S100B potently activates p65/c-Rel transcriptional complexes in hippocampal neurons: Clinical implications for the role of S100B in excitotoxic brain injury
Abstract
Increased serum levels of S100B are positively correlated with multiple forms of CNS damage, such as stroke, CNS trauma and neurodegenerative diseases, but also in psychiatric disorders. However, it is currently not known whether increased serum levels of S100B reflect a neuroregenerative or neurodegenerative response. Since glutamate receptor overactivation (excitotoxicity) may contribute to neuronal pathology in psychiatric disorders, we investigated the effect of S100B on N-methyl-d-aspartate (NMDA)-induced neuronal cell death. Here we demonstrate that very low concentrations of S100B significantly protect primary rat hippocampal neurons against NMDA toxicity by activation of transcription factors of the Rel/nuclear factor kappaB (NF-kappaB) family. Further experiments suggest that i) S100B activated expression of the receptor of advanced glycation products (RAGE) gene in neurons and ii) S100B induced a unique composition of the active NF-kappaB complex consisting of the p65 and c-Rel subunits suggesting a novel mechanism for NF-kappaB activation involved in S100B-mediated neuroprotection. Our data suggest that S100B secreted during the glial response to brain injury potently activates p65/c-Rel in a RAGE-dependent manner and may exert neuroprotective and neuroregenerative effects in psychiatric disorders.
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No difference was found in the levels of P300, cREL or NFATc in rTg4510 mice.
“No difference was found in the levels of P300, cREL or NFATc (data not shown), transcription factors that have been implicated in different neurodegeneration models (73 -76).”
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- Authors
- Kögel, D., Peters, M., König, H.-G., Hashemi, S. M. A., Bui, N. T., Arolt, V., Rothermundt, M., & Prehn, J. H. M.
- Affiliations
- Goethe University Frankfurt (DE)
- University of Münster (DE)
- Corresponding author
- Kögel, D.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 127
- Issue
- 4
- Pages
- 913-920
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2059693555
- Cited by
- 82
- References
- 33
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 6
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- S100B, NF-κB p65, c-Rel, NF-κB activation, hippocampal neurons, excitotoxicity, neuroprotection, receptor for advanced glycation end products, glial response, nerve regeneration, mental illness, brain injury
- MeSH terms
- Animals, Animals, Newborn, Brain Injuries, Carrier Proteins, Cells, Cultured, Hippocampus, Neoplasm Proteins, Nerve Growth Factors, S100 Proteins, Neurons, Transcription, Genetic, Cell Death, Rats, Wistar, Excitatory Amino Acid Agonists, Proto-Oncogene Proteins c-rel, Nucleocytoplasmic Transport Proteins, Rats, S100 Calcium Binding Protein beta Subunit
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