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ASSA14-03-14 Mitochondrial DNA damage contribute to ischemia/reperfusion-injury in rat cardiac myocytes: the protective effects of lycopene
  1. R Yue,
  2. WE Wang,
  3. X Xia,
  4. J Jiang,
  5. D Yang,
  6. Y Han,
  7. C Zeng
  1. Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, China

Abstract

Objectives Recent studies suggest that oxidative stress and mitochondrial dysfunction are involved in the pathogenesis of ischemia/reperfusion (I/R)-injury. Mitochondrial DNA (mtDNA) is highly vulnerable to oxidative stress and lycopene is found to protect mtDNA against oxidative damage. Our recent study indicates lycopene reduced I/R-injury in vitro by alleviating oxidative stress and preventing mitochondrial dysfunction. This study was aimed to determine whether mtDNA damage is involved in the I/R-injury and whether lycopene can protect cardiac myocytes from I/R-injury by inhibiting mtDNA damage.

Methods We established I/R-injury model with rat in vivo and we also established hypoxia/ reoxygenation-injury model with H9c2 cells to simulate I/R-injury in vitro. Reactive oxygen species (ROS) and mitochondrial superoxide levels were determined. Mitochondrial 8-hydroxyguanine (8-OHdG), mtDNA content and mtDNA transcript levels were detected to find out if mtDNA were damaged; The protein expression of mitochondrial transcription factor A (Tfam) in mitochondrial, a key protein for mtDNA transcription, replication and component for nucleoid organisation were also determined by western blot.

Results I/R significantly increased reactive oxygen species (ROS) production and mitochondrial superoxide levels. In addition, I/R increased mitochondrial 8-hydroxyguanine (8-OHdG) content, while reduced mtDNA content and mtDNA transcript levels. Consistent with these findings, I/R was found to decrease the protein expression of Tfam in mitochondrial. Lycopene pretreatment efficiently attenuated the oxidative damage to mtDNA induced by I/R both in vivo and in vitro.

Conclusion Our results suggest that mtDNA damage may account for I/R-injury. Lycopene has a great pharmacological potential in protecting mtDNA against the I/R-injury in the heart.

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