Citrinin induces apoptosis in HL-60 cells via activation of the mitochondrial pathway
Citrinin induces apoptosis in HL-60 cells via activation of the mitochondrial pathway
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DOI：
10.1016/j.toxlet.2005.08.009
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发表时间：
2006-02-20
影响因子：
3.5
通讯作者：
Liu, BH
中科院分区：
文献类型：
--
作者：
Yu, FY;Liao, YC;Liu, BH
霉菌毒素柑橘素 (CTN) 是某些食品和饲料中常见的天然污染物，已知对多种哺乳动物细胞具有细胞毒性和基因毒性。为了研究暴露于CTN的细胞的死亡模式，选择人早幼粒细胞白血病(HL-60)细胞来鉴定CTN诱导的细胞凋亡过程。暴露于 CTN 24 小时后，可以清楚地观察到细胞凋亡的形态学证据，包括细胞核碎片和 DNA 阶梯形成。流式细胞术分析显示，在浓度高于50μM的CTN处理的培养物中，亚二倍体区域的凋亡细胞显着增加。Western印迹结果表明，CTN诱导加工的caspase-3、-6、-7的形成。 -9，但不是 caspase-8，呈剂量依赖性； CTN 还诱导 caspase-3 催化活性随时间增加。 HL-60中CTN引发的细胞凋亡伴随着细胞色素c从线粒体释放到细胞质。培养物中抗氧化剂的存在并不能有效抑制 CTN 诱导的细胞毒性和 caspase-3 活性。这些发现表明，CTN 通过刺激细胞色素 c 释放，随后激活多种半胱天冬酶来诱导 HL-60 细胞凋亡，但氧化应激可能在凋亡过程中不起作用。 (c) 2005 Elsevier Ireland Ltd. 保留所有权利。
The mycotoxin citrinin (CTN), a frequent natural contaminants of certain food and feeds, is known to be cytotoxic and genotoxic to various mammalian cells. To investigate the death mode of cells exposed to CTN, human promyelocytic leukemia (HL-60) cells were chosen to identify the apoptotic process induced by CTN. Morphological evidence of apoptosis, including nuclei fragmentation and DNA laddering formation, was clearly observed 24 h after exposure to CTN. Flow cytometry analysis revealed that apoptotic cells in the hypodiploid region dramatically increased in cultures treated with CTN at concentrations above 50 mu M. Results of Western blotting showed that CTN induced the formation of processed caspase-3, -6, -7. -9, but not caspase-8, in a dose-dependent manner; CTN also induced a time-dependent increase in caspase-3 catalytic activity. The apoptosis triggered by CTN in HL-60 was accompanied by the cytochrome c release from mitochondria to cytoplasm. The presence of antioxidants in cultures did not effectively suppress CTN-induced cytotoxicity and caspase-3 activity. These findings suggest that CTN induces apoptosis in HL-60 cells by stimulating cytochrome c release followed by activation of multiple caspases, but oxidative stress may not play a role in the apoptotic process. (c) 2005 Elsevier Ireland Ltd. All rights reserved.