Chen Yanyan, Xu Yuanyuan, Zheng Hongzhi, Fu Jingqi, Hou Yongyong, Wang Huihui, Zhang Qiang, Yamamoto Masayuki, Pi Jingbo
The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China; The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA.
School of Public Health, China Medical University, Shenyang, Liaoning, PR China.
Biochem Biophys Res Commun. 2016 Sep 9;478(1):87-92. doi: 10.1016/j.bbrc.2016.07.088. Epub 2016 Jul 21.
Nuclear factor E2-related factor 2 (NRF2) and uncoupling protein 2 (UCP2) are indicated to protect from oxidative stress. They also play roles in the homeostasis of glutathione. However, the detailed mechanisms are not well understood. In the present study, we found Nrf2-knockout (Nrf2-KO) mice exhibited altered glutathione homeostasis and reduced expression of various genes involved in GSH biosynthesis, regeneration, utilization and transport in the liver. Ucp2-knockout (Ucp2-KO) mice exhibited altered glutathione homeostasis in the liver, spleen and blood, as well as increased transcript of cystic fibrosis transmembrane conductance regulator in the liver, a protein capable of mediating glutathione efflux. Nrf2-Ucp2-double knockout (DKO) mice showed characteristics of both Nrf2-KO and Ucp2-KO mice. But no significant difference was observed in DKO mice when compared with Nrf2-KO or Ucp2-KO mice, except in blood glutathione levels. These data suggest that ablation of Nrf2 and Ucp2 leads to disrupted GSH balance, which could result from altered expression of genes involved in GSH metabolism. DKO may not evoke more severe oxidative stress than the single gene knockout.
核因子E2相关因子2（NRF2）和解偶联蛋白2（UCP2）被认为具有抵御氧化应激的作用。它们在谷胱甘肽的稳态中也发挥作用。然而，具体机制尚不清楚。在本研究中，我们发现Nrf2基因敲除（Nrf2-KO）小鼠的谷胱甘肽稳态发生改变，肝脏中参与谷胱甘肽生物合成、再生、利用和转运的各种基因的表达降低。Ucp2基因敲除（Ucp2-KO）小鼠的肝脏、脾脏和血液中的谷胱甘肽稳态发生改变，肝脏中囊性纤维化跨膜传导调节因子的转录增加，该蛋白能够介导谷胱甘肽外流。Nrf2-Ucp2双基因敲除（DKO）小鼠表现出Nrf2-KO和Ucp2-KO小鼠的特征。但与Nrf2-KO或Ucp2-KO小鼠相比，DKO小鼠除了血液谷胱甘肽水平外没有观察到显著差异。这些数据表明，Nrf2和Ucp2的缺失导致谷胱甘肽平衡被破坏，这可能是由于参与谷胱甘肽代谢的基因表达改变所致。与单基因敲除相比，DKO可能不会引发更严重的氧化应激。
