Lycopene Protects against Hypoxia/Reoxygenation Injury by Alleviating ER Stress Induced Apoptosis in Neonatal Mouse Cardiomyocytes

• Published in: PloS one 2015-08, Vol.10 (8), p.e0136443-e0136443
• Main Authors: Xu, Jiqian, Hu, Houxiang, Chen, Bin, Yue, Rongchuan, Zhou, Zhou, Liu, Yin, Zhang, Shuang, Xu, Lei, Wang, Huan, Yu, Zhengping
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - drug effects; AMP-Activated Protein Kinases - metabolism; Analysis; Anesthesiology; Animals; Animals, Newborn; Anoxia; Antioxidants - therapeutic use; Apoptosis; Apoptosis - drug effects; Attenuation; BAX protein; Bcl-2 protein; Blotting, Western; Cardiology; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Care and treatment; Carotenoids - therapeutic use; Caspase; Caspase-12; Caspase-3; Cell cycle; Cells, Cultured; CHOP protein; Endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; Enzyme Activation - drug effects; Free radicals; Gene expression; Health aspects; Heart attacks; Heart diseases; Hospitals; Hypoxia; Hypoxia - drug therapy; Influence; Injury prevention; Ischemia; Kinases; Laboratory animals; Lycopene; Mice; Mice, Inbred C57BL; mRNA; Myocardial ischemia; Myocardium; Myocytes, Cardiac - chemistry; Myocytes, Cardiac - drug effects; Neonates; Newborn babies; Newborn infants; Oxidative stress; Oxygen; Pharmacology; Phosphorylation; Polyclonal antibodies; Protein synthesis; Proteins; Reactive oxygen species; Reactive Oxygen Species - analysis; Real-Time Polymerase Chain Reaction; Reperfusion; Reperfusion Injury - prevention & control; Stress; Stresses; Thapsigargin; Therapeutic applications
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0136443

Endoplasmic reticulum (ER) stress induced apoptosis plays a pivotal role in myocardial ischemia/reperfusion (I/R)-injury. Inhibiting ER stress is a major therapeutic target/strategy in treating cardiovascular diseases. Our previous studies revealed that lycopene exhibits great pharmacological potential in protecting against the I/R-injury in vitro and vivo, but whether attenuation of ER stress (and) or ER stress-induced apoptosis contributes to the effects remains unclear. In the present study, using neonatal mouse cardiomyocytes to establish an in vitro model of hypoxia/reoxygenation (H/R) to mimic myocardium I/R in vivo, we aimed to explore the hypothesis that lycopene could alleviate the ER stress and ER stress-induced apoptosis in H/R-injury. We observed that lycopene alleviated the H/R injury as revealed by improving cell viability and reducing apoptosis, suppressed reactive oxygen species (ROS) generation and improved the phosphorylated AMPK expression, attenuated ER stress as evidenced by decreasing the expression of GRP78, ATF6 mRNA, sXbp-1 mRNA, eIF2α mRNA and eIF2α phosphorylation, alleviated ER stress-induced apoptosis as manifested by reducing CHOP/GADD153 expression, the ratio of Bax/Bcl-2, caspase-12 and caspase-3 activity in H/R-treated cardiomyocytes. Thapsigargin (TG) is a potent ER stress inducer and used to elicit ER stress of cardiomyocytes. Our results showed that lycopene was able to prevent TG-induced ER stress as reflected by attenuating the protein expression of GRP78 and CHOP/GADD153 compared to TG group, significantly improve TG-caused a loss of cell viability and decrease apoptosis in TG-treated cardiomyocytes. These results suggest that the protective effects of lycopene on H/R-injury are, at least in part, through alleviating ER stress and ER stress-induced apoptosis in neonatal mouse cardiomyocytes.