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

Xue-Liang Zhou1, Xia Wu1, Rong-Rong Zhu2

  • 1Department of Cardiac Surgery, The First Affiliated Hospital, Nanchang University, Nanchang, China.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|February 19, 2020
PubMed

Insights

Notch1 and Keap1-Nrf2 pathway crosstalk protects heart cells from injury. This interaction reduces harmful reactive oxygen species, improving survival and antioxidant capacity in myocardial ischemia-reperfusion injury.

Area of Science:

  • Cardiovascular Biology
  • Cellular Signaling
  • Oxidative Stress Research

Background:

  • Notch1 and Keap1-Nrf2 pathways offer cardioprotection.
  • The role of their crosstalk in myocardial ischemia-reperfusion injury (MIRI) remains largely unknown.

Purpose of the Study:

  • To investigate the protective effects of Notch1-Nrf2 pathway crosstalk in a rat model of MIRI.
  • To elucidate the mechanisms underlying this protection, focusing on oxidative stress.

Main Methods:

  • Utilized a hypoxia-reoxygenation model in neonatal rat cardiomyocytes.
  • Employed a gamma-secretase inhibitor to block Notch1 and curcumin to activate Keap1-Nrf2.
  • Assessed cardiomyocyte viability, apoptosis, reactive oxygen species (ROS) generation, and antioxidant activity.

Main Results:

  • Combined activation of Notch1 and Keap1-Nrf2 pathways significantly enhanced cardiomyocyte viability.
  • The crosstalk notably inhibited cardiomyocyte apoptosis and reduced ROS formation.
  • Increased antioxidant activities were observed in cardiomyocytes treated with combined pathway modulators.

Conclusions:

  • Notch1-Nrf2 pathway crosstalk demonstrates significant cardioprotective effects against MIRI.
  • This protection is mediated, at least in part, by the reduction of reactive oxygen species.
  • Targeting Notch1-Nrf2 crosstalk represents a potential therapeutic strategy for MIRI.
Keywords:
DROKeap1Notch1 signalingNrf2ROSmyocardial protectionprotection du myocardesignalisation Notch1

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