Prosurvival roles mediated by the PERK signaling pathway effectively prevent excessive endoplasmic reticulum stress-induced skeletal muscle loss during high-stress conditions of hibernation
Prosurvival roles mediated by the PERK signaling pathway effectively prevent excessive endoplasmic reticulum stress-induced skeletal muscle loss during high-stress conditions of hibernation
复制标题
PERK信号通路介导的促生存作用可有效防止冬眠高应激条件下过度内质网应激引起的骨骼肌损失
DOI：
10.1002/jcp.28572
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发表时间：
2019
影响因子：
5.6
通讯作者：
Gao Yunfang
中科院分区：
文献类型：
--
作者：
Zhang Jie;Wei Yanhong;Qu Ting;Wang Zhe;Xu Shenhui;Peng Xin;Yan Xia;Chang Hui;Wang Huiping;Gao Yunfang
Stress conditions like hypoxia, ischemia, and ischemia/reperfusion can trigger excessive endoplasmic reticulum stress (ERS), which can lead to cell apoptosis‐induced skeletal muscle atrophy in non‐hibernators. However, although hibernators experience multiple stress conditions during hibernation, their skeletal muscles appear to be well protected. We hypothesize that hibernators effectively avoid cell apoptosis, at least partially, by controlling ERS level. Here, we focused on the potential occurrence of ERS and how hibernators cope with it during different hibernation states. Results indicated that the protein expression levels of glucose‐regulated protein 78 (GRP78), phosphorylated PKR‐like ER protein kinase, phosphorylated eukaryotic translation initiation factor 2α (p‐eIF2α), and activating transcription factor 4 were significantly increased during hibernation, but primarily recovered in posthibernation. In the torpor‐arousal cycle, the expression levels of the above indicators were lower during inter‐bout arousal (IBA) than that during late torpor (LT). However, there was no change in C/EBP homologous protein expression and no apoptosis in skeletal muscles during the different hibernation states. In conclusion, the upregulation of p‐eIF2α and GRP78 were identified as two crucial mechanisms mediated by the PERK signaling pathway to alleviate elevated ERS. The downregulation of ERS during IBA may be a unique countermeasure for hibernating squirrels to prevent excessive ERS. Thus, these special anti‐excessive ERS abilities of ground squirrels contribute to the prevention of skeletal muscle cell apoptosis during hibernation.
