PMID- 11277995 OWN - NLM STAT- MEDLINE DCOM- 20010426 LR - 20220310 IS - 0014-5793 (Print) IS - 0014-5793 (Linking) VI - 493 IP - 1 DP - 2001 Mar 23 TI - TNF-alpha inhibits UCP-1 expression in brown adipocytes via ERKs. Opposite effect of p38MAPK. PG - 6-11 AB - 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. FAU - Valladares, A AU - Valladares A AD - Departamento de Bioquimica y Biologia Molecular II, Instituto de Bioquimica (Centro Mixto del Consejo Superior de Investigaciones Cientificas (C.S.I.C.) y de la Universidad Complutense de Madrid (U.C.M.)), Madrid, Spain. FAU - Roncero, C AU - Roncero C FAU - Benito, M AU - Benito M FAU - Porras, A AU - Porras A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 0 (CCAAT-Enhancer-Binding Protein-beta) RN - 0 (Carrier Proteins) RN - 0 (Enzyme Inhibitors) RN - 0 (Flavonoids) RN - 0 (Imidazoles) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Ion Channels) RN - 0 (Membrane Proteins) RN - 0 (Mitochondrial Proteins) RN - 0 (Pyridines) RN - 0 (Transcription Factors) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Ucp1 protein, rat) RN - 0 (Uncoupling Protein 1) RN - 63231-63-0 (RNA) RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - EC 2.7.1.- (MAP-kinase-activated kinase 2) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) RN - OU13V1EYWQ (SB 203580) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Adipocytes/*metabolism MH - Adipose Tissue, Brown/embryology/*metabolism MH - Animals MH - Apoptosis MH - Blotting, Northern MH - Blotting, Western MH - CCAAT-Enhancer-Binding Protein-alpha/metabolism MH - CCAAT-Enhancer-Binding Protein-beta/metabolism MH - Carrier Proteins/*biosynthesis MH - Cell Differentiation MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - Enzyme Inhibitors/pharmacology MH - Flavonoids/pharmacology MH - Imidazoles/pharmacology MH - Insulin-Like Growth Factor I/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Ion Channels MH - Membrane Proteins/*biosynthesis MH - Mitochondrial Proteins MH - Mitogen-Activated Protein Kinase Kinases/metabolism MH - Mitogen-Activated Protein Kinases/*metabolism MH - Protein Binding MH - Protein Serine-Threonine Kinases/metabolism MH - Pyridines/pharmacology MH - RNA/metabolism MH - Rats MH - Transcription Factors/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Uncoupling Protein 1 MH - p38 Mitogen-Activated Protein Kinases EDAT- 2001/03/30 10:00 MHDA- 2001/05/01 10:01 CRDT- 2001/03/30 10:00 PHST- 2001/03/30 10:00 [pubmed] PHST- 2001/05/01 10:01 [medline] PHST- 2001/03/30 10:00 [entrez] AID - S0014-5793(01)02264-5 [pii] AID - 10.1016/s0014-5793(01)02264-5 [doi] PST - ppublish SO - FEBS Lett. 2001 Mar 23;493(1):6-11. doi: 10.1016/s0014-5793(01)02264-5.