Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adipocytes / metabolism*
-
Adipose Tissue, Brown / embryology
-
Adipose Tissue, Brown / metabolism*
-
Animals
-
Apoptosis
-
Blotting, Northern
-
Blotting, Western
-
CCAAT-Enhancer-Binding Protein-alpha / metabolism
-
CCAAT-Enhancer-Binding Protein-beta / metabolism
-
Carrier Proteins / biosynthesis*
-
Cell Differentiation
-
Cell Nucleus / metabolism
-
Cells, Cultured
-
Enzyme Inhibitors / pharmacology
-
Flavonoids / pharmacology
-
Imidazoles / pharmacology
-
Insulin-Like Growth Factor I / metabolism
-
Intracellular Signaling Peptides and Proteins
-
Ion Channels
-
Membrane Proteins / biosynthesis*
-
Mitochondrial Proteins
-
Mitogen-Activated Protein Kinase Kinases / metabolism
-
Mitogen-Activated Protein Kinases / metabolism*
-
Protein Binding
-
Protein Serine-Threonine Kinases / metabolism
-
Pyridines / pharmacology
-
RNA / metabolism
-
Rats
-
Transcription Factors / metabolism
-
Tumor Necrosis Factor-alpha / pharmacology*
-
Uncoupling Protein 1
-
p38 Mitogen-Activated Protein Kinases
Substances
-
CCAAT-Enhancer-Binding Protein-alpha
-
CCAAT-Enhancer-Binding Protein-beta
-
Carrier Proteins
-
Enzyme Inhibitors
-
Flavonoids
-
Imidazoles
-
Intracellular Signaling Peptides and Proteins
-
Ion Channels
-
Membrane Proteins
-
Mitochondrial Proteins
-
Pyridines
-
Transcription Factors
-
Tumor Necrosis Factor-alpha
-
Ucp1 protein, rat
-
Uncoupling Protein 1
-
RNA
-
Insulin-Like Growth Factor I
-
MAP-kinase-activated kinase 2
-
Protein Serine-Threonine Kinases
-
Mitogen-Activated Protein Kinases
-
p38 Mitogen-Activated Protein Kinases
-
Mitogen-Activated Protein Kinase Kinases
-
SB 203580
-
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one