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Lookup NU author(s): Lewis Tomalin, Dr Elizabeth Veal
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 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.
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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