Lycopene protects against hypoxia/reoxygenation-induced apoptosis by preventing mitochondrial dysfunction in primary neonatal mouse cardiomyocytes.

Rongchuan Yue,Zhou Zhou,Ke Li,Shuang Zhang,Lei Xu,Kai Hang Yiu,Tao Luo,Houxiang Hu,Zhengping Yu,Ferenc Gallyas

doi:10.1371/journal.pone.0050778

Abstract

BackgroundHypoxia/reoxygenation(H/R)-induced apoptosis of cardiomyocytes plays an important role in myocardial injury. Lycopene is a potent antioxidant carotenoid that has been shown to have protective properties on cardiovascular system. The aim of the present study is to investigate the potential for lycopene to protect the cardiomyocytes exposed to H/R. Moreover, the effect on mitochondrial function upon lycopene exposure was assessed.Methods and FindingsPrimary cardiomyocytes were isolated from neonatal mouse and established an in vitro model of H/R which resembles ischemia/reperfusion in vivo. The pretreatment of cardiomyocytes with 5 µM lycopene significantly reduced the extent of apoptosis detected by TUNEL assays. To further study the mechanism underlying the benefits of lycopene, interactions between lycopene and the process of mitochondria-mediated apoptosis were examined. Lycopene pretreatment of cardiomyocytes suppressed the activation of the mitochondrial permeability transition pore (mPTP) by reducing the intracellular reactive oxygen species (ROS) levels and inhibiting the increase of malondialdehyde (MDA) levels caused by H/R. Moreover, the loss of mitochondrial membrane potential, a decline in cellular ATP levels, a reduction in the amount of cytochrome c translocated to the cytoplasm and caspase-3 activation were observed in lycopene-treated cultures.ConclusionThe present results suggested that lycopene possesses great pharmacological potential in protecting against H/R-induced apoptosis. Importantly, the protective effects of lycopene may be attributed to its roles in improving mitochondrial function in H/R-treated cardiomyocytes.

Highlights

Myocardial infarction is the leading cause of premature death in the United States and many developed countries [1,2]
The present results suggested that lycopene possesses great pharmacological potential in protecting against H/R-induced apoptosis
The protective effects of lycopene may be attributed to its roles in improving mitochondrial function in H/R-treated cardiomyocytes

Summary

Introduction

Myocardial infarction is the leading cause of premature death in the United States and many developed countries [1,2]. Reperfusion after myocardial infarction is essential for reestablishing the blood flow in order to prevent the myocardium from further damage. The exact mechanism is uncertain, several hypotheses have been proposed to describe the pathogenesis of myocardial I/R-injury: including oxygen radical hypothesis, calcium overload hypothesis and inflammatory hypothesis [3]. The exploration for a new intrinsic or exogenous method and potential therapeutic agents that aims at reducing the I/R-injury has become an area of intensive research. Lycopene has the strongest ability to scavenge free radicals; being 10-fold, 47-fold and 100-fold more effective at quenching singlet oxygen than a-tocopherol, bcarotene and vitamin E respectively [5,6]. The aim of the present study is to investigate the potential for lycopene to protect the cardiomyocytes exposed to H/R. The effect on mitochondrial function upon lycopene exposure was assessed

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Results

Conclusion