Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha

Biochem Biophys Res Commun. 1995 Nov 13;216(2):568-73. doi: 10.1006/bbrc.1995.2660.

Abstract

A transcription factor NF kappa B, which regulates expression of various cellular genes involved in immune responses and viral genes including HIV, is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B. Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B. Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha, TPA, or H2O2. Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha, indicating that Cu2+ interferes with the dissociation of the NF kappa B-I kappa B complex. Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+. These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / metabolism
  • Copper / pharmacology*
  • Cytoplasm / metabolism
  • DNA-Binding Proteins / antagonists & inhibitors*
  • Enhancer Elements, Genetic
  • Humans
  • Hydrogen Peroxide / pharmacology
  • I-kappa B Proteins*
  • Immunoglobulin kappa-Chains / genetics
  • Kinetics
  • Mice
  • Molecular Sequence Data
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Oligodeoxyribonucleotides
  • Phosphorylation
  • Signal Transduction / drug effects*
  • T-Lymphocytes
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Immunoglobulin kappa-Chains
  • NF-kappa B
  • NFKBIA protein, human
  • Nfkbia protein, mouse
  • Oligodeoxyribonucleotides
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Copper
  • Hydrogen Peroxide
  • Tetradecanoylphorbol Acetate