Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Proteomics Research Center, National Yang-Ming University, Taipei, 11221, Taiwan.
Commun Biol. 2020 Nov 11;3(1):658. doi: 10.1038/s42003-020-01378-2.
Bats hibernate to survive stressful conditions. Examination of whole cell and mitochondrial proteomes of the liver of Myotis ricketti revealed that torpid bats had endoplasmic reticulum unfolded protein response (UPR), global reduction in glycolysis, enhancement of lipolysis, and selective amino acid metabolism. Compared to active bats, torpid bats had higher amounts of phosphorylated serine/threonine kinase (p-Akt) and UPR markers such as PKR-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4). Torpid bats also had lower amounts of the complex of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65)/I-κBα. Cellular redistribution of 78 kDa glucose-regulated protein (GRP78) and reduced binding between PERK and GRP78 were also seen in torpid bats. Evidence of such was not observed in fasted, cold-treated, or normal mice. These data indicated that bats activate Akt, Nrf2, and NF-κB via the PERK-ATF4 regulatory axis against endoplasmic reticulum stresses during hibernation.
蝙蝠通过冬眠来应对压力环境。对蹄蝠肝脏的全细胞和线粒体蛋白质组进行检测，结果表明，冬眠蝙蝠存在内质网未折叠蛋白反应（UPR）、糖酵解整体减少、脂解增强和选择性氨基酸代谢。与活跃的蝙蝠相比，冬眠蝙蝠中磷酸化丝氨酸/苏氨酸激酶（p-Akt）和 UPR 标志物如蛋白激酶 R 样内质网激酶（PERK）和激活转录因子 4（ATF4）的含量更高。冬眠蝙蝠中 Kelch 样 ECH 相关蛋白 1（Keap1）、红细胞生成素相关因子 2（Nrf2）和核因子 kappa-轻链增强子的活性 B 细胞（NF-κB）（p65）/I-κBα复合物的含量也较低。在冬眠蝙蝠中还观察到 78 kDa 葡萄糖调节蛋白（GRP78）的细胞重新分布以及 PERK 和 GRP78 之间的结合减少。在禁食、冷处理或正常小鼠中未观察到这种情况。这些数据表明，蝙蝠通过 PERK-ATF4 调节轴激活 Akt、Nrf2 和 NF-κB，以应对冬眠期间的内质网应激。
