Temporal coordination of the transcription factor response to H<sub>2</sub>O<sub>2</sub> stress.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38653977.
- Also identified by DOI 10.1038/s41467-024-47837-w and PMC identifier 11039679.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Oxidative stress from excess H<sub>2</sub>O<sub>2</sub> activates transcription factors that restore redox balance and repair oxidative damage. Although many transcription factors are activated by H<sub>2</sub>O<sub>2</sub>, it is unclear whether they are activated at the same H<sub>2</sub>O<sub>2</sub> concentration, or time. Dose-dependent activation is likely as oxidative stress is not a singular state and exhibits dose-dependent outcomes including cell-cycle arrest and cell death. Here, we show that transcription factor activation is both dose-dependent and coordinated over time. Low levels of H<sub>2</sub>O<sub>2</sub> activate p53, NRF2 and JUN. Yet under high H<sub>2</sub>O<sub>2</sub>, these transcription factors are repressed, and FOXO1, NF-κB, and NFAT1 are activated. Time-lapse imaging revealed that the order in which these two groups of transcription factors are activated depends on whether H<sub>2</sub>O<sub>2</sub> is administered acutely by bolus addition, or continuously through the glucose oxidase enzyme. Finally, we provide evidence that 2-Cys peroxiredoxins control which group of transcription factors are activated.
Medical subject headings
- Hydrogen Peroxide
- Oxidative Stress
- Transcription Factors