Wang Jianfeng, Zhang Li, Zhang Ying, Luo Meiling, Wu Qiong, Yu Lijun, Chu Haiying
Department of Neurology, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
Central Laboratory, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
Toxicol In Vitro. 2015 Mar;29(2):380-8. doi: 10.1016/j.tiv.2014.10.015. Epub 2014 Nov 15.
Long-term abuse of alcohol results in chronic alcoholic myopathy which is associated with increased oxidative stress. Ginkgo biloba extract (EGB) is widely used as a therapeutic agent to treat certain cardiovascular and neurological disorders. Although EGB is known to possess antioxidant functions and potent cytoprotective effects, its protective mechanism on alcohol-induced oxidative damage in C2C12 myoblasts remains unclear. In this study, we investigated the cytoprotective mechanisms of EGB against alcohol-derived oxidative stress in mouse C2C12 myoblasts. Challenge with alcohol (100mM) caused an increase in intracellular reactive oxygen species in mouse C2C12 myoblasts, which was not alleviated by treatment with EGB. These results indicate that EGB does not seem to act as an ROS scavenger in this experimental model. Additionally, EGB produced activation of ERK and JNK [two major mitogen-activated protein kinases (MAPKs)], an increase in the nuclear level of nuclear factor erythroid-2-related factor 2 (Nrf2) and upregulation of heme oxygenase-1 (HO-1, a stress-responsive protein with antioxidant function). Pretreatment with inhibitors of MAPKs PD98059 (a specific inhibitor of ERK), SP600125 (a specific inhibitor of JNK) abolished both EGB-induced Nrf2 nuclear translocation and HO-1 up-regulation. We conclude that EGB confers cytoprotective effects from oxidative stress induced by alcohol in mouse C2C12 myoblasts depend on transcriptional upregulation of HO-1 by EGB via the MAPKs/Nrf2 pathway.
长期酗酒会导致慢性酒精性肌病，这与氧化应激增加有关。银杏叶提取物（EGB）被广泛用作治疗某些心血管和神经系统疾病的治疗剂。尽管已知EGB具有抗氧化功能和强大的细胞保护作用，但其对酒精诱导的C2C12成肌细胞氧化损伤的保护机制仍不清楚。在本研究中，我们研究了EGB对小鼠C2C12成肌细胞酒精源性氧化应激的细胞保护机制。用酒精（100mM）刺激导致小鼠C2C12成肌细胞内活性氧增加，而EGB处理并不能缓解这种情况。这些结果表明，在该实验模型中，EGB似乎不充当ROS清除剂。此外，EGB可激活ERK和JNK[两种主要的丝裂原活化蛋白激酶（MAPK）]，增加核因子红细胞2相关因子2（Nrf2）的核水平，并上调血红素加氧酶-1（HO-1，一种具有抗氧化功能的应激反应蛋白）。用MAPK抑制剂PD98059（ERK的特异性抑制剂）、SP600125（JNK的特异性抑制剂）预处理可消除EGB诱导的Nrf2核转位和HO-1上调。我们得出结论，EGB对小鼠C2C12成肌细胞酒精诱导的氧化应激具有细胞保护作用，这取决于EGB通过MAPKs/Nrf2途径对HO-1的转录上调。
