کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474671 | 1550430 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
β-Blocker carvedilol protects cardiomyocytes against oxidative stress-induced apoptosis by up-regulating miR-133 expression
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کلمات کلیدی
MDAMiR-133GPXDCFH-DA2′,7′-dichlorofluorescin diacetate - 2 '، 7'-dichlorofluorescin diacetateAO/EB - AO / EBROS - ROSMyocardial infarction - آنفارکتوس میوکاردacridine orange/ethidium bromide - آکاردین نارنجی / اتیدیم برومیدOxidative stress - تنش اکسیداتیوApoptosis - خزان یاختهایSOD - سدSuperoxide dismutase - سوکسوکس دیسموتازAMO - عشقmalondialdehyde - مالون دی آلدهیدcarvedilol - کارودیلولCaspase-3 - کاسپاز ۳ Caspase-9 - کاسپاز-9glutathione peroxidase - گلوتاتیون پراکسیدازReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Oxidative stress is a causal factor and key promoter of a variety of cardiovascular diseases associated with apoptotic cell death by causing deregulation of related genes. Though carvedilol, a β-adrenergic blocker, has been shown to produce cytoprotective effects against cardiomyocyte apoptosis, the mechanisms are not fully understood. The present study was designed to investigate whether the beneficial effects of carvedilol are related to microRNAs which have emerged as critical players in cardiovascular pathophysiology via post-transcriptional regulation of protein-coding genes. In vivo, we demonstrated that carvedilol ameliorated impaired cardiac function of infarct rats and restored miR-133 expression. In vitro, carvedilol protected cardiomyocytes from H2O2 induced apoptosis detected by TUNEL staining and MTT assays, and increased miR-133 expression in cardiomyocytes. Overexpression of miR-133, a recognized anti-apoptotic miRNA, produced similar effects to carvedilol: reduction of reactive oxygen species (ROS) and malondialdehyde (MDA) content and increment of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) level, so as to protect cardiomyocytes from apoptosis by downregulating caspase-9 and caspase-3 expression in the presence of H2O2. Transfection with AMO-133 (antisense inhibitor oligodeoxyribonucleotides) alone abolished the beneficial effects of carvedilol. Caspase-9-specific inhibitor z-LEHD-fmk, caspase-3-specific inhibitor z-DEVD-fmk, caspase-9 siRNA and caspase-3 siRNA were used to establish caspase-3 as a downstream target of miR-133. In conclusion, our data indicated that carvedilol protected cardiomyocytes by increasing miR-133 expression and suppressing caspase-9 and subsequent apoptotic pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 75, October 2014, Pages 111-121
Journal: Journal of Molecular and Cellular Cardiology - Volume 75, October 2014, Pages 111-121
نویسندگان
Chaoqian Xu, Yingying Hu, Liangyu Hou, Jin Ju, Xiaoguang Li, Ning Du, Xiaoxiang Guan, Zhenhong Liu, Tianze Zhang, Wei Qin, Nannan Shen, Muhammad U. Bilal, Yanjie Lu, Yong Zhang, Hongli Shan,