Autophagic Cell Death and Apoptosis Jointly Mediate Cisatracurium Besylate-Induced Cell Injury
AbstractCisatracurium besylate is an ideal non-depolarizing muscle relaxant which is widely used in clinical application. However, some studies have suggested that cisatracurium besylate can affect cell proliferation. Moreover, its specific mechanism of action remains unclear. Here, we found that the number of GFP-LC3 (green fluoresent protein-light chain 3) positive autophagosomes and the rate of mitochondria fracture both increased significantly in drug-treated GFP-LC3 and MitoDsRed stable HeLa cells. Moreover, cisatracurium promoted the co-localization of LC3 and mitochondria and induced formation of autolysosomes. Levels of mitochondrial proteins decreased, which were reversed by the lysosome inhibitor Bafinomycin A1. Similar results with evidence of dose-dependent effects were found in both HeLa and Human Umbilical Vein Endothelial Cells (HUVECs). Cisatracurium lowered HUVEC viability to 0.16 (OD490) at 100 µM and to 0.05 (OD490) after 48 h in vitro; it increased the cell death rate to 56% at 100 µM and to 60% after 24 h in a concentration- and time-dependent manner (p < 0.01). Cell proliferation decreased significantly by four fold in Atg5 WT (wildtype) MEF (mouse embryonic fibroblast) (p < 0.01) but was unaffected in Atg5 KO (Knockout) MEF, even upon treatment with a high dose of cisatracurium. Cisatracurium induced significant increase in cell death of wild-type MEFs even in the presence of the apoptosis inhibitor zVAD. Thus, we conclude that activation of both the autophagic cell death and cell apoptosis pathways contributes to cisatracurium-mediated cell injury. View Full-Text
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Zhuang, H.; Tian, W.; Li, W.; Zhang, X.; Wang, J.; Yang, Y.; Liu, X.; Xia, Z.; Feng, D.; Zhang, L. Autophagic Cell Death and Apoptosis Jointly Mediate Cisatracurium Besylate-Induced Cell Injury. Int. J. Mol. Sci. 2016, 17, 515.
Zhuang H, Tian W, Li W, Zhang X, Wang J, Yang Y, Liu X, Xia Z, Feng D, Zhang L. Autophagic Cell Death and Apoptosis Jointly Mediate Cisatracurium Besylate-Induced Cell Injury. International Journal of Molecular Sciences. 2016; 17(4):515.Chicago/Turabian Style
Zhuang, Haixia; Tian, Weili; Li, Wen; Zhang, Xingli; Wang, Jingjing; Yang, Yue; Liu, Xin; Xia, Zhengyuan; Feng, Du; Zhang, Liangqing. 2016. "Autophagic Cell Death and Apoptosis Jointly Mediate Cisatracurium Besylate-Induced Cell Injury." Int. J. Mol. Sci. 17, no. 4: 515.
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