Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Distinct roles of Nrf1 and Nrf2 in monitoring the reductive stress response to dithiothreitol (DTT)

Reziyamu Wufur, Zhuo Fan, Jianxin Yuan, Ze Zheng, Shaofan Hu, Guiyin Sun, View ORCID ProfileYiguo Zhang
doi: https://doi.org/10.1101/2022.06.24.497421
Reziyamu Wufur
1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China
2Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhuo Fan
1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianxin Yuan
1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ze Zheng
1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shaofan Hu
1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China
2Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guiyin Sun
2Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: yiguozhang@cqu.edu.cn sunriseok@126.com
Yiguo Zhang
1The Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering and Faculty of Medical Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China
2Chongqing University Jiangjin Hospital, School of Medicine, Chongqing University, No. 725 Jiangzhou Avenue, Dingshan Street, Jiangjin District, Chongqing 402260, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yiguo Zhang
  • For correspondence: yiguozhang@cqu.edu.cn sunriseok@126.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Transcription factor Nrf2 (nuclear factor, erythroid 2-like 2, encoded by Nfe2l2) has been accepted as a key player in redox regulatory responses to oxidative or reductive stresses. However, it is less or not known about the potential role for Nrf1 (nuclear factor, erythroid 2-like 1, encoded by Nfe2l1) in the redox responses, particularly to reductive stress, albeit this ‘fossil-like’ factor is indispensable for cell homeostasis and organ integrity during life process. Here, we examine distinct roles of Nrf1 and Nrf2 in monitoring the defense response to 1,4–dithiothreitol (DTT, serving as a reductive stressor), concomitantly with unfolded protein response being induced by this chemical (also as an endoplasmic reticulum stressor). The results revealed that intracellular reactive oxygen species (ROS) were modestly increased in DTT-treated wild-type (WT) and Nrf1α–/– cell lines, but almost unaltered in Nrf2–/–ΔTA or caNrf2ΔN cell lines (with a genetic loss of its transactivation or N-terminal Keap1-binding domains, respectively). This chemical treatment also enabled the rate of oxidized to reduced glutathione (i.e., GSSG to GSH) to be amplified in WT and Nrf2–/–ΔTA cells, but diminished in Nrf1α–/– cells, along with no changes in caNrf2ΔN cells. Consequently, Nrf1α–/–, but not Nrf2–/–ΔTA or caNrf2ΔN, cell viability was reinforced by DTT against its cytotoxicity, as accompanied by decreased apoptosis. Further experiments unraveled that Nrf1 and Nrf2 differentially, and also synergistically, regulated DTT-inducible expression of critical genes for defending redox stress and endoplasmic reticulum stress. In addition, we have also identified that Cys342 and Cys640 of Nrf1 (as redox-sensing sites within its N-glycodomain and DNA-binding domain, respectively) are required for its protein stability and transcription activity.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 26, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Distinct roles of Nrf1 and Nrf2 in monitoring the reductive stress response to dithiothreitol (DTT)
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Distinct roles of Nrf1 and Nrf2 in monitoring the reductive stress response to dithiothreitol (DTT)
Reziyamu Wufur, Zhuo Fan, Jianxin Yuan, Ze Zheng, Shaofan Hu, Guiyin Sun, Yiguo Zhang
bioRxiv 2022.06.24.497421; doi: https://doi.org/10.1101/2022.06.24.497421
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Distinct roles of Nrf1 and Nrf2 in monitoring the reductive stress response to dithiothreitol (DTT)
Reziyamu Wufur, Zhuo Fan, Jianxin Yuan, Ze Zheng, Shaofan Hu, Guiyin Sun, Yiguo Zhang
bioRxiv 2022.06.24.497421; doi: https://doi.org/10.1101/2022.06.24.497421

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3698)
  • Biochemistry (7809)
  • Bioengineering (5689)
  • Bioinformatics (21330)
  • Biophysics (10595)
  • Cancer Biology (8199)
  • Cell Biology (11961)
  • Clinical Trials (138)
  • Developmental Biology (6777)
  • Ecology (10419)
  • Epidemiology (2065)
  • Evolutionary Biology (13900)
  • Genetics (9726)
  • Genomics (13094)
  • Immunology (8164)
  • Microbiology (20058)
  • Molecular Biology (7871)
  • Neuroscience (43147)
  • Paleontology (321)
  • Pathology (1280)
  • Pharmacology and Toxicology (2264)
  • Physiology (3362)
  • Plant Biology (7246)
  • Scientific Communication and Education (1315)
  • Synthetic Biology (2010)
  • Systems Biology (5547)
  • Zoology (1132)