Microcystin-LR causes the collapse of actin filaments in primary human hepatocytes

Microcystin-LR causes the collapse of actin filaments in primary human hepatocytes
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DOI:
10.1016/s0166-445x(03)00108-5
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发表时间:
2003-10-08
期刊:
影响因子:
4.5
通讯作者:
Suput, DA
Suput, DA
中科院分区:
环境科学与生态学2区
文献类型:
--
作者:
Batista, T;de Sousa, G;Suput, DA

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微囊藻毒素(microcytin - lr, MCLR)是蛋白磷酸酶1和2A的有效抑制剂,可引起大鼠肝细胞凋亡的细胞骨架细丝和形态学改变。也有报告说,它造成了若干人死亡和生病的病例。由于目前尚未对微囊藻毒素油对人肝细胞的影响进行研究,因此本研究的目的是评估MCLR对人原代肝细胞的毒性。肝细胞在12.5-50 nM的MCLR中孵育3、6和9 h,用荧光探针固定并染色肌动蛋白丝和核。光谱激光扫描共聚焦显微镜显示,在mclr处理的原代人肝细胞中,肌动蛋白网塌陷到细胞中心,类似于对大鼠肝细胞的描述。细胞在冒泡,分裂,彼此分离。受累细胞的细胞核凝聚。综上所述,本研究证实了MCLR对人原代肝细胞具有毒性,可能是急性蓝藻中毒后观察到的肝衰竭病例的原因。(C) 2003 Elsevier B.V.版权所有
Microcystin-LR (MCLR) is a potent inhibitor of protein phosphatases 1 and 2A and causes alterations in cytoskeletal filaments and morphological changes that underlie apoptosis in rat hepatocytes. It has also been reported that it caused several cases of human deaths and illness. As no study on the effect of microcystins Oil human hepatocytes was done, yet, the aim of the study is to evaluate the toxicity of MCLR on primary human hepatocytes. The hepatocytes were incubated in 12.5-50 nM MCLR for 3, 6 and 9 h, fixed and stained with fluorescent probes for actin filaments and nuclei. Spectral laser-scanning confocal microscopy revealed that in the MCLR-treated primary human hepatocytes the actin mesh collapsed into the center of the cell, similarly as it has been described for rat hepatocytes. Cells were blebbing, fragmenting, and separated from each other. The nuclei in the affected cells condensed. In conclusion, this Study confirms that MCLR is toxic to primary human hepatocytes, and it may be responsible for the liver failure cases observed after acute cyanobacterial poisoning. (C) 2003 Elsevier B.V. All rights reserved.