Aberrant hypermethylation of aldehyde dehydrogenase 2 promoter upstream sequence in rats with experimental myocardial infarction.

Abstract

BACKGROUND:

Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. Downregulation of ALDH2 was evidenced after myocardial infarction and the underlying mechanism is not fully understood. DNA methylation can regulate gene transcription in epigenetic level. We thus hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI).

METHODS:

MI was induced in Sprague-Dawley rats. MI border zone tissues were harvested at 1st week, 2nd week, and 3rd week after MI. Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. Sequenom MassARRAY platform (MassARRAY) was used to examine the methylation levels of ALDH2 promoter upstream sequence. ALDH2 protein and mRNA expression were assayed by Western blot and real-time PCR, respectively.

RESULTS:

Compared with Sham group, ALDH2 protein and mRNA expression of MI groups was significantly downregulated. Compared with Sham group, DNA methylation level of CpG sites in ALDH2 promoter upstream sequence was significantly higher in MI groups in a time-dependent manner (CpG1, CpG2, and CpG7, P < 0.01). DNA methylation did not affect ALDH2 core promoter sequence during the progress of MI. No significant difference was detected in DNA methylation level of ALDH2 promoter upstream sequence among MI groups.

CONCLUSION:

Aberrant hypermethylation of CpG sites in ALDH2 promoter upstream sequence is associated with myocardial ischemia injury and may partly result in ALDH2 downregulation after MI.

• Authors: Peng Wang, Cheng Shen, Lei Diao, Zhiyin Yang, Fan Fan, Cong Wang, Xiangwei Liu, Xiaolei Sun, Zhen Dong, Hong Zhu, Xin Ma, Quan Cao, Xiaona Zhao, Duan Ma, Yunzeng Zou, Kai Hu, Aijun Sun, Junbo Ge
• Journal: BioMed research international (Biomed Res Int) Vol. 2015 Pg. 503692 ( 2015) ISSN: 2314-6141 [Electronic] United States
• PMID: 25629048 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mitochondrial Proteins
• RNA, Messenger
• Transcription Factors
• Decitabine
• Aldehyde Dehydrogenase
• Aldehyde Dehydrogenase, Mitochondrial
• Aldh2 protein, rat
• Azacitidine

Topics

• Aldehyde Dehydrogenase (genetics)
• Aldehyde Dehydrogenase, Mitochondrial
• Animals
• Azacitidine (analogs & derivatives, pharmacology)
• Base Sequence
• Blotting, Western
• CpG Islands (genetics)
• DNA Methylation (drug effects, genetics)
• Decitabine
• Male
• Mitochondrial Proteins (genetics)
• Molecular Sequence Data
• Myocardial Infarction (enzymology, genetics)
• Promoter Regions, Genetic
• RNA, Messenger (genetics, metabolism)
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Reproducibility of Results
• Transcription Factors (metabolism)