Li Meng, Peng Yifan, Chen Wenjun, Gao Yongjiao, Yang Maohong, Li Jingang, He Jianping
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Science, Shaanxi Normal University, Xi'an, China.
National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Science, Shaanxi Normal University, Xi'an, China.
Comp Biochem Physiol B Biochem Mol Biol. 2023 Feb-Mar;264:110811. doi: 10.1016/j.cbpb.2022.110811. Epub 2022 Nov 11.
Gansu zokor (Eospalax cansus) is a typical subterranean rodent species with resistance to ambient hypoxia. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling plays a key role in regulating redox homeostasis. However, little is known about the regulation of Nrf2 signaling in Gansu zokor. We exposed Gansu zokors and SD rats to chronic hypoxia (44 h at 10.5% O) or acute hypoxia (6 h at 6.5% O) andmeasured the activities of heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO-1)，gene expression of HO-1, NQO-1, Nrf2, Kelch-like ECH-associated protein-1 (KEAP1), and β-transducin repeat-containing protein (β-TRCP) in the brain and liver. We found that Gansu zokor increased the NQO-1 protein content and activity, HO-1 protein content in the brain, and increased HO-1 activity and mRNA level, NQO-1 activity and protein content in the liver by up regulating Nrf2 gene expression under chronic hypoxia. Although acute hypoxia enhanced the expression of Nrf2 gene, only the level of HO-1 mRNA in the liver increased. Besides, the HO-1 and NQO-1 genes in the brain, HO-1 genes and NQO-1 mRNA in the Gansu zokor liver were significantly higher than those in SD rats under normoxia. Negative regulators of Nrf2 signaling were tissue specific: KEAP1 protein decreased in the brain, and β-TRCP decreased in the liver. The Nrf2 signaling and expression of downstream antioxidant enzymes were different under different oxygen concentrations, reflecting the flexible characteristics of Gansu zokor to deal with the hypoxic environment.
甘肃鼢鼠（Eospalax cansus）是一种典型的对环境低氧具有抗性的地下啮齿动物。核因子红细胞2相关因子2（Nrf2）信号通路在调节氧化还原稳态中起关键作用。然而，关于甘肃鼢鼠中Nrf2信号通路的调控知之甚少。我们将甘肃鼢鼠和SD大鼠暴露于慢性低氧（10.5%氧气浓度下44小时）或急性低氧（6.5%氧气浓度下6小时）环境中，测量了脑和肝脏中血红素加氧酶-1（HO-1）和NAD（P）H醌氧化还原酶-1（NQO-1）的活性，以及HO-1、NQO-1、Nrf2、kelch样ECH相关蛋白-1（KEAP1）和含β-转导素重复序列蛋白（β-TRCP）的基因表达。我们发现，在慢性低氧条件下，甘肃鼢鼠通过上调Nrf2基因表达，增加了脑中NQO-1蛋白含量和活性、HO-1蛋白含量，以及肝脏中HO-1活性和mRNA水平、NQO-1活性和蛋白含量。虽然急性低氧增强了Nrf2基因的表达，但仅肝脏中HO-1 mRNA水平升高。此外，在常氧条件下，甘肃鼢鼠脑中的HO-1和NQO-1基因、肝脏中的HO-1基因和NQO-1 mRNA显著高于SD大鼠。Nrf2信号通路的负调节因子具有组织特异性：脑中KEAP1蛋白减少，肝脏中β-TRCP减少。不同氧浓度下Nrf2信号通路及下游抗氧化酶的表达不同，反映了甘肃鼢鼠应对低氧环境的灵活特性。
