Protective effect of angiotensin-(1-7) against hyperglycaemia-induced injury in H9c2 cardiomyoblast cells via the PI3K̸Akt signaling pathway

Int J Mol Med. 2018 Mar;41(3):1283-1292. doi: 10.3892/ijmm.2017.3322. Epub 2017 Dec 15.

Abstract

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide mainly generated from cleavage of AngⅠ and AngⅡ, possesses physiological and pharmacological properties, including anti‑inflammatory and antidiabetic properties. Activation of the phosphoinositide 3-kinase and protein kinase B (PI3K̸Akt) signaling pathway has been confirmed to participate in cardioprotection against hyperglycaemia-induced injury. The aim of the present study was to test the hypothesis that Ang-(1-7) protects H9c2 cardiomyoblast cells against high glucose (HG)-induced injury by activating the PI3K̸Akt pathway. To examine this hypothesis, H9c2 cells were treated with 35 mmol/l (mM) glucose (HG) for 24 h to establish a HG-induced cardiomyocyte injury model. The cells were co-treated with 1 µmol/l (µM) Ang-(1-7) and 35 mM glucose. The findings of the present study demonstrated that exposure of H9c2 cells to HG for 24 h markedly induced injury, as evidenced by an increase in the percentage of apoptotic cells, generation of reactive oxygen species and level of inflammatory cytokines, as well as a decline in cell viability and mitochondrial luminosity. These injuries were significantly attenuated by co-treatment of the cells with Ang-(1-7) and HG. In addition, PI3K̸Akt phosphorylation was suppressed by HG treatment, but this effect was abolished when the H9c2 cells were co-treated with Ang-(1-7) and HG. Furthermore, the cardioprotection of Ang-(1-7) against HG-induced injury in H9c2 cardiomyoblasts was highly attenuated in the presence of either D-Ala7-Ang-(1-7) (A-779, an antagonist of the Mas receptor) or LY294002 (an inhibitor of PI3K̸Akt). In conclusion, the present study provided new evidence that Ang-(1-7) protects H9c2 cardiomyoblasts against HG-induced injury by activating the PI3K̸Akt signaling pathway.

MeSH terms

  • Angiotensin I / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Cardiotonic Agents / pharmacology*
  • Caspases / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cytoprotection / drug effects
  • Glucose / toxicity
  • Hyperglycemia / pathology*
  • Inflammation / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / enzymology*
  • Myocytes, Cardiac / pathology*
  • Peptide Fragments / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*

Substances

  • Cardiotonic Agents
  • Peptide Fragments
  • Protein Kinase Inhibitors
  • Reactive Oxygen Species
  • Angiotensin I
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspases
  • angiotensin I (1-7)
  • Glucose