Resveratrol attenuates myocardial hypoxia/reoxygenation-induced cell apoptosis through DJ-1-mediated SIRT1-p53 pathway

Biochem Biophys Res Commun. 2019 Jun 25;514(2):401-406. doi: 10.1016/j.bbrc.2019.04.165. Epub 2019 Apr 30.

Abstract

Resveratrol, a multi-functional phytoalexin, has been well indicated to exert cardioprotective effects by weakening ischemia/reperfusion (I/R) injury, and cell apoptosis is a vital way in I/R injury. SIRT1-p53 pathway has strong significance in regulating cell apoptosis. DJ-1 can directly bind to SIRT1 and stimulate the activity of SIRT1-p53. Therefore, the current study was determined whether Resveratrol attenuates hypoxia/reoxygenation (H/R)-induced cell apoptosis, and whether DJ-1-mediated SIRT1 activation involves in the cardioprotective effects of Resveratrol. The results showed that remarkable decrease in the number of apoptotic cells along with reduction of lactate dehydrogenase release and restoration of cell viability emerged when Resveratrol was applied in the H9c2 cells exposed to H/R. Moreover, Resveratrol increased DJ-1 expression and promoted the interaction of DJ-1 with SIRT1, which further contributed to subsequent restoration of SIRT1 activity and decrease of acetylation level of p53. However, above cardioprotective effects of Resveratrol were abrogated by DJ-1 siRNA and SIRT1 specific inhibitor Sirtinol. In conclusion, the current study demonstrated that Resveratrol suppressed H/R-induced cell apoptosis, which may be conducted by up-regulating DJ-1, and later activating SIRT1 activity and subsequently inhibiting p53 acetylation level in the H9c2 cells.

Keywords: Apoptosis; Cardioprotection; DJ-1; Hypoxia/reoxygenation injury; Resveratrol; SIRT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Apoptosis / drug effects*
  • Cardiotonic Agents / pharmacology*
  • Cell Hypoxia*
  • Cell Line
  • Cell Survival
  • Enzyme Activation
  • L-Lactate Dehydrogenase / metabolism
  • Myocardial Ischemia / pathology*
  • Myocardial Reperfusion Injury / prevention & control*
  • Protein Binding
  • Protein Deglycase DJ-1 / biosynthesis
  • Protein Deglycase DJ-1 / metabolism*
  • Rats
  • Resveratrol / pharmacology*
  • Sirtuin 1 / metabolism*
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Cardiotonic Agents
  • Tp53 protein, rat
  • Tumor Suppressor Protein p53
  • L-Lactate Dehydrogenase
  • PARK7 protein, rat
  • Protein Deglycase DJ-1
  • Sirtuin 1
  • Resveratrol