The steroid hormone 20-hydroxyecdysone promotes switching from autophagy to apoptosis by increasing intracellular calcium levels
The steroid hormone 20-hydroxyecdysone promotes switching from autophagy to apoptosis by increasing intracellular calcium levels
复制标题
类固醇激素 20-羟基蜕皮激素通过增加细胞内钙水平促进自噬向细胞凋亡的转变
DOI：
10.1016/j.ibmb.2016.10.004
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发表时间：
2016-12-01
影响因子：
3.8
通讯作者：
Zhao, Xiao-Fan
中科院分区：
文献类型：
--
作者：
Li, Yong-Bo;Li, Xiang-Ru;Zhao, Xiao-Fan
自噬调节细胞存活(或在某些情况下调节细胞死亡)，而细胞凋亡调节细胞死亡。然而，自噬与细胞凋亡之间的关系及其调控机制尚不清楚。我们报道了类固醇激素20-羟基蜕皮酮(20E)通过增加鳞翅目昆虫棉铃虫中肠细胞内钙水平来促进从自噬向凋亡的转换。在20E调控下的中肠程序性细胞死亡过程中依次发生自噬和凋亡，其中低浓度的20E诱导微管相关蛋白1轻链3磷脂酰乙醇胺(LC3-II，又称自噬相关基因8，ATG8)的表达和自噬。高浓度的20E诱导ATG5裂解为NtATG5，原caspase-3裂解为活性caspase-3，导致自噬向细胞凋亡的转变。通过敲除ATG5、ATG7或ATG12或用自噬抑制剂3-甲基腺嘌呤阻断自噬，可抑制20E诱导的自噬和细胞凋亡。用凋亡抑制剂Ac-DEVD-CHO阻断细胞凋亡并不能阻止20E诱导的自噬，提示细胞凋亡依赖于自噬。ATG5基因敲除可导致化蛹异常和化蛹时间延迟。高浓度的20E可诱导细胞内高水平的钙离子、NtATG5和活化的caspase-3，从而介导细胞自噬向细胞凋亡的转变。阻断20E介导的细胞内钙离子升高导致NtATG5和活化的caspase-3减少，抑制自噬向凋亡的转化，从而促进细胞存活。20E诱导细胞内钙离子浓度升高，从而将自噬细胞的存活转换为凋亡性细胞死亡。(C)2016爱思唯尔有限公司。保留所有权利。
Autophagy regulates cell survival (or cell death in several cases), whereas apoptosis regulates cell death. However, the relationship between autophagy and apoptosis and the regulative mechanism is unclear. We report that steroid hormone 20-hydroxyecdysone (20E) promotes switching from autophagy to apoptosis by increasing intracellular calcium levels in the midgut of the lepidopteran insect Helicoverpa armigera. Autophagy and apoptosis sequentially occurred during midgut programmed cell death under 20E regulation, in which lower concentrations of 20E induced microtubule-associated protein 1 light chain 3 phosphatidylethanolamine (LC3-II, also known as autophagy-related gene 8, ATG8) expression and autophagy. High concentrations of 20E induced cleavage of ATG5 to NtATG5 and pro-caspase-3 to active caspase-3, which led to a switch from autophagy to apoptosis. Blocking autophagy by knockdown of ATG5, ATG7, or ATG12, or with the autophagy inhibitor 3-methyladenine, inhibited 20E-induced autophagy and apoptosis. Blocking apoptosis by using the apoptosis inhibitor Ac-DEVD-CHO did not prevent 20E-induced autophagy, suggesting that apoptosis relies on autophagy. ATG5 knockdown resulted in abnormal pupation and delayed pupation time. High concentrations of 20E induced high levels of intracellular Ca2+, NtATG5, and active caspase-3, which mediated the switch from autophagy to apoptosis. Blocking 20E-mediated increase of cellular Ca2+ caused a decrease of NtATG5 and active caspase-3 and repressed the transformation from autophagy to apoptosis, thereby promoting cell survival. 20E induces an increase in the concentration of intracellular Ca2+, thereby switching autophagic cell survival to apoptotic cell death. (C) 2016 Elsevier Ltd. All rights reserved.