AP-2β regulates amyloid beta-protein stimulation of apolipoprotein e transcription in astrocytes

Ximena S. Rossello, Urule Igbavboa, Gary A. Weisman, Grace Y. Sun, W. Gibson Wood

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Two key players involved in Alzheimer's disease (AD) are amyloid beta protein (Aβ) and apolipoprotein E (apoE). Aβ increases apoE protein levels in astrocytes which is associated with cholesterol trafficking, neuroinflammatory responses and Aβ clearance. The mechanism for the increase in apoE protein abundance is not understood. Based on different lines of evidence, we propose that the beta-adrenergic receptor (βAR), cAMP and the transcription factor activator protein-2 (AP-2) are contributors to the Aβ-induced increase in apoE abundance. This hypothesis was tested in mouse primary astrocytes and in cells transfected with an apoE promoter fragment with binding sites for AP-2. Aβ(42) induced a time-dependent increase in apoE mRNA and protein levels which were significantly inhibited by βAR antagonists. A novel finding was that Aβ incubation significantly reduced AP-2α levels and significantly increased AP-2β levels in the nuclear fraction. The impact of Aβ-induced translocation of AP-2 into the nucleus was demonstrated in cells expressing AP-2 and incubated with Aβ(42). AP-2 expressing cells had enhanced activation of the apoE promoter region containing AP-2 binding sites in contrast to AP-2 deficient cells. The transcriptional upregulation of apoE expression by Aβ(42) may be a neuroprotective response to Aβ-induced cytotoxicity, consistent with apoE's role in cytoprotection.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalBrain Research
Volume1444
DOIs
StatePublished - Mar 20 2012

Bibliographical note

Funding Information:
This work was supported in part by grants from the National Institutes of Health AG-23524 , AG-18357 and the Department of Veterans Affairs .

Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.

Keywords

  • Activator protein-2
  • Alzheimer's disease
  • Amyloid beta-protein
  • Apolipoprotein E
  • Beta-adrenergic receptor
  • Neuroprotection

Fingerprint Dive into the research topics of 'AP-2β regulates amyloid beta-protein stimulation of apolipoprotein e transcription in astrocytes'. Together they form a unique fingerprint.

Cite this