标题：Aldehyde dehydrogenase 2 protects cardiomyocytes against lipotoxicity via the AKT/glycogen synthase kinase 3 beta pathways
作者：Zhao L.; Fu K.; Li X.; Zhang R.; Wang W.; Xu F.; Ji X.; Chen Y.;等
作者机构：[Zhao, L] Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu 更多
通讯作者地址：[Li, C] Department of Emergency and Chest Pain Center, Qilu Hospital, Shandong University, No. 107, Wenhua Xi Road, Jinan, China;
来源：Biochemical and Biophysical Research Communications
关键词：Aldehyde dehydrogenase 2; Apoptosis; Cardiomyocyte; Lipotoxicity
摘要：Aldehyde dehydrogenase 2, a mitochondrial matrix enzyme, plays a crucial role in protecting the heart against stress, such as ischemia reperfusion and alcohol injury. The present study aimed to investigate the effect of aldehyde dehydrogenase 2 on lipotoxic cardiomyopathy and to explore the possible mechanisms in vitro. Primary cardiomyocytes in the lipotoxic group were treated with oxidatively modified low-density lipoprotein (50 mg/L) for 24 h. Overexpression of aldehyde dehydrogenase 2 was achieved using the aldehyde dehydrogenase 2 activator, Alda-1 (20 μM). We found that cardiomyocyte apoptosis was attenuated by aldehyde dehydrogenase 2 overexpression. In addition, aldehyde dehydrogenase 2 overexpression inhibited the expression of BCL2 associated X, apoptosis regulator (BAX) and caspase 3, while it enhanced protein kinase B (AKT) and glycogen synthase kinase 3 beta (GSK-3β) phosphorylation. The results suggested that aldehyde dehydrogenase 2 is cardioprotective against lipotoxic cardiomyopathy, probably by reducing apoptosis through the AKT/glycogen synthase kinase 3 beta (GSK-3β) pathway. Our findings partially revealed the molecular mechanism of aldehyde dehydrogenase 2’s cardioprotective effect against lipotoxic injury, and suggest a new therapeutic strategy to treat lipotoxic cardiomyopathy. © 2020 Elsevier Inc.