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M9470047.TXT
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1994-07-02
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Document 0047
DOCN M9470047
TI Constitutive NF-kappa B activity in neurons.
DT 9409
AU Kaltschmidt C; Kaltschmidt B; Neumann H; Wekerle H; Baeuerle PA;
Institute of Biochemistry, Albert-Ludwigs-Universitat, Freiburg,;
Germany.
SO Mol Cell Biol. 1994 Jun;14(6):3981-92. Unique Identifier : AIDSLINE
MED/94254855
AB 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.
DE Animal Cell Nucleus/METABOLISM/ULTRASTRUCTURE Cells, Cultured
Cerebral Cortex/*METABOLISM Comparative Study Fluorescent Antibody
Technique Hela Cells Hippocampus/*METABOLISM Human HIV Long Terminal
Repeat HIV-1/GENETICS Ligases/ANALYSIS/BIOSYNTHESIS
Luciferase/BIOSYNTHESIS/METABOLISM Neurons/CYTOLOGY/*METABOLISM
NF-kappa B/ANALYSIS/*METABOLISM Rats Rats, Wistar Support, Non-U.S.
Gov't *Transcription, Genetic Transfection JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).