Alzheimer amyloid-beta peptides block the activation of C/EBPbeta and C/EBPdelta in glial cells.
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.
Samuelsson
Malin
M
Department of Neurochemistry, Stockholm University, Svante Arrhenius V. 21A, SE10691 Stockholm, Sweden.
Ramberg
Veronica
V
Iverfeldt
Kerstin
K
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D022763:CCAAT-Enhancer-Binding Protein-alpha; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); C113041:amyloid beta-protein (35-25); D051743:CCAAT-Enhancer-Binding Protein-delta; D004247:DNA