BSO对内皮细胞氧化还原状态的影响

Effects of buthionine sulfoxine on the redox state of human umbilical vein endothelial cells cultured with K562 cells conditioned media

目的 探讨人脐静脉血管内皮细胞(humanumbilicalveinendothelialcells, HUVEC)在慢性髓性白血病细胞株K562细胞条件培养基作用下氧化还原状态的变化与其增殖活性间的关系,观察谷胱甘肽合成抑制剂丁胱亚磺酰亚胺(buthioninesulfoxine, BSO)在上述条件下对HUVECs的作用,为探索相应的抗肿瘤血管生成治疗策略提供新思路。方法 用K562细胞条件培养基、谷胱甘肽合成抑制剂共同或单独处理HUVEC,检测HUVEC细胞内氧化还原状态以及细胞活力的改变。结果 K562细胞条件培养基明显促进内皮细胞的增殖,并促进内皮细胞氧化型与还原型谷胱甘肽(GSSG与GSH)、辅酶Ⅱ(NADP+与NADPH)两对氧化和还原性物质同时增高,但GSSG/GSH、NADP+ /NADPH比值未变。BSO显示出对HUVEC生长的明显抑制,引起HUVEC中GSH、NADPH含量明显降低、GSSG/GSH、NADP+ /NADPH比值升高;在K562细胞条件培养基的同时作用下,BSO对HUVEC的生长抑制作用增强, 使细胞内GSSG/GSH、NADP+ /NADPH比值进一步提高。结论 慢性髓性白血病细胞条件培养基使得血管内皮细胞对BSO的生长抑制作用更加敏感,其机制与内皮细胞氧化还原状态的改变密切相关。

Aim To investigate the role of K562 cells conditioned media on redox state of human umbilical vein endothelial cells (HUVECs) and the role of buthionine sulfoxine(BSO), a selective inhibitor of γ-glutamylcysteine synthetase, on HUVECs cultured with K562 cells conditioned media. Methods Glutathione(GSH)、oxidized glutathione (GSSG)、NADP^+、NADPH concentration and the viability of HUVECs under various conditions were determinated. Results GSSG、GSH、NADP^+、NADPH concentration of HUVECs increased when HUVECs were cultured with K562 cells conditioned media. The inhibition of HUVECs growth by Bso enhanced when K562 cells conditioned media were used at the same time. Conclusion Under the effection of chronic myelogenous leukemia cells conditioned media, endothelial cells may be more sensitive to BSO.