Alzheimer amyloid-beta peptides block the activation of C/EBPbeta and C/EBPdelta in glial cells

• Published in: Biochemical and biophysical research communications 2008-06, Vol.370 (4), p.619-622
• Main Authors: Samuelsson, Malin, Ramberg, Veronica, Iverfeldt, Kerstin
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - pharmacology; Animals; CCAAT-Enhancer-Binding Protein-alpha - antagonists & inhibitors; CCAAT-Enhancer-Binding Protein-alpha - metabolism; CCAAT-Enhancer-Binding Protein-delta - antagonists & inhibitors; CCAAT-Enhancer-Binding Protein-delta - metabolism; Cells, Cultured; DNA - metabolism; Interleukin-1beta - pharmacology; Lipopolysaccharides - pharmacology; Neuroglia - drug effects; Neuroglia - metabolism; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Protein Binding - drug effects; Rats; Rats, Sprague-Dawley
• ISSN: 1090-2104
• DOI: 10.1016/j.bbrc.2008.03.150

Members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors have been reported to be up-regulated in Alzheimer's disease. In the present study, we have investigated the effects of amyloid-beta (Abeta) peptides on C/EBPbeta and C/EBPdelta, previously shown to be induced by inflammatory stimuli in glial cells. Surprisingly, electrophoretic mobility shift assay showed that both Abeta(1-42) and Abeta(25-35) blocked C/EBP activation induced by the inflammatory cytokine interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS) in mixed primary glial cell cultures from rat. Abeta also blocked IL-1beta- or LPS-induced C/EBP protein levels. The most prominent effects were observed on DNA binding activity and protein levels of C/EBPdelta. Our results demonstrate a dysregulation of C/EBP when glial cells are activated in the presence of Alzheimer Abeta peptides.