Salusin-β mediates high glucose-induced endothelial injury via disruption of AMPK signaling pathway

Biochem Biophys Res Commun. 2017 Sep 16;491(2):515-521. doi: 10.1016/j.bbrc.2017.06.126. Epub 2017 Jun 21.


The dysregulated proliferation, migration, apoptosis and angiogenesis of endothelial cells are involved in diabetic endothelial dysfunction. The circulating salusin-β levels were increased in diabetic patients, and salusin-β contributes to diabetic cardiomyopathy in rats. However, the roles of salusin-β in diabetes mellitus-induced endothelial dysfunction are not fully understood. Herein, we demonstrated the increased expressions of salusin-β in human umbilical vein endothelial cells (HUVECs) cultured in HG medium. Exposure of HUVECs to HG inhibited the proliferation, migration, and angiogenesis, retarded cell cycle progression of endothelial cells, which were rescued by knockdown of salusin-β. We also established that silencing of salusin-β with adenoviruse-mediated shRNA reduced high glucose-induced apoptosis by up-regulating Bcl-2 expression and down-regulating Bax and caspase-3 expressions. Blockade of salusin-β ameliorated HG-induced suppression of adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Of note, pretreatment with AMPK inhibitor Compound C abolished salusin-β silencing-mediated endothelial protective effects. In summary, our results highlighted the involvement of salusin-β in HG-related endothelial dysfunction, and salusin-β contributed high glucose-induced endothelial injury via inactivation of AMPK signaling pathway.

Keywords: AMPK; Diabetes; Endothelial cell; Endothelial dysfunction; Salusin.

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / genetics*
  • AMP-Activated Protein Kinases / metabolism
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Cell Cycle / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation
  • Gene Silencing
  • Glucose / toxicity*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • BAX protein, human
  • BCL2 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazoles
  • Pyrimidines
  • RNA, Small Interfering
  • TOR2A protein, human
  • bcl-2-Associated X Protein
  • dorsomorphin
  • AMP-Activated Protein Kinases
  • CASP3 protein, human
  • Caspase 3
  • Glucose