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Dose-specific effect of simvastatin on hypoxia-induced HIF-1α and BACE expression in Alzheimer’s disease cybrid cells

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Authors
Jeong, Jin-Heon; Yum, Kyu Sun; Chang, Jun Young; Kim, Manho; Ahn, Jin-young; Kim, SangYun; Lapchak, Paul A; Han, Moon-Ku
Issue Date
2015-07-31
Publisher
BioMed Central
Citation
BMC Neurology, 15(1):127
Keywords
Alzheimer’s diseaseCybrid cellStatinHypoxiaHIF-1αBACE
Description
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium,
provided the original work is properly credited.
Abstract
Abstract

Background
Alzheimer’s disease (AD) is associated with vascular risk factors; brain ischemia facilitates the pathogenesis of AD. Recent studies have suggested that the reduction of AD risk with statin was achieved by decreased amyloidogenic amyloid precursor protein.


Methods
We used mitochondrial transgenic neuronal cell (cybrid) models to investigate changes in the levels of intracellular hypoxia inducible factor 1α (HIF-1α) and β-site amyloid precursor protein cleaving enzyme (BACE) in the presence of simvastatin. Sporadic AD (SAD) and age-matched control (CTL) cybrids were exposed to 2 % O2 and incubated with 1 μM or 10 μM simvastatin.


Results
There was no significant difference between cell survival by 1 or 10 μM simvastatin in both SAD and CTL cybrids. In the presence of 1 μM simvastatin, intracellular levels of HIF-1α and BACE decreased by 40–70 % in SAD, but not CTL cybrids. However, 10 μM simvastatin increased HIF-1α and BACE expression in both cybrid models.


Conclusion
Our results suggest demonstrate differential dose-dependent effects of simvastatin on HIF-1α and BACE in cultured Alzheimer’s disease cybrid cells.
Language
English
URI
http://hdl.handle.net/10371/100552
DOI
https://doi.org/10.1186/s12883-015-0390-5
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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