Constitutive NF-kappa B activity in neurons

Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H, Baeuerle PA (1994)
Mol Cell Biol 14(6): 3981-92.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
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.
Erscheinungsjahr
Zeitschriftentitel
Mol Cell Biol
Band
14
Zeitschriftennummer
6
Seite
3981-92
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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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