首页> 外文期刊>American Journal of Physiology >Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages.
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Reactive oxygen species and caspase activation mediate silica-induced apoptosis in alveolar macrophages.

机译:活性氧和胱天蛋白酶激活介导二氧化硅诱导的肺泡巨噬细胞凋亡。

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摘要

Alveolar macrophages (AMs) are the principal target cells of silica and occupy a key position in the pathogenesis of silica-related diseases. Silica has been found to induce apoptosis in AMs, whereas its underlying mechanisms involving the initiation and execution of apoptosis are largely unknown. The main objective of the present study was to examine the form of cell death caused by silica and the mechanisms involved. Silica-induced apoptosis in AMs was evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling assay and cell cycle/DNA content analysis. The elevated level of reactive oxygen species (ROS), caspase-9 and caspase-3 activation, and poly(ADP-ribose) polymerase (PARP) cleavage in silica-treated AMs were also determined. The results showed that there was a temporal pattern of apoptotic events in silica-treated AMs, starting with ROS formation and followed by caspase-9 and caspase-3 activation, PARP cleavage, and DNA fragmentation. Silica-induced apoptosis was significantly attenuated by a caspase-3 inhibitor, N-acetyl-Asp-Glu-Val-Asp aldehyde, and ebselen, a potent antioxidant. These findings suggest that apoptosis is an important form of cell death caused by silica exposure in which the elevated ROS level that results from silica exposure may act as an initiator, leading to caspase activation and PARP cleavage to execute the apoptotic process.
机译:肺泡巨噬细胞(AMs)是二氧化硅的主要靶细胞,在二氧化硅相关疾病的发病机理中占有重要地位。已经发现二氧化硅诱导AM中的细胞凋亡,但是其涉及细胞凋亡的起始和执行的基本机制尚不清楚。本研究的主要目的是研究由二氧化硅引起的细胞死亡形式及其机制。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定和细胞周期/ DNA含量分析评估了二氧化硅诱导的AMs凋亡。还确定了二氧化硅处理的AM中高水平的活性氧(ROS),caspase-9和caspase-3活化以及聚(ADP-核糖)聚合酶(PARP)裂解。结果表明,二氧化硅处理的AM中存在凋亡事件的时间模式,从ROS形成开始,然后是caspase-9和caspase-3激活,PARP裂解和DNA片段化。 caspase-3抑制剂,N-乙酰基-Asp-Glu-Val-Asp醛和强效抗氧化剂ebselen大大减轻了二氧化硅诱导的凋亡。这些发现表明凋亡是由二氧化硅暴露引起的细胞死亡的重要形式,其中二氧化硅暴露引起的升高的ROS水平可以充当引发剂,导致胱天蛋白酶激活和PARP裂解以执行凋亡过程。

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