Abstract / Notes
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.
NF-kappa B/analysis/biosynthesis/*metabolism ; Luciferases/biosynthesis/metabolism ; Humans ; Hippocampus/*metabolism ; Hela Cells ; HIV-1/genetics ; HIV Long Terminal Repeat ; Fluorescent Antibody Technique ; Cerebral Cortex/*metabolism ; Cultured ; Cells ; Animals ; Cell Nucleus/metabolism/ultrastructure ; Neurons/cytology/*metabolism ; Rats ; Rats ; Wistar ; Transcription Factor RelA ; *Transcription ; Genetic ; Transfection
Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H, Baeuerle PA. Constitutive NF-kappa B activity in neurons. Mol Cell Biol. 1994;14(6):3981-92.
Kaltschmidt, C., Kaltschmidt, B., Neumann, H., Wekerle, H., & Baeuerle, P. A. (1994). Constitutive NF-kappa B activity in neurons. Mol Cell Biol, 14(6), 3981-92.
Kaltschmidt, C., Kaltschmidt, B., Neumann, H., Wekerle, H., and Baeuerle, P. A. (1994). Constitutive NF-kappa B activity in neurons. Mol Cell Biol 14, 3981-92.
Kaltschmidt, C., et al., 1994. Constitutive NF-kappa B activity in neurons. Mol Cell Biol, 14(6), p 3981-92.
C. Kaltschmidt, et al., “Constitutive NF-kappa B activity in neurons”, Mol Cell Biol, vol. 14, 1994, pp. 3981-92.
Kaltschmidt, C., Kaltschmidt, B., Neumann, H., Wekerle, H., Baeuerle, P.A.: Constitutive NF-kappa B activity in neurons. Mol Cell Biol. 14, 3981-92 (1994).
Kaltschmidt, Christian, Kaltschmidt, Barbara, Neumann, H., Wekerle, H., and Baeuerle, P. A. “Constitutive NF-kappa B activity in neurons”. Mol Cell Biol 14.6 (1994): 3981-92.
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