Propofol Alleviates DNA Damage Induced by Oxygen Glucose Deprivation and Reperfusion via FoxO1 Nuclear Translocation in H9c2 Cells.

Zejian Wang,Jinqiang Zhuang,Dandan Zhou,Dandan Zhao,Yihui Wang,Lidong Zhao,Jiang Hong,Jinjun Pu,Ming Yin,Shun Zhu,Hongyu Zhang

doi:10.3389/fphys.2019.00223

Abstract

Ischemia/reperfusion (I/R) injury induces irreversible oxidative stress damage to the cardiac myocytes. Many studies have revealed that propofol alleviates the important organelle-mediated injury from oxidative stress in vitro. However, it remains unclear whether propofol prevents I/R-induced DNA damage in cardiomyocytes. In our study, we established an oxygen glucose deprivation/reoxygenation (OGD/R) model in H9c2 cells and found that propofol decreased reactive oxygen species (ROS) levels and suppressed cell apoptosis induced by OGD/R in H9c2 cells. In addition, propofol significantly reduced the molecular marker of DNA damage and inhibited double-strand breaks of DNA damage induced by OGD/R in H9c2 cells in a dose-dependent manner. Furthermore, we investigated the molecular mechanisms and demonstrated that propofol inhibited forkhead box O 1 (FoxO1) phosphorylation and increased FoxO1 nuclear translocation through inhibition of protein kinase B (Akt) and adenosine 5’-monophosphate-activated protein kinase (AMPK) pathways. The protective effects of propofol against oxidative stress-induced DNA damage were reversed by silencing FoxO1. Taken together, our results suggest that oxidative stress aggravates DNA damage and apoptosis in H9C2 cells, which can be reversed by propofol via FoxO1 nuclear translocation.

Highlights

Myocardial ischemia injury followed by reperfusion induces irreversible oxidative stress damage and cardiomyocyte cell death (Murphy and Steenbergen, 2008)
These results demonstrated that propofol can prevent the oxygen glucose deprivation/reoxygenation (OGD/R)-induced increase in the intracellular reactive oxygen species (ROS) level and cell apoptosis rate in H9c2 cells
We examined whether propofol could ameliorate the DNA damage induced by oxidative stress in OGD/R

Summary

Introduction

Myocardial ischemia injury followed by reperfusion induces irreversible oxidative stress damage and cardiomyocyte cell death (Murphy and Steenbergen, 2008). Propofol inhibits I/R injuries in various experimental animal and cellular models by reducing the generation of ROS, scavenging free radicals, protecting the cell membrane and mitochondrial function from lipid peroxidation, and suppressing apoptosis (Corcoran et al, 2006; Jovic et al, 2012; Li et al, 2015). Prolonged production of ROS causes irreversible damage to cell membrane, organelles, and to the nucleus. It remains unexplored whether propofol protects against DNA damage induced by ischemia/reperfusion in cardiomyocytes

Methods

Results

Conclusion