Arsenic trioxide induces the apoptosis in bone marrow mesenchymal stem cells by intracellular calcium signal and caspase-3 pathways

被引：48

作者：

Cai, Ben-Zhi ^{[1
]}

Meng, Fan-Yu ^{[1
]}

Zhu, Song-Ling ^{[1
]}

Zhao, Jing ^{[1
]}

Liu, Jia-Qi ^{[1
]}

Liu, Chan-Juan ^{[1
]}

Chen, Nan ^{[1
]}

Ye, Ming-Lei ^{[1
]}

Li, Zhong-Yu ^{[1
]}

Ai, Jing ^{[1
]}

Lu, Yan-Jie ^{[1
]}

Yang, Bao-Feng ^{[1
]}

机构：

[1] Harbin Med Coll, Dept Pharmacol, Harbin 150081, Peoples R China

来源：

TOXICOLOGY LETTERS | 2010年 / 193卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Arsenic trioxide; Apoptosis; Ca2+](i); Bone marrow mesenchymal stem cells; ACUTE PROMYELOCYTIC LEUKEMIA; MYOCARDIAL-INFARCTION; SY-5Y NEUROBLASTOMA; QT INTERVAL; APL THERAPY; GUINEA-PIG; HOMEOSTASIS; HEART; DIFFERENTIATION; TRANSPLANTATION;

D O I：

10.1016/j.toxlet.2010.01.001

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

It was previously reported that excessive arsenic trioxide would produce cardiovascular toxicity. Bone marrow mesenchymal stem cells (BMSCs) have been shown to play a supporting role in cardiovascular functions. The increasing apoptosis of BMSCs commonly would promote the development of cardiovascular diseases. Thus we hypothesize that arsenic trioxide caused apoptosis in BMSCs, which provided a better understanding of arsenic toxicity in hearts. The present study was designed to investigate the proapoptotic effects of arsenic trioxide on BMSCs and explore the mechanism underlying arsenic trioxide-induced BMSCs apoptosis. We demonstrate that arsenic trioxide significantly inhibited survival ratios of BMSCs in a concentration-dependent and time-dependent manner. The Annexin V/PI staining and terminal deoxynucleotidyl transferasemediated dUTP nick-end labelling (TUNEL) assay also showed that arsenic trioxide markedly induced the apoptosis of BMSCs. The caspase-3 activity was obviously enhanced in the presence of arsenic trioxide in a concentration-dependent manner in BMSCs. Additionally, arsenic trioxide caused the increase of intracellular free calcium ([Ca2+](i)) in rat BMSCs. BAPTA pretreatment may attenuate the apoptosis of BMSCs induced by arsenic trioxide. Taken together, arsenic trioxide could inhibit the proliferation and induce the apoptosis of BMSCs by modulating intracellular [Ca2+](i), and activating the caspase-3 activity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：173 / 178

页数：6

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