DJ-1 plays an obligatory role in the cardioprotection of delayed hypoxic preconditioning against hypoxia/reoxygenation-induced oxidative stress through maintaining mitochondrial complex I activity

Cell Biochem Funct. 2018 Apr;36(3):147-154. doi: 10.1002/cbf.3326. Epub 2018 Feb 12.

Abstract

DJ-1 was recently reported to mediate the cardioprotection of delayed hypoxic preconditioning (DHP) by suppressing hypoxia/reoxygenation (H/R)-induced oxidative stress, but its mechanism against H/R-induced oxidative stress during DHP is not fully elucidated. Here, using the well-established cellular model of DHP, we again found that DHP significantly improved cell viability and reduced lactate dehydrogenase release with concurrently up-regulated DJ-1 protein expression in H9c2 cells subjected to H/R. Importantly, DHP efficiently improved mitochondrial complex I activity following H/R and attenuated H/R-induced mitochondrial reactive oxygen species (ROS) generation and subsequent oxidative stress, as demonstrated by a much smaller decrease in reduced glutathione/oxidized glutathione ratio and a much smaller increase in intracellular ROS and malondialdehyde contents than that observed for the H/R group. However, the aforementioned effects of DHP were antagonized by DJ-1 knockdown with short hairpin RNA but mimicked by DJ-1 overexpression. Intriguingly, pharmacological inhibition of mitochondria complex I with Rotenone attenuated all the protective effects caused by DHP and DJ-1 overexpression, including maintenance of mitochondria complex I and suppression of mitochondrial ROS generation and subsequent oxidative stress. Taken together, this work revealed that preserving mitochondrial complex I activity and subsequently inhibiting mitochondrial ROS generation could be a novel mechanism by which DJ-1 mediates the cardioprotection of DHP against H/R-induced oxidative stress damage.

Keywords: DJ-1; delayed hypoxic preconditioning; hypoxia/reoxygenation; mitochondrial complex I; oxidative stress.

MeSH terms

  • Animals
  • Cells, Cultured
  • Electron Transport Complex I / metabolism*
  • Hypoxia / metabolism*
  • Ischemic Preconditioning*
  • Mitochondria / metabolism*
  • Oxidative Stress*
  • Oxygen / metabolism*
  • Protective Agents / metabolism*
  • Protein Deglycase DJ-1 / metabolism*
  • Rats
  • Reactive Oxygen Species / metabolism

Substances

  • Protective Agents
  • Reactive Oxygen Species
  • PARK7 protein, rat
  • Protein Deglycase DJ-1
  • Electron Transport Complex I
  • Oxygen