title: MicroRNA-1 aggravates cardiac oxidative stress by post-transcriptional modification of the antioxidant network.
abstract: Oxidative stress plays an important role in cardiovascular diseases. Studies have shown that miR-1 plays an important role in the regulation of cardiomyocyte apoptosis, which can be the result of oxidative stress. This study was designed to determine whether increased miR-1 levels lead to alterations in the expression of proteins related to oxidative stress, which could contribute to heart dysfunction. We compared cardiac function in wild-type (WT) and miR-1 transgene (miR-1/Tg) C57BL/6 mice (n ≥ 10/group). Echocardiography showed that stroke volume (SV), ejection fraction (EF), and fractional shortening (FS) were significantly decreased in miR-1/Tg mice. Concomitantly, the level of reactive oxygen species (ROS) was elevated in the cardiomyocytes from the miR-1/Tg mice, and activities of lactate dehydrogenase (LDH) and creatinine kinase (CK) in plasma were also increased in the miR-1/Tg mice. All of these changes could be reversed by LNA-anti-miR-1. In the cardiomyocytes of neonatal Wistar rats, overexpression of miR-1 exhibits higher ROS levels and lower resistance to H2O2-induced oxidative stress. We demonstrated that SOD1, Gclc, and G6PD are novel targets of miR-1 for post-transcriptional repression. MicroRNA-1 post-transcriptionally represses the expression of SOD1, Gclc, and G6PD, which is likely to contribute to the increased ROS level and the susceptibility to oxidative stress of the hearts of miR-1 transgenic mice.
authors.affiliation: Department of Pharmacology, Harbin Medical University, Xuefu Rd 194, Harbin, 150081, Heilongjiang, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Hequn
authors.initials: H
authors.lastname: Ren
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Cai
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
authors.forename: Zidong Donna
authors.initials: ZD
authors.lastname: Fu
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Lv
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002478:Cells, Cultured; D004794:Enzyme Repression; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: D000975:Antioxidants; C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D005954:Glucosephosphate Dehydrogenase; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D005721:Glutamate-Cysteine Ligase; C544143:GCLC protein, rat