In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells
In vitro effect of cyclosporin A, mitomycin C and prednisolone on cell kinetics in cultured human umbilical vein endothelial cells
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DOI：
10.1016/j.thromres.2004.09.001
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发表时间：
2005-01-01
影响因子：
7.5
通讯作者：
Aizawa, Y
中科院分区：
文献类型：
--
作者：
Seki, Y;Toba, K;Aizawa, Y
前言：血管内皮细胞损伤在微血管血栓形成中起着重要作用。材料与方法：应用体外培养的人脐静脉内皮细胞，观察环孢素A、丝裂霉素C和/或强的松龙对细胞周期的影响，以及强的松龙对内皮细胞的保护作用。结果：环孢素A和丝裂霉素C可剂量依赖性地使培养的人脐静脉内皮细胞增殖停滞于G1期，而丝裂霉素C则抑制细胞DNA合成，使细胞周期停滞，并抑制Brdurd掺入S期。强的松龙本身也使细胞周期停滞于G1期，对丝裂霉素C的损伤有保护作用。环孢素A和强的松龙对细胞周期的抑制作用是可逆的，而丝裂霉素C则不可逆。人脐静脉内皮细胞表达的高度磷酸化的视网膜母细胞瘤蛋白在丝裂霉素C作用下降低，培养上清液中的可溶性血栓调节蛋白水平在加入环孢素A后升高。结论：这些药物的作用可能导致细胞周期停滞，延长受损内皮细胞的修复时间。(C)2004爱思唯尔有限公司。保留所有权利。
Introduction: Vascular endothelial cell damage plays an important role in microvascular thrombogenesis. In vivo administration of cyclosporin A or mitomycin C sometimes results in thrombotic microangiopathy in patients.Materials and methods: The effects of cyclosporin A, mitomycin C and/or prednisolone on the cell cycle in cultured human umbilical vein endothelial cells were investigated to evaluate drug-induced endothelial cell damage and the protective effect of prednisolone on endothelial cells against the damage by cyclosporin A or mitomycin C in vitro.Results: The addition of cyclosporin A to cultures caused proliferation arrest in the G1-phase in a dose-dependent manner, while mitomycin C inhibited DNA synthesis, which resulted in cell cycle arrest and inhibition of BrdUrd incorporation in the S-phase. The administration of prednisolone also caused cell cycle arrest in the G1 by itself, and protected the cells from the damage caused by mitomycin C. The inhibitory effects of cyclosporin A and prednisolone on the cell cycle were reversible, while mitomycin C was not. The highly phosphorylated retinoblastoma protein expressed in human umbilical vein endothelial cells decreased in the presence of mitomycin C. Soluble thrombomodulin levels in the culture supernatant were elevated by the addition of cyclosporin A.Conclusion: These effects of the drugs may cause the cell cycle arrest and the prolonged repair of damaged endothelial cells in patients. (C) 2004 Elsevier Ltd. All rights reserved.