Dying cells protect survivors from radiation-induced cell death in Drosophila.
Dying cells protect survivors from radiation-induced cell death in Drosophila.
复制标题
DOI：
10.1371/journal.pgen.1004220
复制
发表时间：
2014-03
期刊：
影响因子：
4.5
通讯作者：
Su TT
中科院分区：
文献类型：
--
作者：
Bilak A;Uyetake L;Su TT
我们报告了一种现象，其中诱导细胞死亡的各种手段在翅成虫盘的果蝇幼虫导致激活的抗凋亡的microRNA，矮脚鸡。垂死细胞附近的细胞也变得更难被电离辐射（IR）诱导的凋亡杀死。这两个禁令激活和增加保护IR需要受体酪氨酸激酶Tie，这是我们在一个基因筛选的禁令修改器。Tie突变体对辐射高度敏感，增加Ban基因剂量可挽救Tie突变体的辐射敏感性。我们提出，垂死的细胞通过Tie激活存活细胞中的禁令，使后者更难杀死，从而保护组织并确保生物体存活。我们报告的保护作用不同于经典的辐射旁观者效应，在辐射的细胞的邻居变得更容易死亡。这种保护作用也不同于先前描述的导致果蝇幼虫盘中附近细胞增殖的垂死细胞的作用。如果在哺乳动物中保守，死亡细胞使其余细胞更难被IR杀死的现象可能对涉及顺序使用细胞毒性剂和放射治疗的治疗产生影响。在多细胞生物中，细胞存在于其他细胞的环境中，一个细胞的行为会影响其他细胞。这种相互作用的结果不仅包括细胞命运的选择，还包括生与死的决定。在果蝇幼虫的翅原基中，垂死的细胞释放促有丝分裂信号，刺激邻近的细胞增殖。这种效应被认为是为了补偿细胞损失并帮助组织再生。我们在这里报告说，在相同的实验系统中，垂死的细胞激活了存活细胞中的促生存microRNA，bantam。这导致对电离辐射（IR）杀伤作用的保护增加。Ban的激活需要Tie，Tie编码受体酪氨酸激酶。tie和ban突变体幼虫对红外线的杀伤非常敏感，这表明这里描述的反应对辐射暴露后生物体的生存很重要。
We report a phenomenon wherein induction of cell death by a variety of means in wing imaginal discs of Drosophila larvae resulted in the activation of an anti-apoptotic microRNA, bantam. Cells in the vicinity of dying cells also become harder to kill by ionizing radiation (IR)-induced apoptosis. Both ban activation and increased protection from IR required receptor tyrosine kinase Tie, which we identified in a genetic screen for modifiers of ban. tie mutants were hypersensitive to radiation, and radiation sensitivity of tie mutants was rescued by increased ban gene dosage. We propose that dying cells activate ban in surviving cells through Tie to make the latter cells harder to kill, thereby preserving tissues and ensuring organism survival. The protective effect we report differs from classical radiation bystander effect in which neighbors of irradiated cells become more prone to death. The protective effect also differs from the previously described effect of dying cells that results in proliferation of nearby cells in Drosophila larval discs. If conserved in mammals, a phenomenon in which dying cells make the rest harder to kill by IR could have implications for treatments that involve the sequential use of cytotoxic agents and radiation therapy. In multicellular organisms where cells exist in the context of other cells, the behavior of one affects the others. The consequences of such interactions include not just cell fate choices but also life and death decisions. In the wing primordia of Drosophila melanogaster larvae, dying cells release mitogenic signals that stimulate the neighbors to proliferate. Such an effect is proposed to compensate for cell loss and help regenerate the tissue. We report here that, in the same experimental system, dying cells activate a pro-survival microRNA, bantam, in surviving cells. This results in increased protection from the killing effect of ionizing radiation (IR). Activation of ban requires tie, which encodes a receptor tyrosine kinase. tie and ban mutant larvae are hypersensitive to killing by IR, suggesting that the responses described here are important for organismal survival following radiation exposure.
登录
查看更多内容
影响因子：
10.5
作者：
Kadener, Sebastian;Menet, Jerome S.;Rosbash, Michael
通讯作者：
Rosbash, Michael
影响因子：
9.2
作者：
Boulan, Laura;Martin, David;Milan, Marco
通讯作者：
Milan, Marco
影响因子：
11.8
作者：
Fan, Yun;Bergmann, Andreas
通讯作者：
Bergmann, Andreas
Caspase 3 介导的癌症放射治疗过程中肿瘤细胞增殖的刺激。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hay, BA;Wassarman, DA;Rubin, GM
通讯作者：
Rubin, GM