Amyloid β peptide (Aβ42) activates PLC-δ1 promoter through the NF-κB binding site

The abnormal deposition of amyloid β peptide (Aβ) is a hallmark of Alzheimer's disease (AD). Phospholipase C-δ1 (PLC-δ1) is also known to abnormally accumulate in the brains of AD patients, but no report has addressed the relationship between these two events. This study investigated the effect of Aβ42 on the PLC-δ1 expression in human neuroblastoma cell lines. The PLC-δ1 mRNA level was increased by treatment with Aβ42 in a RT-PCR analysis. In the reporter assay, Aβ42 was found to activate the PLC-δ1 promoter activity in a dose-dependent manner. A novel NF-κB binding site in the PLC-δ1 promoter appeared to be responsible for the Aβ42 activity. First, the dominant negative forms of the NF-κB activating molecules, dominant negative TGF-β activated kinase 1 (dnTAK1) and dnNIK (dominant negative NF-κB-inducing kinase), abolished the Aβ42 activity in the reporter assay. Second, the Aβ42 augmented a factor binding on the NF-κB site in the electrophoretic mobility shift assay (EMSA), which was abolished by a molar excess of the unlabeled consensus NF-κB oligonucleotide. These results suggest that the PLC-δ1 promoter is under the control of NF-κB, which mediates the expression of PLC-δ due to the Aβ42 treatment.