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Uranium induces apoptosis in lung epithelial cells

机译:铀诱导肺上皮细胞凋亡

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Uranium is a naturally occurring radioactive material present everywhere in the environment. It is toxic because of its chemical or radioactive properties. Uranium enters environment mainly from mines and industry and cause threat to human health by accumulating in lungs as a result of inhalation. In our previous study, we have shown the effectiveness of antioxidant system response to the oxidative stress induced by uranyl acetate (UA) in rat lung epithelial (LE) cells. As part of our continuing studies; here, we investigated the mechanism underlying when LE cells are exposed to different concentration of UA. Oxidative stress may lead to apoptotic signaling pathways. LE cells treated with 0.25, 0.5 and 1 mM of UA results in dose and time-dependent increase in activity of both caspases-3 and -8. Increase in the concentration of cytochrome-c oxidase in cytosol was seen in LE cells treated with 1 mM UA as a result of mitochondria membrane permeability. The cytochrome-c leakage may trigger the apoptotic pathway. TUNEL assay performed in LE cells treated with 1 mM of UA showed significant incorporation of dNTPs in the nucleus after 24 h. In the presence of the caspase inhibitors, we observed the significant decrease in the activity of caspases-8 and -3 in 0.5 and 1 mM UA-treated LE cells.
机译:铀是自然存在的放射性物质,存在于环境中的各处。由于其化学或放射性性质,它是有毒的。铀主要通过矿山和工业进入环境,并由于吸入而在肺中积累,从而对人体健康造成威胁。在我们之前的研究中,我们显示了抗氧化剂系统对大鼠肺上皮(LE)细胞中由乙酸铀酰(UA)诱导的氧化应激反应的有效性。作为我们继续学习的一部分;在这里,我们研究了LE细胞暴露于不同浓度的UA时的潜在机制。氧化应激可能导致凋亡信号通路。用0.25、0.5和1 mM UA处理的LE细胞导致caspases-3和-8活性的剂量和时间依赖性增加。由于线粒体膜通透性,在用1 mM UA处理的LE细胞中,发现细胞溶质中细胞色素c氧化酶的浓度增加。细胞色素c泄漏可能触发凋亡途径。在用1 mM UA处理的LE细胞中进行的TUNEL分析显示,在24小时后,dNTPs在细胞核中显着掺入。在存在胱天蛋白酶抑制剂的情况下,我们观察到0.5和1 mM UA处理的LE细胞中caspases-8和-3的活性显着降低。

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