沈玉雷 陈国强 蔡循 贾培敏 朱新华 黄莺 陈赛娟 王振义 陈竺 200025 上海，上海第二医科大学附属瑞金医院 上海血液学研究所(沈玉雷、陈国强、蔡循、贾培敏、朱新华、陈赛娟、王振义、陈竺)；上海第二医科大学生物学教研室(黄莺) 中华肿瘤杂志 1999 0 21 4


    关键词：细胞凋亡；三氧化二砷；谷胱甘肽合成酶抑制剂；巯基 期刊 zhzlzz 0 基础研究 fur -->


    

【摘要】 目的 了解巯基在三氧化二砷(As₂ O₃ )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As₂ O₃ 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/L BSO明显增加1 μmol/L As₂ O₃ 诱导的NB4细胞ΔΨm下降和凋亡，1μmol/L As₂ O₃ 不诱导namalwa、HL60、U937和jurkat细胞ΔΨm下降和凋亡，但这些效应在As₂ O₃ 和BSO同时处理后出现。结论 巯基是As₂ O₃ 诱导细胞凋亡的重要化学感受器。

Glutathione synthesis inhibitorenhances arsenic trioxide-induced apoptosis

SHEN Yulei, CHEN Guoqiang CAI Xun, et al.Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University,Shanghai 200025

【Abstract】 Objective Toillustrate the possible role of thiols (SH-groups) in arsenic trioxide (As₂ O₃ )-inducedapoptosis.Methods Leukemia (NB4, HL60, U937) and lymphoma (Jurkat and Namalwa) cell lines were treated with As₂ O₃ together with buthioninesulfoximine (BSO), a selective inhibitor of γ-glutamylcysteine synthetase. Themitochondrial transmembrane potentials (ΔΨm) and the percentage of cells in apoptosiswere measured by means of flow cytometry.Results one mmol/L BSOsignificantly enhanced As₂ O₃ -induced ΔΨm collapse and apoptosis inNB4 cells. One μmol/L As₂ O₃ did not induce the ΔΨm collapse andapoptosis in Namalwa, HL60, U937 and Jurkat cells, while these effects were inducedsignificantly by the co-treatment of 1 μmol/L As₂ O₃ and 1 mmol/LBSO.Conclusion Thiols are important chemosensors of As₂ O₃ -inducedΔΨm collapse and apoptosis.

     ......