title: ß3-integrin inhibits lipopolysaccharide-induced autophagy in cardiomyocytes via the Akt signaling pathway.
abstract: OBJECTIVE
  To investigate the role of β 3 -integrin in lipopolysaccharide (LPS)-induced autophagy in cardiomyocytes and its underlying mechanism.
  
  
  METHODS
  β 3 -Integrin expression in cardiomyocytes was up- or downregulated by adenovirus transfection or cyclic arginine-glycine-aspartic acid (cRGD) peptide treatment before LPS stimulation. The expression of autophagy-associated proteins (LC3-II, Beclin-1 and Bcl-2) and the activation of Akt were determined using Western blotting. Autophagosomes and autophagic vacuoles were observed using monodansylcadaverine (MDC) dye and transmission electron microscopy, respectively.
  
  
  RESULTS
  Downregulation of β 3 -integrin with cRGD peptide resulted in enhanced LC3-II and Beclin-1 and decreased Bcl-2 expression. Low Beclin-1 levels were detected after LPS stimulation in adenovirus β 3 -integrin-transfected cardiomyocytes. There was no significant difference in LC3-II levels between control and adenovirus β 3 -integrin-transfected cardiomyocytes. Enhanced accumulation of MDC dye and autophagosomes, which were inhibited by β 3 -integrin overexpression, were detected after LPS treatment. The increased phosphorylation of Akt after LPS stimulation was inhibited by cRGD and enhanced by β 3 -integrin overexpression. Furthermore, the Akt inhibitor triciribine inhibited the negative effect of β 3 - integrin on autophagy, as shown by LC3-II and Beclin-1 upregulation.
  
  
  CONCLUSIONS
  β 3 -Integrin inhibits LPS-induced autophagy in cardiomyocytes. The inhibition of Akt signaling might be an important mechanism in this process.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Shijin
authors.initials: S
authors.lastname: Gong
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yu
authors.forename: Haiwen
authors.initials: H
authors.lastname: Dai
authors.forename: Guolong
authors.initials: G
authors.lastname: Cai
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000009:adverse effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D010456:Peptides, Cyclic / Q000627:therapeutic use; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; C491997:BECN1 protein, human; D000071186:Beclin-1; D039661:Integrin beta3; D008070:Lipopolysaccharides; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010456:Peptides, Cyclic; D019253:Proto-Oncogene Proteins c-bcl-2; C507169:cyclic arginine-glycine-aspartic acid peptide; D051057:Proto-Oncogene Proteins c-akt