NF-κB mediates amyloid β peptide-stimulated activity of the human apolipoprotein E gene promoter in human astroglial cells

摘要: Abstract The apolipoprotein E gene (APOE) plays an important role in the pathogenesis of Alzheimer's disease (AD), and amyloid plaque comprised mostly amyloid-beta peptide (Aβ) is one major hallmarks AD. However, relationship between these two molecules poorly understood. We examined how Aβ treatment affects APOE expression cultured cells tested transcription factor NF-κB regulation. To delineate NF-κB's role, we have characterized a 1098 nucleotide (nt) segment containing 5′-flanking region human (−1054/+44, +1 start site). Sequence analysis this suggests presence potential elements. demonstrate promoter activity, was cloned upstream promoterless luciferase (reporter) gene. This able to drive transient transfections fetal glial cells. Promoter activity stimulated twofold by Aβ1–40 (25 μM, 24 h) treatment. Pretreatment with double-stranded DNA decoy oligonucleotides against (2 μM) reduced stimulation. Deletion mutagenetic analyses demonstrated that distal element functional showed strong DNA–protein complex band gel shift analysis, similar from control consensus element. An anti-inflammatory anti-NF-κB drug, sodium salicylate, significantly blocked Aβ-induced function. Our data provide evidence upregulation astroglial mediated NF-κB-element present