title: Posttranscriptional regulation of the β2-subunit of cardiac L-type Ca2+ channels by MicroRNAs during long-term exposure to isoproterenol in rats.
abstract: METHODS
  The effects of long-term β-adrenergic administration on the expression levels of the cardiac L-type Ca channel β2 subunit, which regulates channel trafficking and function, were characterized in adult rats.
  
  
  RESULTS
  Systemic administration of isoproterenol (150 mg·kg·h) for 2 d led to a 50% increase in the ventricular wet weight-to-body weight ratio (mg/g) and of more than two-fold in the expression of actin protein. In contrast, β2 subunit protein levels decreased (down to 49%), while mRNA levels remained unchanged. Furthermore, levels of microRNAs (miRs), including miR-21 and miR-132, were upregulated (7.2 and 7.9 fold, respectively). Transfection of these miRs into HEK293 cells attenuated expression of a luciferase reporter gene controlled by a conserved 3'-untranslated region (UTR) of the β2 subunit (down to 67% and 56%, respectively). Systemic administration of isoproterenol also led to briefer intracellular Ca transients during action potentials measured in isolated cardiomyocytes (down to 65%).
  
  
  CONCLUSIONS
  These results suggest that cardiac L-type Ca channel β2 subunit protein expression may be downregulated by miRs in response to long-term activation of β-adrenergic signaling, possibly as an adaptive response in cardiac hypertrophy and sustained β-adrenergic states.
authors.affiliation: Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados, del Instituto Politécnico Nacional, México, DF, México.
authors.forename: Elba D
authors.initials: ED
authors.lastname: Carrillo
authors.forename: Yesenia
authors.initials: Y
authors.lastname: Escobar
authors.forename: German
authors.initials: G
authors.lastname: González
authors.forename: Ascención
authors.initials: A
authors.lastname: Hernández
authors.forename: José M
authors.initials: JM
authors.lastname: Galindo
authors.forename: María C
authors.initials: MC
authors.lastname: García
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Sánchez
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000199:Actins / Q000378:metabolism; D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D051242:Caveolin 1 / Q000378:metabolism; D051243:Caveolin 2 / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D057809:HEK293 Cells; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D000199:Actins; C491527:Cacnb2 protein, rat; D020746:Calcium Channels, L-Type; C495537:Cav1 protein, rat; C495546:Cav2 protein, rat; D051242:Caveolin 1; D051243:Caveolin 2; C548821:MIRN132 microRNA, rat; C568897:MIRN222 microRNA, rat; C570112:MIRN31 microRNA, rat; D035683:MicroRNAs; C559947:Mirn214 microRNA, rat; D020033:Protein Isoforms; C546082:mirn21 microRNA, rat; D007545:Isoproterenol