谷胱甘肽合成酶抑制剂加强三氧化二砷的凋亡诱导效应

Glutathione synthesis inhibitor enhances arsenic trioxide induced apoptosis

目的 了解巯基在三氧化二砷（Ａｓ２Ｏ３） 诱导凋亡效应中的作用。方法 应用γ谷氨酰半胱氨酸合成酶抑制剂（ｂｕｔｈｉｏｎｉｎｅ ｓｕｌｆｏｘｉｍｉｎｅ，ＢＳＯ） 和Ａｓ２Ｏ３ 共同处理白血病细胞系ＮＢ４ 、ＨＬ６０、Ｕ９３７ 、ｊｕｒｋａｔ 和淋巴瘤细胞系ｎａｍａｌｗａ，通过流式细胞仪检测细胞线粒体跨膜电位（ΔΨｍ） 和凋亡细胞。结果１ ｍｍｏｌ／ＬＢＳＯ明显增加１ μｍｏｌ／ＬＡｓ２Ｏ３ 诱导的ＮＢ４ 细胞ΔΨｍ 下降和凋亡，１ μｍｏｌ／ＬＡｓ２Ｏ３ 不诱导ｎａｍａｌｗａ、ＨＬ６０、Ｕ９３７ 和ｊｕｒｋａｔ 细胞ΔΨｍ 下降和凋亡，但这些效应在Ａｓ２Ｏ３ 和ＢＳＯ同时处理后出现。结论 巯基是Ａｓ２Ｏ３

Objective To illustrate the possible role of thiols (SH groups) in arsenic trioxide (As 2O 3) induced apoptosis.Methods Leukemia (NB4, HL60, U937) and lymphoma (Jurkat and Namalwa) cell lines were treated with As 2O 3 together with buthionine sulfoximine (BSO), a selective inhibitor of γ glutamylcysteine synthetase. The mitochondrial transmembrane potentials (ΔΨm) and the percentage of cells in apoptosis were measured by means of flow cytometry.Results one mmol/L BSO significantly enhanced As 2O 3 induced ΔΨm collapse and apoptosis in NB4 cells. One μmol/L As 2O 3 did not induce the ΔΨm collapse and apoptosis in Namalwa, HL60, U937 and Jurkat cells, while these effects were induced significantly by the co treatment of 1 μmol/L As 2O 3 and 1 mmol/L BSO.Conclusion Thiols are important chemosensors of As 2O 3 induced ΔΨm collapse and apoptosis.