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.
Highlights
Previous study shows aldehyde dehydrogenase 2 (ALDH2) plays a critical role in myocardial protection against ischemia, and down-regulation of Aldehyde dehydrogenase 2 (ALDH2) expression is associated with exacerbated myocardial ischemia injury [1]
Global DNA methylation level and ALDH2 upstream target sequence methylation level were examined with Methylated DNA quantification Kit and MassARRAY, respectively, and expressions of related proteins were determined with Western blot
Our results showed that the baseline methylation levels of all CpG sites in ALDH2 core promoter were at level 0 (Table 4, DNA methylation level standard: level 0 is no methylation, level 1 is 1∼33%, level 2 is 33%∼67%, level 3 is 68%∼99%, and level 4 is 100%) in all 4 examined groups, and the BPS result indicated CpG sites of rat ALDH2 core promoter were not affected by DNA methylation; myocardial infarction (MI) did not trigger the alteration of DNA methylation in ALDH2 core promoter region
Summary
Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. We hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI). Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. 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. 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
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