A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C-elegans
A common set of engulfment genes mediates removal of both apoptotic and necrotic cell corpses in C-elegans
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DOI：
10.1038/35046585
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发表时间：
2000-12-01
影响因子：
21.3
通讯作者：
Driscoll, M
中科院分区：
文献类型：
--
作者：
Chung, SB;Gumienny, TL;Driscoll, M
与哺乳动物兴奋性毒性细胞死亡类似，秀丽隐杆线虫中的坏死样细胞死亡（NCD）可以由过度活跃的离子通道引发。在这里，我们研究了由有毒 MEG-4 通道引起的坏死样神经元死亡中执行和调节程序性细胞死亡 (PCD) 的基因的要求。任何已知阻断 PCD 的线虫突变都不会改变坏死发生的动力学或产生的坏死尸体的总数，这提供了遗传证据，表明 NCD 和细胞凋亡的激活机制是不同的。相比之下，所有以前报道的吞噬清除凋亡尸体所需的 ced 基因，以及我们已经鉴定的新吞噬基因 ced-12，都是有效消除由不同的坏死诱导刺激产生的尸体所必需的。我们的结果表明，无论细胞死亡模式如何，一组共同的基因都可以消除细胞尸体，并首次鉴定出有序去除坏死细胞所需的秀丽隐杆线虫基因。由于吞噬机制似乎从线虫到人类都是保守的，我们的研究结果表明，高等生物中受损的坏死细胞也可能在裂解前通过受控的尸体清除过程被消除，这一假设具有重要的治疗意义。
Similar to mammalian excitotoxic cell death, necrotic-like cell death (NCD) in Caenorhabditis elegans can be initiated by hyperactive ion channels. Here we investigate the requirements for genes that execute and regulate programmed cell death (PCD) in necrotic-like neuronal death caused by a toxic MEG-4 channel. Neither the kinetics of necrosis onset nor the total number of necrotic corpses generated is altered by any C. elegans mutation known to block PCD, which provides genetic evidence that, the activating mechanisms for NCD and apoptotic cell death are distinct. In contrast, all previously reported ced genes required for phagocytotic removal of apoptotic corpses, as well as ced-12, a new engulfment gene we have identified, are required for efficient elimination of corpses generated by distinct necrosis-inducing stimuli. Our results show that a common set of genes acts to eliminate cell corpses irrespective of the mode of cell death, and provide the first identification of the C. elegans genes that are required for orderly removal of necrotic cells. As phagocytotic mechanisms seem to be conserved from nematodes to humans, our findings indicate that injured necrotic cells in higher organisms might also be eliminated before lysis through a controlled process of corpse removal, a hypothesis that has significant therapeutic implications.