氨肽酶抑制剂Bestatin通过激活半胱天冬酶3诱导HL-60细胞凋亡  

Aminopeptidase inhibitor Bestatin induces HL-60 cell apoptosis through activating caspase 3

作　　者：林茂芳[1] 何静松[1] 蔡真[1] 钱文斌[1] 

机构地区：[1]浙江大学医学院附属第一医院血液病研究所,杭州310006

出　　处：《中华血液学杂志》2001年第7期348-350,共3页Chinese Journal of Hematology

摘　　要：目的　研究半胱天冬酶 3在国产氨肽酶N抑制剂Bestatin(商品名百士欣 ,BS)诱导人白血病细胞凋亡过程中的变化及其意义。方法　用光学显微镜观察细胞形态结构的改变 ,通过DNA片段原位末端标记法及流式细胞术 (FCM)检测细胞凋亡。用发色底物法检测细胞半胱天冬酶 3活性。Rhodamin(Rh) 12 3染色后 ,采用FCM检测细胞线粒体跨膜电位。结果　典型的细胞形态改变、DNA片段化、DNA末端原位标记及FCM结果 ,均证实BS能诱导HL 6 0细胞凋亡。凋亡率与药物剂量和作用时间呈依赖关系。BS诱导细胞凋亡过程中 ,半胱天冬酶 3活性明显升高 ,而AC DEVD CHO能抑制BS诱导的细胞凋亡。经BS处理的HL 6 0细胞出现线粒体跨膜电位 (ΔΨm)下降。结论　BS通过激活半胱天冬酶 3而诱导白血病细胞凋亡。Objective To study the variation and significance of caspase 3 activity in the process of amino peptidase inhibitor——bestatin(BS) inducing human leukemic cell apoptosis. Methods Cell apoptosis was evaluated by light microscopy, TUNEL labeling and flow cytometry(FCM). Caspase 3 activity was detected by colorimetry. The mitochondrial transmembrane potentials (ΔΨm) were detected by Rhodamine123 staining. Results The apoptotic morphology, apoptotic peak on FCM and positive Annexin V FITC on cell membrane showed that BS could induce HL 60 cell apoptosis in a dose and time dependent manner. Caspase 3 activity was significantly higher in the apoptotic cells than in control cells. The apoptosis induced by BS was inhibited by AC DEVD CHO. The ΔΨm of cells treated with BS declined. Conclusion BS induces apoptosis of human acute leukemic cells through activation of caspase 3.

关 键 词：细胞系 HL-60 氨肽酶类 细胞凋亡 半胱天冬酶 

分 类 号：R965[医药卫生—药理学]