Cardioprotective Effects of Glucagon-like Peptide-1 (9-36) Against Oxidative Injury in H9c2 Cardiomyoblasts: Potential Role of the PI3K/Akt/NOS Pathway

J Cardiovasc Pharmacol. 2022 Jan 1;79(1):e50-e63. doi: 10.1097/FJC.0000000000001159.

Abstract

Glucagon-like peptide (GLP)-1(7-36), a major active form of GLP-1 hormone, is rapidly cleaved by dipeptidyl peptidase-4 to generate a truncated metabolite, GLP-1(9-36) which has a low affinity for GLP-1 receptor (GLP-1R). GLP-1(7-36) has been shown to have protective effects on cardiovascular system through GLP-1R-dependent pathway. Nevertheless, the cardioprotective effects of GLP-1(9-36) have not fully understood. The present study investigated the effects of GLP-1(9-36), including its underlying mechanisms against oxidative stress and apoptosis in H9c2 cells. Here, we reported that GLP-1(9-36) protects H9c2 cardiomyoblasts from hydrogen peroxide (H2O2)-induced oxidative stress by promoting the synthesis of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1. In addition, treatment with GLP-1(9-36) suppressed H2O2-induced apoptosis by attenuating caspase-3 activity and upregulating antiapoptotic proteins, Bcl-2 and Bcl-xL. These protective effects of GLP-1(9-36) are attenuated by blockade of PI3K-mediated Akt phosphorylation and prevention of nitric oxide synthase-induced nitric oxide production. Thus, GLP-1(9-36) represents the potential therapeutic target for prevention of oxidative stress and apoptosis in the heart via PI3K/Akt/nitric oxide synthase signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants* / pharmacology
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis* / drug effects
  • Cardiotoxicity
  • Cell Line
  • Glucagon-Like Peptide 1* / analogs & derivatives
  • Glucagon-Like Peptide 1* / pharmacology
  • Hydrogen Peroxide* / toxicity
  • Myoblasts, Cardiac* / drug effects
  • Myoblasts, Cardiac* / enzymology
  • Myoblasts, Cardiac* / pathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase* / metabolism
  • Oxidative Stress* / drug effects
  • Phosphatidylinositol 3-Kinase* / metabolism
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Rats
  • Signal Transduction

Substances

  • Antioxidants
  • Apoptosis Regulatory Proteins
  • Glucagon-Like Peptide 1
  • Hydrogen Peroxide
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • glucagon-like peptide-1 (9-36)