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运用蛋白质组学研究三氧化二砷诱导K562细胞凋亡过程中核基质蛋白的变化

Proteome analysis of nuclear matrix proteins during arsenic trioxide induced apoptosis in K562 cells
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摘要 目的:探讨三氧化二砷 (As2O3 )在体外对慢性粒细胞性白血病细胞系K562细胞核基质蛋白的影响。方法:用DNA梯度电泳观察As2O3 作用后K562细胞凋亡的情况。单向、双向电泳观察As2O3 对K562细胞核基质蛋白分布影响。结果: 2. 5μmol/LAs2O3 处理 72h后,DNA电泳已能检测到发生凋亡的K562细胞,但早在As2O3 处理 48h时, 即能观察到核基质蛋白分布的改变,此时尚不能观察到凋亡特征性的DNA片段梯形条带。双向电泳可检测出 200多个核基质蛋白点,其中约 18个点与As2O3 处理相关。结论:As2O3 对K562细胞的影响是时间和剂量依赖性的。双向电泳检测As2O3 对K562核基质蛋白分布的影响较DNA梯度电泳检测更为敏感。核基质蛋白成分可能是砷作用的靶蛋白,并且可能是药物发挥抗癌作用的关键点之一。 Objective: To investigate arsenic trioxide (As 2O 3) -target interactions at the level of nuclear matrix (NM) in chronic myelogenous leukemia cell line K562 by proteomics. Methods: DNA fragmentation analysis was used for As 2O 3 induced apoptosis of K562 cells. The nuclear matrix proteins were analyzed by high-resolution two-dimensional gel electrophoresis and computer-assisted image analysis. Results: While more than 200 protein spots were shared among the nuclear matrices, about 18 distinct spots were found characteristic of As 2O 3 treated cells. Onset of mass mange apoptosis, and the profiling of nuclear matrix proteins had been alternated and it was a more sensitive indicator than nucleosomal DNA fragmentation against As 2O 3 treatment. Conclusion: As 2O 3 induced apoptosis in K562 cells in a dose-time-dependent manner. As 2O 3 might be clinically useful in treatment of chronic myelogenous leukemia and the changes of nuclear matrix proteins in the treated cells can be used as a useful indicator for the treatment.
出处 《北京大学学报(医学版)》 CAS CSCD 北大核心 2005年第2期163-166,共4页 Journal of Peking University:Health Sciences
基金 国家自然科学基金(30271672)资助~~
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