title: Mitochondrial DNA oxidative damage contributes to cardiomyocyte ischemia/reperfusion-injury in rats: cardioprotective role of lycopene.
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.
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Rongchuan
authors: R
authors: Yue
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Xuewei
authors: X
authors: Xia
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Jiahui
authors: J
authors: Jiang
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Dezhong
authors: D
authors: Yang
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Yu
authors: Y
authors: Han
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Cardiovascular Research Center & Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania.
authors: Xiongwen
authors: X
authors: Chen
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Yue
authors: Y
authors: Cai
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Liangpeng
authors: L
authors: Li
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Wei Eric
authors: WE
authors: Wang
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors: Chunyu
authors: C
authors: Zeng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002338:Carotenoids / Q000008:administration & dosage*; D004249:DNA Damage / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics; D000077276:Lycopene; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D002338:Carotenoids; D000077276:Lycopene