Activation of NF-kappa B by reactive oxygen intermediates in the nervous system.
Nuclear factor kappa B (NF-kappa B) is a transcription factor crucially involved in glial and neuronal function. NF-kappa B is ubiquitously distributed within the nervous system, and its inducible activity can be discerned from constitutive activity. Prototypic inducible NF-kappa B in the nervous system is composed of the DNA-binding subunits p50 and p65 complexed with an inhibitory I kappa B-alpha molecule. A number of signals from the cell surface can lead to rapid activation of NK-kappa B, thus releasing the inhibition by I kappa B. This activates translocation of NF-kappa B to the nucleus, where it binds to kappa B motifs of target genes and activates transcription. Previous findings have identified reactive oxygen intermediates (ROI) as a common denominator of NF-kappa B activating signals. More specifically, hydrogen peroxide (H2O2) might be used as second messenger in the NF-kappa B system, despite its cytotoxicity. Analysis of pathways leading to NF-kappa B activation in the nervous system has identified a number of ROI-dependent pathways such as cytokine- and neurotrophin-mediated activation, glutamatergic signal transduction, and various diseases with crucial ROI involvement (e.g., Alzheimer's disease, Parkinson's disease, experimental autoimmune encephalomyelitis, multiple sclerosis, amyotrophic lateral sclerosis, and injury). A number of NF-kappa B-specific target genes contribute to the production of ROI or are involved in detoxification of ROIs. In this review, possible mechanisms and regulatory pathways of ROI-mediated NF-kappa B activation are discussed.
Molecular Neurobiology Laboratory, Albert-Ludwigs-University of Freiburg, D-79104 Freiburg, Germany. kaltschm@uni-freiburg.edu
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Kaltschmidt
D000818:Animals; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism*; D016877:Oxidants / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000502:physiology*
D016328:NF-kappa B; D016877:Oxidants; D017382:Reactive Oxygen Species