The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study

Yanyan Chen, Yuanyuan Xu, Hongzhi Zheng, Jingqi Fu, Yongyong Hou, Huihui Wang, Qiang Zhang, Masayuki Yamamoto, Jingbo Pi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)87-92
Number of pages6
JournalBiochemical and biophysical research communications
Volume478
Issue number1
DOIs
Publication statusPublished - 2016 Sep 9

Keywords

  • Glutathione
  • Nuclear factor-erythroid 2-related factor 2
  • Oxidative stress
  • Uncoupling protein 2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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