title: Reconstitution of HuR-Inhibited CUGBP1 Expression Protects Cardiomyocytes from Acute Myocardial Infarction-Induced Injury.
abstract: OBJECTIVE
  Myocardial infarction (MI) is one of the leading causes of death in elderly people. Expanding the knowledge of the molecular mechanisms underlying MI is of profound importance to developing a cure for MI. The CUGBP- and ETR-3-like factor (CELF) proteins, a family of RNA-binding proteins, play key roles in RNA metabolism. To determine the functions and molecular mechanisms of CELF proteins in MI, an animal model of acute myocardial infarction (AMI) was used in our study.
  
  
  RESULTS
  We found that the CUG triplet repeat RNA-binding protein 1 (CUGBP1)/CELF1 expression levels were decreased in AMI-injured hearts, and further studies showed that two highly conserved adenylate-uridylate-rich (AU-rich) elements in the 3'UTR of CUGBP1 were responsible for the decreased CUGBP1 expression. Upon AMI, human antigen R (HuR) was relocated to the cytoplasm from the nucleus and interacted with these AU-rich elements to affect the expression of CUGBP1. Reintroduction of CUGBP1 via gene delivery by recombinant adenovirus improved cardiac function in AMI mice. Our studies also indicated that CUGBP1 protected cardiomyocytes from ischemia-induced injury through the promotion of angiogenesis and inhibition of apoptosis by regulating the vascular endothelial growth factor-A gene. Innovation and Conclusion: Our studies indicate a role for CUGBP1 in cardiac disease and reveal a novel MI post-transcriptional gene regulatory mechanism. The reconstitution of CUGBP1 could be developed as a potential therapeutic option for the management of MI. Antioxid. Redox Signal. 27, 1013-1026.
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 University of the Chinese Academy of Sciences , Beijing, China .
authors.forename: Lei
authors.initials: L
authors.lastname: Gu
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .
authors.forename: Huiwen
authors.initials: H
authors.lastname: Wang
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 University of the Chinese Academy of Sciences , Beijing, China .
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 University of the Chinese Academy of Sciences , Beijing, China .
authors.forename: Yuting
authors.initials: Y
authors.lastname: Guo
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .
authors.forename: Yinglong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .|2 University of the Chinese Academy of Sciences , Beijing, China .
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: 3 Beijing Institutes of Life Science , Chinese Academy of Sciences, Beijing, China .
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
authors.affiliation: 4 Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University , Cleveland, Ohio.
authors.forename: Hua
authors.initials: H
authors.lastname: Lou
authors.affiliation: 1 National Laboratory of Biomacromolecules, Institute of Biophysics , Chinese Academy of Sciences, Beijing, China .
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000067879:CELF1 Protein / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000067879:CELF1 Protein; C502743:CELF1 protein, mouse; D000067780:ELAV-Like Protein 1; C000593997:Elavl1 protein, mouse
keywords: CUGBP1; HuR; RNA-binding protein; VEGF-A; hypoxia; myocardial infarction