Notch1-Nrf2 signaling crosstalk provides myocardial protection by reducing ROS formation

Biochem Cell Biol. 2020 Apr;98(2):106-111. doi: 10.1139/bcb-2018-0398. Epub 2020 Feb 18.

Abstract

Both the Notch1 and Keap1-Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1-Nrf2 crosstalk in myocardial ischemia-reperfusion injury is unclear. In this study, we established hypoxia-reoxygenation in neonate rat myocardial cells and employed γ-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1-Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1-Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1-Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species.

Keywords: DRO; Keap1; Notch1 signaling; Nrf2; ROS; myocardial protection; protection du myocarde; signalisation Notch1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antioxidants / metabolism
  • Apoptosis
  • Cell Hypoxia
  • Cell Nucleus / metabolism
  • Cell Proliferation
  • Cell Survival
  • Cytoplasm / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hypoxia
  • Kelch-Like ECH-Associated Protein 1 / metabolism*
  • Myocardial Ischemia / metabolism*
  • Myocardial Reperfusion Injury / metabolism*
  • Myocardium / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Receptor, Notch1 / metabolism*
  • Signal Transduction

Substances

  • Antioxidants
  • KEAP1 protein, rat
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Notch1 protein, rat
  • Reactive Oxygen Species
  • Receptor, Notch1