TNF-alpha inhibits UCP-1 expression in brown adipocytes via ERKs. Opposite effect of p38MAPK

FEBS Lett. 2001 Mar 23;493(1):6-11. doi: 10.1016/s0014-5793(01)02264-5.

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