title: Inhibiting microRNA-144 abates oxidative stress and reduces apoptosis in hearts of streptozotocin-induced diabetic mice.
abstract: BACKGROUND
  Hyperglycemia-induced reactive oxygen species (ROS) generation contributes to the development of diabetic cardiomyopathy. However, little is known about the role of microRNAs in the regulation of ROS formation and myocardial apoptosis in streptozotocin (STZ)-induced diabetic mice.
  
  
  RESULTS
  It was observed that microRNA-144 (miR-144) level was lower in heart tissues of STZ-induced diabetic mice. High glucose exposure also reduced miR-144 levels in cultured cardiomyocytes. Moreover, miR-144 modulated high glucose-induced oxidative stress in cultured cardiomyocytes by directly targeting nuclear factor-erythroid 2-related factor 2 (Nrf2), which was a central regulator of cellular response to oxidative stress. The miR-144 mimics aggravated high glucose-induced ROS formation and apoptosis in cardiomyocytes, which could be attenuated by treatment with Dh404, an activator of Nrf2. Meanwhile, inhibition of miR-144 suppressed ROS formation and apoptosis induced by high glucose in cultured cardiomyocytes. What was more important is that reduced myocardial oxidative stress and apoptosis and improved cardiac function were identified in STZ-induced diabetic mice when treated with miR-144 antagomir.
  
  
  CONCLUSIONS
  Although miR-144 cannot explain the increased oxidative stress in STZ, therapeutic interventions directed at decreasing miR-144 may help to decrease oxidative stress in these hearts. Inhibition of miR-144 might have clinical potential to abate oxidative stress as well as to reduce cardiomyocyte apoptosis and improve cardiac function in diabetic cardiomyopathy.
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bili
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: xianxianz2010@163.com.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005947:Glucose / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009841:Oligonucleotides / Q000008:administration & dosage*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013311:Streptozocin; D014162:Transfection; D016277:Ventricular Function, Left
chemical_list: D020413:3' Untranslated Regions; C551064:MIRN144 microRNA, mouse; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D009841:Oligonucleotides; D017382:Reactive Oxygen Species; D013311:Streptozocin; D005947:Glucose
keywords: Diabetic cardiomyopathy; MicroRNA-144; Nuclear factor-erythroid 2-related factor 2; Oxidative stress; Streptozotocin