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Quantifying redox transcription factor dynamics as a tool to investigate redox signalling

Lookup NU author(s): Lewis Tomalin, Dr Elizabeth Veal

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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


Abstract

© 2024 The Authors. A critical feature of the cellular antioxidant response is the induction of gene expression by redox-sensitive transcription factors. In many cells, activating these transcription factors is a dynamic process involving multiple redox steps, but it is unclear how these dynamics should be measured. Here, we show how the dynamic profile of the Schizosaccharomyces pombe Pap1 transcription factor is quantifiable by three parameters: signal amplitude, signal time and signal duration. In response to increasing hydrogen peroxide concentrations, the Pap1 amplitude decreased while the signal time and duration showed saturable increases. In co-response plots, these parameters showed a complex, non-linear relationship to the mRNA levels of four Pap1-regulated genes. We also demonstrate that hydrogen peroxide and tert-butyl hydroperoxide trigger quantifiably distinct Pap1 activation profiles and transcriptional responses. Based on these findings, we propose that different oxidants and oxidant concentrations modulate the Pap1 dynamic profile, leading to specific transcriptional responses. We further show how the effect of combination and pre-exposure stresses on Pap1 activation dynamics can be quantified using this approach. This method is therefore a valuable addition to the redox signalling toolbox that may illuminate the role of dynamics in determining appropriate responses to oxidative stress.


Publication metadata

Author(s): Lind DJ, Naidoo KC, Tomalin LE, Rohwer JM, Veal EA, Pillay CS

Publication type: Article

Publication status: Published

Journal: Free Radical Biology and Medicine

Year: 2024

Volume: 218

Pages: 16-25

Print publication date: 01/06/2024

Online publication date: 02/04/2024

Acceptance date: 01/04/2024

Date deposited: 17/04/2024

ISSN (print): 0891-5849

ISSN (electronic): 1873-4596

Publisher: Elsevier Inc.

URL: https://doi.org/10.1016/j.freeradbiomed.2024.04.004

DOI: 10.1016/j.freeradbiomed.2024.04.004


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Funding

Funder referenceFunder name
117864
138096
BB/F015895/1
BB/T002484/1
BBSRC
National Research Foundation (NRF) of South Africa
Newcastle University Global Challenges Academy

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