Increased expression of microRNA-378a-5p in acute ethanol exposure of rat cardiomyocytes.
Alcohol abuse is a risk factor for a distinct form of congestive heart failure, known as alcoholic cardiomyopathy (ACM). Here, we investigate how microRNAs may participate in the induction of cardiomyocyte apoptosis associated with ethanol exposure in vitro. Increasing the concentrations of ethanol to primary rat cardiomyocytes resulted in elevated apoptosis assessed by annexin V and propidium iodide staining, and reduced expression of an enzyme for alcohol detoxification aldehyde dehydrogenase 2 (ALDH2). These ethanol effects were accompanied by a substantial elevation of miR-378a-5p. Driving miR-378a-5p overexpression in cardiomyocytes decreased ALDH2. The specific interaction of miR-378a-5p with the 3'UTR of ALDH2 was examined by luciferase reporter assays, and we found that miR-378a-5p activity depends on a complementary base pairing at the 3'-UTR region of ALDH2 mRNA. Finally, ethanol-induced apoptosis in cardiomyocytes was attenuated in the presence of anti-miR378a-5p. Collectively, these data implicate a likely involvement of miR-378a-5p in the stimulation of cardiomyocyte apoptosis through ALDH2 gene suppression, which might play a potential role in the pathogenesis of ACM.
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
Zhongkai
Z
Wang
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
Jingwen
J
Song
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
Liang
L
Zhang
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
Songqun
S
Huang
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China.
Lizhi
L
Bao
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China. chenfengshanghai@163.com.
Feng
F
Chen
Department of Cardiovasology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China. zhaoxianxian168@126.com.
Xianxian
X
Zhao
D020413:3' Untranslated Regions; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D017930:Genes, Reporter; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016415:Sequence Alignment; D015854:Up-Regulation / Q000187:drug effects*
D020413:3' Untranslated Regions; D000070416:Antagomirs; D035683:MicroRNAs; D012333:RNA, Messenger; D000431:Ethanol; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat
Alcoholism; Aldehyde dehydrogenase; Apoptosis; Cardiomyocyte; microRNA