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Chlamydia Pneumoniae-Infected Astrocytes Alter Their Expression of ADAM10, BACE1, and Presenilin-1 Proteases
Alzheimer's & Dementia
  • Zein Al-Atrache, Philadelphia College of Osteopathic Medicine
  • Ahmad Cader
  • Denah Appelt, Philadelphia College of Osteopathic Medicine
Document Type
Conference Proceeding
Publication Date
7-1-2016
Abstract
Background: Utilizing β-amyloid precursor protein (βAPP) as a substrate, α-, β-, and γ-secretases are responsible for sequential cleavage events leading to the formation of β-amyloid, the classic pathologic hallmark of Alzheimer's Disease. Members of this class of proteases also catalyze the activation of numerous other membrane- localized proteins implicated in cell growth and neuroinflammation such as NOTCH and the Interleukin/TNF-receptor family, respectively. This investigation addresses if an in vitro Chlamydia pneumoniae infection of human astrocytes affects the processing of βAPP through modifying the protein expression of the following βAPP processing proteases: A Disintegrin and Metalloproteinase- 10 (ADAM10), βAPP cleaving enzyme-1 (BACE1), and presenilin- 1 (PSEN1). Methods: Human astrocytoma cells (CCF-STTG1) were infected in vitro with Chlamydia pneumoniae strain AR39 (MOI=1). At 6-72 hours post infection, protein level of β-amyloid, ADAM10, BACE1, and presenilin-1 N-terminal fragment (NTF) relative to uninfected controls were detected by immunofluorescence and quantified by western blot analysis. Results: Cytoplasmic labeling of Aβ1-42 was increased in infected cells relative to that of uninfected cells. Membrane-localized labeling of BACE1 and cytoplasmic labeling of PSEN1 NTF was also enhanced at earlier (6 hrs.) and later (48/72 hrs.) time points post infection relative to that of uninfected astrocytes. Increases in quantified BACE1 and PSEN1, but not ADAM10, followed a similar temporal increase most notable at 48 hrs. post infection. Conclusions: These data indicate that infection of human astrocytes with Chlamydia pneumoniae strain AR39 promotes the processing of βAPP characteristic of Alzheimer's Disease through enhancing BACE1 and PSEN1, but not ADAM10, protein levels. Increases in active secretase protein may coincide with the 24-48 hr. lifecycle of Chlamydial intracellular growth and replication and the consequent astrocytic inflammatory response.
Comments

This article was published in Alzheimer's and Dementia, Volume 12, Issue 7, Page P459.

The published version is available at http://dx.doi.org/10.1016/j.jalz.2016.06.894 .

Copyright © 2016.

Citation Information
Zein Al-Atrache, Ahmad Cader and Denah Appelt. "Chlamydia Pneumoniae-Infected Astrocytes Alter Their Expression of ADAM10, BACE1, and Presenilin-1 Proteases" Alzheimer's & Dementia Vol. 12 Iss. 7 (2016) p. P459
Available at: http://works.bepress.com/denah_appelt/44/