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首页> 外文期刊>Cell biology international. >Nuclear extrusion precedes discharge of genomic DNA fibers during tunicamycin-induced neutrophil extracellular trap-osis (NETosis)-like cell death in cultured human leukemia cells
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Nuclear extrusion precedes discharge of genomic DNA fibers during tunicamycin-induced neutrophil extracellular trap-osis (NETosis)-like cell death in cultured human leukemia cells

机译：在培养的白血病细胞中衣霉素诱导的中性粒细胞胞外诱捕（NETosis）样细胞死亡期间，核挤压先于基因组DNA纤维释放。

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摘要

We previously reported that the nucleoside antibiotic tunicamycin (TN), a protein glycosylation inhibitor triggering unfolded protein response (UPR), induced neutrophil extracellular trap-osis (NETosis)-like cellular suicide and, thus, discharged genomic DNA fibers to extracellular spaces in a range of human myeloid cell lines under serum-free conditions. In this study, we further evaluated the effect of TN on human promyelocytic leukemia HL-60 cells using time-lapse microscopy. Our assay revealed a previously unappreciated early event induced by TN-exposure, in which, at 30-60min after TN addition, the cells extruded their nuclei into the extracellular space, followed by discharge of DNA fibers to form NET-like structures. Intriguingly, neither nuclear extrusion nor DNA discharge was observed when cells were exposed to inducers of UPR, such as brefeldin A, thapsigargin, or dithiothreitol. Our findings revealed novel nuclear dynamics during TN-induced NETosis-like cellular suicide in HL-60 cells and suggested that the toxicological effect of TN on nuclear extrusion and DNA discharge was not a simple UPR.
机译：我们先前曾报道过核苷抗生素衣霉素（TN）是一种蛋白质糖基化抑制剂，可触发未折叠的蛋白质反应（UPR），诱导中性粒细胞胞外诱集（NETosis）样细胞自杀，因此将基因组DNA纤维释放到了细胞外空间中。无血清条件下人类骨髓细胞系的范围。在这项研究中，我们使用延时显微镜进一步评估了TN对人早幼粒细胞白血病HL-60细胞的作用。我们的测定揭示了由TN暴露诱导的先前未曾意识到的早期事件，其中在添加TN后30-60分钟，细胞将其细胞核挤出到细胞外空间，然后排出DNA纤维以形成NET样结构。有趣的是，当细胞暴露于UPR诱导剂（如布雷菲德菌素A，毒胡萝卜素或二硫苏糖醇）时，既未观察到核挤压也未观察到DNA释放。我们的发现揭示了TN诱导HL-60细胞发生NETosis样细胞自杀期间的新型核动力学，并暗示TN对核挤压和DNA释放的毒理作用不是简单的UPR。

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