Cox-2 Antagonizes the Protective Effect of Sevoflurane on Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis through Inhibiting the Akt Pathway

Dis Markers. 2021 Dec 7:2021:4114593. doi: 10.1155/2021/4114593. eCollection 2021.

Abstract

Objective: To uncover the protective role of sevoflurane on hypoxia/reoxygenation-induced cardiomyocyte apoptosis through the protein kinase B (Akt) pathway.

Methods: An in vitro hypoxia/reoxygenation (H/R) model was established in cardiomyocyte cell line H9c2. Sevoflurane (SEV) was administrated in H9c2 cells during the reoxygenation period. Viability, layered double hydroxide (LDH) release, and apoptosis in H9c2 cells were determined to assess H/R-induced cell damage. Relative levels of apoptosis-associated genes were examined. Moreover, phosphorylation of Akt was determined.

Results: H/R injury declined viability and enhanced LDH release and apoptotic rate in H9c2 cells. Cyclooxygenase-2 (Cox-2) was upregulated following H/R injury, which was partially reversed by SEV treatment. In addition, SEV treatment reversed changes in viability and LDH release owing to H/R injury in H9c2 cells, which were further aggravated by overexpression of Cox-2. The Akt pathway was inhibited in H9c2 cells overexpressing Cox-2.

Conclusions: Sevoflurane protects cardiomyocyte damage following H/R via the Akt pathway, and its protective effect was abolished by overexpression of Cox-2.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Biomarkers / metabolism
  • Cardiotonic Agents / pharmacology*
  • Cardiotonic Agents / therapeutic use
  • Cell Line
  • Cyclooxygenase 2 / metabolism*
  • Hypoxia / drug therapy*
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Sevoflurane / pharmacology*
  • Sevoflurane / therapeutic use
  • Up-Regulation / drug effects

Substances

  • Biomarkers
  • Cardiotonic Agents
  • Sevoflurane
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Proto-Oncogene Proteins c-akt