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
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