乙醛脱氢酶2可减少氧化损伤诱导的心肌细胞凋亡

乙醛脱氢酶2 (aldehyde dehydrogenase 2, ALDH2)是线粒体特异性酶,已被证明参与氧化应激诱导的细胞凋亡,而在心肌细胞中的作用知之甚少。本研究旨在通过用特异性ALDH2抑制剂大豆苷抑制ALDH2活性来研究ALDH2在抗霉素A诱导的心肌细胞凋亡中的作用。应用抗霉素A和大豆苷诱导小鼠心肌细胞,然后测定ALDH2酶活性、细胞内活性氧(reactive oxy gen species, ROS)含量和细胞凋亡,应用RT-PCR和蛋白质印迹法(Western blotting)检测ALDH2 m RNA和蛋白表达。结果表明,抗霉素A (40μg/mL)可诱导新生心肌细胞凋亡,而大豆苷(50μmol/L)能有效地抑制ALDH2活性而对细胞凋亡没有影响,并且可显著增强抗霉素A诱导的心肌细胞凋亡(53.72%～71.33%, p<0.05)。与单独用抗霉素A处理的细胞相比,抗霉素A和大豆苷共处理的心肌细胞中活化的丝裂原活化蛋白激酶(mitogen-activated protein kinase, MAPK)信号传导途径(p38-MAPK)的磷酸化也显著增加。本研究初步表明,改变线粒体ALDH2活性可能是减少氧化损伤诱导的心肌细胞凋亡的潜在选择。

Reduce Cardiomyocyte Apoptosis of Oxidative Damage-induced by Aldehyde Dehydrogenase 2

Aldehyde dehydrogenase 2(ALDH2)is a mitochondrial-specific enzyme that has been shown to participate in oxidative stress-induced apoptosis but is poorly understood its role in cardiomyocytes.The purpose of this study was to investigate the role of ALDH2 in antimycin A-induced cardiomyocyte apoptosis by inhibiting ALDH2 activity with a specific ALDH2 inhibitor daidzein.Antimycin A and Daidzein were used to induce mouse cardiomyocytes,then ALDH2 enzyme activity,intracellular ROS content and apoptosis were measured.The expression of ALDH2 mRNA and protein was detected by RT-PCR and Western blotting.The results showed that antimycin A(40 μg/mL)could induced apoptosis in neonatal cardiomyocytes.Daidzin(50 μmol/L)could effectively inhibit the ALDH2 activity without affecting apoptosis,and significantly increased antimycin A-induced cardiomyocyte apoptosis(53.72%~71.33%,p<0.05)as well.The phosphorylation of the activated mitogen-activated protein kinase(MAPK)signaling pathway(p38-MAPK)was also significantly increased in antimycin A and Daidzin co-treated cardiomyocytes compared to cells treated with a ntimycin A alone.This study initially indicated that altering mitochondrial ALDH2 activity might be a potential therapeutic option for reducing oxidative damage-induced cardiomyocyte apoptosis.