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Effects of JUN and NFE2L2 knockdown on oxidative status and NFE2L2/AP-1 targets expression in HeLa cells in basal conditions and upon sub-lethal hydrogen peroxide treatment

  • Anna A. Belanova
  • Victor K. Chmykhalo
  • Maxim S. Makarenko
  • Olga V. Lyangasova
  • Maria M. Belousova
  • Anzhela A. Aleksandrova
  • Peter V. Zolotukhin
Original Article
  • 17 Downloads

Abstract

Although NFE2L2 transcription factor is considered to make the most significant contribution to the NFE2L2/AP-1-pathway-dependent antioxidants regulation in the human cell, AP-1 has the potential to provide significant backup and even play an equal role in the cell. Considering this, the present study is focused on revealing how JUN, an AP-1 component, and NFE2L2 contribute to regulation of four target genes containing AREs with embedded TREs-SQSTM1, FTH1, HMOX1 and CBR3 and to cellular oxidative status in general in basal conditions and under pro-oxidative influence. NFE2L2 and JUN were down-regulated in HeLa cells using siRNA-mediated knockdown approach. These cells were subsequently exposed to 400 µM hydrogen peroxide in the medium or equal volume of sterile water. They revealed some evidence of both backup functioning and competing between the two factors. Importantly, JUN demonstrated a high level of participation (inc. as a negative regulator) in functioning of the classic NFE2L2 targets and in cellular oxidative status establishment in general. One of the key findings was a dramatic increase in JUN expression following NFE2L2 knockdown in basal conditions. The both AP-1 and NFE2L2 sub-pathways equally determine the outcome of the NFE2L2/AP-1 pathway activation induced by various stimuli, and the outcome is stimulus type- and stimulus-intensity-specific and results from either of the two eventually dominating sub-pathways.

Keywords

NFE2L2 NRF2 AP-1 Oxidative status Antioxidant signaling 

Notes

Acknowledgements

This project was funded by the Russian Ministry for Science and Education, Project #6.6762.2017. The funding source had no influence on study design, collection, analysis and interpretation of the data, writing and submission of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors claim no conflicts of interests regarding the present paper exist.

Supplementary material

11033_2018_4412_MOESM1_ESM.xls (52 kb)
Supplementary material 1 (XLS 51 KB)

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Biomedical Innovations LLCRostov-on-DonRussia
  2. 2.Academy of Biology and BiotechnologySouthern Federal UniversityRostov-on-DonRussia
  3. 3.Department of English Language for Natural Sciences FacultiesSouthern Federal UniversityRostov-on-DonRussia

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