Journal article
The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study
Biochemical and biophysical research communications, Vol.478(1), pp.87-92
09/09/2016
DOI: 10.1016/j.bbrc.2016.07.088
PMID: 27453341
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.
•Nrf2/Ucp2 deficiency leads to alteration of glutathione homeostasis.•Nrf2 regulates expression of genes in glutathione generation and utilization.•Ucp2 affects glutathione metabolism by regulating hepatic efflux of glutathione.•Nrf2 deficiency may not aggravate oxidative stress in Ucp2-deficient mice.
Details
- Title: Subtitle
- The role of nuclear factor E2-Related factor 2 and uncoupling protein 2 in glutathione metabolism: Evidence from an in vivo gene knockout study
- Creators
- Yanyan Chen - The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China; The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA.Yuanyuan Xu - China Medical UniversityHongzhi Zheng - The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, PR China; The Hamner Institutes for Health Sciences, Research Triangle Park, NC, USA.Jingqi Fu - China Medical UniversityYongyong Hou - China Medical UniversityHuihui Wang - China Medical UniversityQiang Zhang - Emory UniversityMasayuki Yamamoto - Tohoku UniversityJingbo Pi - China Medical University
- Resource Type
- Journal article
- Publication Details
- Biochemical and biophysical research communications, Vol.478(1), pp.87-92
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.bbrc.2016.07.088
- PMID
- 27453341
- ISSN
- 0006-291X
- eISSN
- 1090-2104
- Grant note
- name: Chinese Nature Science Foundation, award: 81573106, 81573187; name: Liaoning Pandeng Scholar Program; name: Startup Funding of China Medical University; DOI: 10.13039/100000002, name: National Institutes of Health Grant, award: ES016005; name: Program for Liaoning Innovative Research Team in University, award: LT2015028
- Language
- English
- Date published
- 09/09/2016
- Academic Unit
- Neurology
- Record Identifier
- 9984303011402771
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