Prosurvival roles mediated by the PERK signaling pathway effectively prevent excessive endoplasmic reticulum stress‐induced skeletal muscle loss during high‐stress conditions of hibernation
| Autor: | Yanhong Wei, Xia Yan, Ting Qu, Zhe Wang, Huiping Wang, Jie Zhang, Xin Peng, Shenhui Xu, Hui Chang, Yunfang Gao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Physiology Eukaryotic Initiation Factor-2 Clinical Biochemistry Apoptosis Biology eIF-2 Kinase 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Hibernation medicine Animals Humans Initiation factor Muscle Skeletal Protein kinase A Endoplasmic Reticulum Chaperone BiP Heat-Shock Proteins Endoplasmic reticulum Sciuridae Skeletal muscle Cell Biology Torpor Endoplasmic Reticulum Stress Cell biology Muscular Atrophy 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis Phosphorylation Signal transduction Transcription Factor CHOP Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 234:19728-19739 |
| ISSN: | 1097-4652 0021-9541 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text