Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180, Feng Lin Road, Shanghai 200032, China.
Biomed Pharmacother. 2011 Dec;65(8):590-3. doi: 10.1016/j.biopha.2009.12.001. Epub 2009 Dec 30.
Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial-specific enzyme, has been proved to be involved in oxidative stress-induced cell apoptosis, while little is known in cardiomyocytes. This study was aimed at investigating the role of ALDH2 in antimycin A-induced cardiomyocytes apoptosis by suppressing ALDH2 activity with a specific ALDH2 inhibitor Daidzin. Antimycin A (40μg/ml) was used to induce neonatal cardiomyocytes apoptosis. Daidzin (60μM) effectively inhibited ALDH2 activity by 50% without own effect on cell apoptosis, and significantly enhanced antimycin A-induced cardiomyocytes apoptosis from 33.5±4.4 to 56.5±6.4% (Hochest method, p<0.05), and from 57.9±1.9 to 74.0±11.9% (FACS, p<0.05). Phosphorylation of activated MAPK signaling pathway, including extracellular signal-regulated kinase (ERK1/2), c-Jun NH2-terminal kinase (JNK) and p38 was also increased in antimycin A and daidzin treated cardiomyocytes compared to the cells treated with antimycin A alone. These findings indicated that modifying mitochondrial ALDH2 activity/expression might be a potential therapeutic option on reducing oxidative insults induced cardiomyocytes apoptosis.
醛脱氢酶 2（ALDH2）是一种线粒体特异性酶，已被证明参与氧化应激诱导的细胞凋亡，而在心肌细胞中知之甚少。本研究旨在通过抑制 ALDH2 活性的特异性 ALDH2 抑制剂大豆苷元来研究 ALDH2 在抗霉素 A 诱导的心肌细胞凋亡中的作用。用 40μg/ml 的抗霉素 A 诱导乳鼠心肌细胞凋亡。大豆苷元（60μM）有效抑制 50%的 ALDH2 活性，而对细胞凋亡无自身作用，并显著增强抗霉素 A 诱导的心肌细胞凋亡，从 33.5±4.4%增加到 56.5±6.4%（Hochest 法，p<0.05），从 57.9±1.9%增加到 74.0±11.9%（FACS，p<0.05）。与单独用抗霉素 A 处理的细胞相比，抗霉素 A 和大豆苷元处理的心肌细胞中激活的 MAPK 信号通路（包括细胞外信号调节激酶（ERK1/2）、c-Jun NH2-末端激酶（JNK）和 p38）的磷酸化也增加。这些发现表明，修饰线粒体 ALDH2 活性/表达可能是减少氧化应激诱导的心肌细胞凋亡的一种潜在治疗选择。
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