Knockdown of p66ShcA activates Nrf2 pathway to protect cardiomyocytes from oxidative stress and inflammation induced by H2O2

Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6994-7001. doi: 10.26355/eurrev_202006_21691.

Abstract

Objective: Oxidative stress and inflammation are the most common causes of myocardial ischemia and hypoxia. This article focuses on the effect of p66ShcA on H2O2-induced cardiomyocytes.

Materials and methods: The p66ShcA knockdown model of H9c2 cells was constructed by plasmid transfection. After treatment of different groups with H2O2, oxidative stress-related factors and inflammatory factors were detected.

Results: The expressions of SOD1, SOD2, GPX1, and GPX3 in H2O2 cells were significantly decreased, IL-1β and IL-6 expression were significantly increased, while p66ShcA siRNA negative group could promote the expression of SOD1, SOD2, GPX1, and GPX3, inhibit the expression of IL-1β and IL-6 significantly, and activates the Keap1/Nrf2 pathways.

Conclusions: Knockdown of p66ShcA can activate Keap1/Nrf2 pathway, which inhibits H2O2-induced oxidative stress and inflammation in H9c2 cells.

MeSH terms

  • Animals
  • Cells, Cultured
  • Hydrogen Peroxide / pharmacology*
  • Inflammation / chemically induced
  • Inflammation / metabolism*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress* / drug effects
  • Rats
  • Src Homology 2 Domain-Containing, Transforming Protein 1 / metabolism*

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, rat
  • Shc1 protein, rat
  • Src Homology 2 Domain-Containing, Transforming Protein 1
  • Hydrogen Peroxide