Abstract
Amyloid-β (Aβ) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by Aβ, is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether Aβ does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Aβ degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether Aβ is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that Aβ reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that Aβ induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in Aβ accumulation, and that Aβ may induce global DNA hypo-methylation.
| Original language | English |
|---|---|
| Pages (from-to) | 57-61 |
| Number of pages | 5 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 378 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2 2009 |
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Keywords
- Alzheimer's disease
- Amyloid-β
- Cerebral amyloid angiopathy
- DNA methylation
- Neprilysin
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Molecular Biology
Cite this
The epigenetic effects of amyloid-β1-40 on global DNA and neprilysin genes in murine cerebral endothelial cells. / Chen, Kun Lin; Wang, Steven Sheng Shih; Yang, Yi Yuan; Yuan, Rey Yue; Chen, Ruei Ming; Hu, Chaur Jong.
In: Biochemical and Biophysical Research Communications, Vol. 378, No. 1, 02.01.2009, p. 57-61.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The epigenetic effects of amyloid-β1-40 on global DNA and neprilysin genes in murine cerebral endothelial cells
AU - Chen, Kun Lin
AU - Wang, Steven Sheng Shih
AU - Yang, Yi Yuan
AU - Yuan, Rey Yue
AU - Chen, Ruei Ming
AU - Hu, Chaur Jong
PY - 2009/1/2
Y1 - 2009/1/2
N2 - Amyloid-β (Aβ) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by Aβ, is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether Aβ does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Aβ degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether Aβ is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that Aβ reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that Aβ induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in Aβ accumulation, and that Aβ may induce global DNA hypo-methylation.
AB - Amyloid-β (Aβ) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by Aβ, is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether Aβ does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for Aβ degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether Aβ is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that Aβ reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that Aβ induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in Aβ accumulation, and that Aβ may induce global DNA hypo-methylation.
KW - Alzheimer's disease
KW - Amyloid-β
KW - Cerebral amyloid angiopathy
KW - DNA methylation
KW - Neprilysin
UR - http://www.scopus.com/inward/record.url?scp=56949102195&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56949102195&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.10.173
DO - 10.1016/j.bbrc.2008.10.173
M3 - Article
C2 - 19007750
AN - SCOPUS:56949102195
VL - 378
SP - 57
EP - 61
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 1
ER -