ROS Regulate Caspase-Dependent Cell Delamination without Apoptosis in the Drosophila Pupal Notum
ROS Regulate Caspase-Dependent Cell Delamination without Apoptosis in the Drosophila Pupal Notum
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DOI：
10.1016/j.isci.2020.101413
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发表时间：
2020-08-21
期刊：
影响因子：
5.8
通讯作者：
Miura, Masayuki
中科院分区：
文献类型：
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作者：
Fujisawa, Yuya;Shinoda, Natsuki;Miura, Masayuki
胸融合发生在果蝇蛹背的中线，涉及上皮细胞脱层，需要凋亡信号。通过基因筛选，我们发现与超氧阴离子（O-2（中心点-））相关的NADPH氧化酶（Nox和Duox）负责caspase-3的激活和分层。我们观察到Nox在经历脱层的细胞中上调，并且脱层依赖于半胱天冬酶激活。然而，细胞形态学和碘化丙啶掺入的几乎完全缺乏表明很少有膜破坏，并表示凋亡调节。这些结果表明，大多数脱层细胞经历半胱天冬酶活化，但这种活化不足以进行凋亡。我们发现，过氧化氢酶的表达，编码过氧化氢清除剂在胞质溶胶中，增加分层和诱导凋亡的caspase-3激活的细胞核碎片。这些发现表明，O-2（中心点-）和细胞内H2 O2脱层的作用不同之前和之后的caspase-3激活，这涉及活细胞脱层。
Thorax fusion occurs in the midline of the Drosophila pupal notum and involves epithelial cell delamination requiring apoptotic signaling. By genetic screening, we found that NADPH oxidases (Nox and Duox) associated with superoxide anion (O-2(center dot-)) are responsible for caspase-3 activation and delamination. We observed that Nox is upregulated in cells that undergo delamination and that delamination depends on caspase activation. However, the cell morphology and the almost complete lack of propidium iodide incorporation suggested little membrane disruption and signified apoptotic modulation. These results demonstrate that most delaminating cells undergo caspase activation, but this activation is not sufficient for apoptosis. We showed that the expression of Catalase, encoding an H2O2 scavenger in the cytosol, increases delamination and induces apoptotic nuclear fragmentation in caspase-3-activated cells. These findings suggest that the roles of O-2(center dot-) and intracellular H2O2 for delamination differs before and after caspase-3 activation, which involves live cell delamination.