Cell-autonomous requirement for DNaseII in nonapoptotic cell death.
Cell-autonomous requirement for DNaseII in nonapoptotic cell death.
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DOI：
10.1038/cdd.2009.79
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发表时间：
2009-10
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
--
作者：
DNA片段化是细胞凋亡的关键组成部分，但其在非凋亡形式的细胞死亡中尚未被表征，例如坏死和自噬性细胞死亡。在哺乳动物细胞凋亡过程中，caspase激活的DNA酶（CAD）在垂死细胞中将DNA切割成核小体片段，随后DNaseII（一种酸性核酸酶）完成DNA降解，但在吞噬细胞的溶酶体内非细胞自主地起作用。在这里，我们研究的程序性细胞死亡（PCD）发生在果蝇卵巢，饥饿诱导的死亡中期卵室和发育后期的护士细胞死亡的两个例子中的DNA酶的要求。令人惊讶的是，我们发现DNaseII在发育PCD期间在保育细胞中是细胞自主需要的，这表明它在垂死细胞中起作用。死亡的护理细胞含有自噬体，表明自噬可能有助于这些形式的PCD。此外，我们提供的证据表明，在卵子发生后期发育的护士细胞PCD显示坏死的标志。这些发现表明，DNaseII可以在非凋亡性细胞死亡过程中自主降解DNA。
DNA fragmentation is a critical component of apoptosis but it has not been characterized in non-apoptotic forms of cell death, such as necrosis and autophagic cell death. In mammalian apoptosis, caspase activated DNase (CAD) cleaves DNA into nucleosomal fragments in dying cells, and subsequently DNaseII, an acid nuclease, completes the DNA degradation but acts non-cell-autonomously within lysosomes of engulfing cells. Here we examine the requirement for DNases during two examples of programmed cell death (PCD) that occur in the Drosophila melanogaster ovary, starvation-induced death of mid-stage egg chambers and developmental nurse cell death in late oogenesis. Surprisingly, we found that DNaseII was required cell-autonomously in nurse cells during developmental PCD, indicating that it acts within dying cells. Dying nurse cells contain autophagosomes, indicating that autophagy may contribute to these forms of PCD. Furthermore, we provide evidence that developmental nurse cell PCD in late oogenesis shows hallmarks of necrosis. These findings indicate that DNaseII can act cell-autonomously to degrade DNA during non-apoptotic cell death.
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