in brown adipocytes via ERKs. Opposite effect of p38MAPK.
Tumor necrosis factor-alpha (TNF-alpha) activates extracellular-regulated kinases (ERKs) and p38 mitogen-activated protein kinase (p38MAPK), and inhibits the expression of uncoupling protein-1 (UCP-1) and adipocyte-specific genes in rat fetal brown adipocytes. MEK inhibition with PD98059 abolished the inhibitory effect of TNF-alpha on UCP-1, but not on adipogenic genes. In contrast, inhibition of p38MAPK with SB203580 potentiated the negative effect of TNF-alpha on UCP-1 and adipogenic genes. The inhibitory action of TNF-alpha was partially correlated with changes in C/EBPalpha and beta protein levels and in their DNA binding activity, suggesting a role for these transcription factors. However, other transcription factors might explain the different regulation of UCP-1 and adipogenic genes by ERKs.
Departamento de Bioquímica y Biología Molecular II, Instituto de Bioquímica (Centro Mixto del Consejo Superior de Investigaciones Científicas (C.S.I.C.) y de la Universidad Complutense de Madrid (U.C.M.)), Madrid, Spain.
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Valladares
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Roncero
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Benito
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Porras
D017667:Adipocytes / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000196:embryology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D008565:Membrane Proteins / Q000096:biosynthesis*; D024101:Mitochondrial Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007334:Insulin-Like Growth Factor I; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D012313:RNA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2; C000604373:Ucp1 protein, rat; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one