Constitutive NF-kappa B activity in neurons

Mol Cell Biol. 1994 Jun;14(6):3981-92. doi: 10.1128/mcb.14.6.3981-3992.1994.

Abstract

NF-kappa B is inducible transcription factor present in many cell types in a latent cytoplasmic form. So far, only immune cells including mature B cells, thymocytes, and adherent macrophages have been reported to contain constitutively active forms of NF-kappa B in the nucleus. A recent study showed that the human immunodeficiency virus type 1 (HIV-1) promoter is highly active in several brain regions of transgenic mice (J. R. Corboy, J. M. Buzy, M. C. Zink, and J. E. Clements, Science 258:1804-1807, 1992). Since the activity of this viral enhancer is governed mainly by two binding sites for NF-kappa B, we were prompted to investigate the state of NF-kappa B activity in neurons. Primary neuronal cultures derived from rat hippocampus and cerebral cortex showed a high constitutive expression of an HIV-1 long terminal repeat-driven luciferase reporter gene, which was primarily dependent on intact NF-kappa B binding sites and was abolished upon coexpression of the NF-kappa B-specific inhibitor I kappa B-alpha. Indirect immunofluorescence and confocal laser microscopy showed that the activity of NF-kappa B correlated with the presence of the NF-kappa B subunits p50 and RelA (p65) in nuclei of cultured neurons. NF-kappa B was also constitutively active in neurons in vivo. As investigated by electrophoretic mobility shift assays, constitutive NF-kappa B DNA-binding activity was highly enriched in fractions containing neuronal nuclei prepared from rat cerebral cortex. Nuclear NF-kappa B-specific immunostaining was also seen in cryosections from mouse cerebral cortex and hippocampus. Only a subset of neurons was stained. Activated NF-kappa B in the brain is likely to participate in normal brain function and to reflect a distinct state of neuronal activity or differentiation. Furthermore, it may explain the high level of activity of the HIV-1 enhancer in neurons, an observation potentially relevant for the etiology of the AIDS dementia complex caused by HIV infection of the central nervous system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cells, Cultured
  • Cerebral Cortex / metabolism*
  • Fluorescent Antibody Technique
  • HIV Long Terminal Repeat
  • HIV-1 / genetics
  • HeLa Cells
  • Hippocampus / metabolism*
  • Humans
  • Luciferases / biosynthesis
  • Luciferases / metabolism
  • NF-kappa B / analysis
  • NF-kappa B / biosynthesis
  • NF-kappa B / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Rats
  • Rats, Wistar
  • Transcription Factor RelA
  • Transcription, Genetic*
  • Transfection

Substances

  • NF-kappa B
  • Transcription Factor RelA
  • Luciferases