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PMID: 8196637 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Constitutive NF-kappa B activity in neurons.

Molecular and cellular biology ·Vol. 14 ·No. 6 ·1994-06-00 ·Pages 3981-92

Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H, Baeuerle PA

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.

MeSH Terms
Animals Cell Nucleus/metabolism,ultrastructure Cells, Cultured Cerebral Cortex/metabolism Fluorescent Antibody Technique HIV Long Terminal Repeat HIV-1/genetics HeLa Cells Hippocampus/metabolism Humans Luciferases/biosynthesis,metabolism NF-kappa B/analysis,biosynthesis,metabolism Neurons/cytology,metabolism Rats Rats, Wistar Transcription Factor RelA Transcription, Genetic Transfection
Chemicals
NF-kappa B Transcription Factor RelA Luciferases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kaltschmidt C
Institute of Biochemistry, Albert-Ludwigs-Universität, Freiburg, Germany.
Kaltschmidt B
Neumann H
Wekerle H
Baeuerle P A
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.14.6.3981-3992.1994
Published
1994-06-00
Pages
3981-92
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358764
Subset
IM
External Links
PubMed source DOI: 10.1128/mcb.14.6.3981-3992.1994 PMC Full Text View journal details
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