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Aβ-induced Ca(2+) influx regulates Astrocytic BACE1 Expression via Calcineurin/NFAT4 signals.
MedLine Citation:
PMID:  22846573     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The β-site APP cleaving enzyme (BACE1) is required for the production of β-amyloid peptides, which give rise to β-amyloid (Aβ) deposits in the brains of Alzheimer's disease (AD) patients. In brains, BACE1 is primarily expressed by neurons, however BACE1 expression has also been observed in reactive astrocytes in close proximity to β-amyloid plaques in the brains of aged Tg2576 AD model mice. To date, the direct effects of Aβ on BACE1 gene expression in astrocytes is unknown. We found that Aβ42 or Aβ25-35 treatment induced BACE1 expression in primary astrocytes as well as human astrocytoma cell line. Aβ neurotoxicity has been associated with the disruption of intracellular calcium homeostasis both in neurons and in glial cells. Here, we demonstrated that NFAT4, a transcription factor tightly regulated by the calcium/calmodulin-dependent phosphatase, calcineurin, was activated in astrocytes applied with calcium ionophore or Aβ. Aβ-activated NFAT4 proteins were associated with astrocytic BACE1 gene expression via direct interaction with the BACE1 promoter region.
Authors:
Seok Min Jin; Hyun Jin Cho; Yong Woo Kim; Ji Yeon Hwang; Inhee Mook-Jung
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  -     ISSN:  1090-2104     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
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