BmATG5 and BmATG6 mediate apoptosis following autophagy induced by 20-hydroxyecdysone or starvation
BmATG5 and BmATG6 mediate apoptosis following autophagy induced by 20-hydroxyecdysone or starvation
复制标题
BmATG5 和 BmATG6 在 20-羟基蜕皮激素或饥饿诱导的自噬后介导细胞凋亡
DOI：
10.1080/15548627.2015.1134079
复制
发表时间：
2016-01-01
期刊：
影响因子：
13.3
通讯作者：
Cao, Yang
中科院分区：
文献类型：
--
作者：
Xie, Kun;Tian, Ling;Cao, Yang
摘要自噬和细胞凋亡在机体的发育和疾病中起着重要作用。由于自噬的双重作用，自噬和凋亡之间的功能关系是复杂的。20-羟基蜕皮激素（20 E）处理或饥饿诱导的Bm-12细胞中，自噬先于细胞凋亡。响应于20 E或饥饿，BmATG 8被快速切割并与PE缀合以形成BmATG 8-PE;随后，BmATG 5和BmATG 6分别被切割成BmATG 5-tN和BmATG 6-C。通过RNAi减少BmAtg 5或BmAtg 6的表达降低了20 E处理或饥饿后经历自噬和凋亡的细胞比例。BmAtg 5或BmAtg 6的过表达诱导自噬，但不凋亡的情况下的刺激，但促进自噬和凋亡诱导的20 E或饥饿。值得注意的是，切割位点缺失的BmAtg 5或BmAtg 6的过表达增加了自噬，但不增加由20 E或饥饿诱导的凋亡，而BmAtg 5-tN和BmAtg 6-C的过表达能够直接触发凋亡或促进诱导的凋亡。总之，被切割成BmATG 5-tN和BmATG 6-C，BmATG 5和BmATG 6介导在20 E或饥饿诱导的自噬后的细胞凋亡，这反映了自噬先于细胞凋亡在中肠中的对虾变态。
ABSTRACT Autophagy and apoptosis, which could be induced by common stimuli, play crucial roles in development and disease. The functional relationship between autophagy and apoptosis is complex, due to the dual effects of autophagy. In the Bombyx Bm-12 cells, 20-hydroxyecdysone (20E) treatment or starvation-induced cell death, with autophagy preceding apoptosis. In response to 20E or starvation, BmATG8 was rapidly cleaved and conjugated with PE to form BmATG8–PE; subsequently, BmATG5 and BmATG6 were cleaved into BmATG5-tN and BmATG6-C, respectively. Reduction of expression of BmAtg5 or BmAtg6 by RNAi decreased the proportion of cells undergoing both autophagy and apoptosis after 20E treatment or starvation. Overexpression of BmAtg5 or BmAtg6 induced autophagy but not apoptosis in the absence of the stimuli, but promoted both autophagy and apoptosis induced by 20E or starvation. Notably, overexpression of cleavage site-deleted BmAtg5 or BmAtg6 increased autophagy but not apoptosis induced by 20E or starvation, whereas overexpression of BmAtg5-tN and BmAtg6-C was able to directly trigger apoptosis or promote the induced apoptosis. In conclusion, being cleaved into BmATG5-tN and BmATG6-C, BmATG5 and BmATG6 mediate apoptosis following autophagy induced by 20E or starvation in Bombyx Bm-12 cells, reflecting that autophagy precedes apoptosis in the midgut during Bombyx metamorphosis.