| First Author | Rossello XS | Year | 2012 |
| Journal | Brain Res | Volume | 1444 |
| Pages | 87-95 | PubMed ID | 22325097 |
| Mgi Jnum | J:181850 | Mgi Id | MGI:5314278 |
| Doi | 10.1016/j.brainres.2012.01.017 | Citation | Rossello XS, et al. (2012) AP-2beta regulates amyloid beta-protein stimulation of apolipoprotein E transcription in astrocytes. Brain Res 1444:87-95 |
| abstractText | Two key players involved in Alzheimer's disease (AD) are amyloid beta protein (Abeta) and apolipoprotein E (apoE). Abeta increases apoE protein levels in astrocytes which is associated with cholesterol trafficking, neuroinflammatory responses and Abeta 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 (betaAR), cAMP and the transcription factor activator protein-2 (AP-2) are contributors to the Abeta-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. Abeta(42) induced a time-dependent increase in apoE mRNA and protein levels which were significantly inhibited by betaAR antagonists. A novel finding was that Abeta incubation significantly reduced AP-2alpha levels and significantly increased AP-2beta levels in the nuclear fraction. The impact of Abeta-induced translocation of AP-2 into the nucleus was demonstrated in cells expressing AP-2 and incubated with Abeta(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 Abeta(42) may be a neuroprotective response to Abeta-induced cytotoxicity, consistent with apoE's role in cytoprotection. |
