Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene

J Cell Physiol. 2015 Sep;230(9):2128-41. doi: 10.1002/jcp.24941.

Abstract

Mitochondrial (mt) dysfunction and oxidative stress are involved in the pathogenesis of ischemia/reperfusion (I/R)-injury. Lycopene, a lipophilic antioxidant found mainly in tomatoes and in other vegetables and fruits, can protect mtDNA against oxidative damage. However, the role of mtDNA in myocardial I/R-injury is unclear. In the present study, we aimed to determine if and how lycopene protects cardiomyocytes from I/R-injury. In both in vitro and in vivo studies, I/R-injury increased mt 8-hydroxyguanine (8-OHdG) content, decreased mtDNA content and mtDNA transcription levels, and caused mitochondrial dysfunction in cardiomyocytes. These effects of I/R injury on cardiomycoytes were blocked by pre-treatment with lycopene. MtDNA depletion alone was sufficient to induce cardiomyocyte death. I/R-injury decreased the protein level of a key activator of mt transcription, mitochondrial transcription factor A (Tfam), which was blocked by lycopene. The protective effect of lycopene on mtDNA was associated with a reduction in mitochondrial ROS production and stabilization of Tfam. In conclusion, lycopene protects cardiomyocytes from the oxidative damage of mtDNA induced by I/R-injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Carotenoids / administration & dosage*
  • DNA Damage / drug effects
  • DNA, Mitochondrial / drug effects
  • DNA, Mitochondrial / genetics
  • Lycopene
  • Myocardial Reperfusion Injury / drug therapy*
  • Myocardial Reperfusion Injury / pathology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology*
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Rats

Substances

  • Antioxidants
  • DNA, Mitochondrial
  • Carotenoids
  • Lycopene