雄黄通过ROS依赖的线粒体途径诱导HL-60细胞分化

doi:10.5246/jcps.2013.02.026

雄黄通过ROS依赖的线粒体途径诱导HL-60细胞分化

袁丽佳, 王聪, 刘伟, 刘文龙, 苟宝迪*, 张天蓝*

北京大学医学部化学生物学系, 北京 100191

收稿日期:2012-11-18 修回日期:2013-01-15 出版日期:2013-03-18 发布日期:2013-03-18
通讯作者: 苟宝迪*, 张天蓝*

Realgar induces differentiation through ROS-dependent mitochondrial pathway in HL-60 cells

Lijia Yuan, Cong Wang, Wei Liu, Wenlong Liu, Baodi Gou*, Tianlan Zhang*

Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2012-11-18 Revised:2013-01-15 Online:2013-03-18 Published:2013-03-18
Contact: Baodi Gou*, Tianlan Zhang*

摘要/Abstract

摘要：

含砷药物在传统中药中用于治疗多种疾病, 其中雄黄近年来被用于治疗急性早幼粒细胞白血病, 其疗效与三氧化二砷制剂相近, 但安全性相对较高。在雄黄纳米微粒诱导的HL-60细胞 (人早幼粒白血病细胞) 分化早期, 细胞内活性氧水平降低; p38 MAPK抑制剂 (SB202190) 增强雄黄的诱导分化作用, 而线粒体膜通透性转运孔抑制剂 (环孢菌素A) 减弱雄黄的诱导分化作用。这些实验结果表明, 雄黄诱导的HL-60细胞分化与细胞内活性氧水平的降低和线粒体膜通透性转运孔的开放密切相关。该研究为探索含砷抗白血病药物的分子机制提供了新的线索。

关键词: 雄黄, 细胞分化, 活性氧物种, 线粒体膜通透性转运孔, HL-60细胞

Abstract:

Realgar (As4S4), as a mineral drug in traditional Chinese medicine, is currently used as the remedy for acute promyelocytic leukemia and has been proven to have relatively milder side effects as compared to the arsenolite (As2O3)-based drugs. We have previously demonstrated that realgar induces differentiation in HL-60 cells, and the differentiation is associated with serine/threonine protein phosphatases, MAPK signaling pathways, and mitochondrial transmembrane potential decrease. In this study, we further explore the roles of mitochondrial permeability transition pore and reactive oxygen species (ROS) in realgar-induced differentiation in HL-60 cells. The differentiation was preceded by marked changes in the cellular level of ROS, and could be enhanced by SB202190, a p38 MAPK inhibitor. In addition, the efficacy of realgar was suppressed by closing the MPTP with an inhibitor. Taken together, these findings indicate that the opening of MPTP and the alteration of ROS generation were involved in realgar-induced differentiation.

Key words: Realgar, Cell differentiation, Reactive oxygen species, Mitochondrial permeability transition pore, HL-60 cells

中图分类号:

R915

Supporting:

Foundation item: The Project of National Base for Talent Training in Basic Science (Grant No. J0830836).
^*Corresponding author. Tel.: 86-10-82801539

袁丽佳, 王聪, 刘伟, 刘文龙, 苟宝迪*, 张天蓝*. 雄黄通过ROS依赖的线粒体途径诱导HL-60细胞分化[J]. , DOI: 10.5246/jcps.2013.02.026.

Lijia Yuan, Cong Wang, Wei Liu, Wenlong Liu, Baodi Gou*, Tianlan Zhang* . Realgar induces differentiation through ROS-dependent mitochondrial pathway in HL-60 cells[J]. , DOI: 10.5246/jcps.2013.02.026.

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