High-resolution kinetics and modeling of hydrogen peroxide degradation in live cells

Ali Altintas, Kristian Davidsen, Christian Garde, Uffe Hasbro Mortensen, Jens Christian Brasen, Thomas Sams, Christopher Workman

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Although the role of oxidative stress factors and their regulation is well studied, the temporal dynamics of stress recovery is still poorly understood. In particular, measuring the kinetics of stress recovery in the first minutes after acute exposure provides a powerful technique for assessing the role of regulatory proteins or enzymes through the use of mutant backgrounds. This project endeavors to screen the temporal dynamics of intracellular oxidant levels in live cells as a function of gene deletion in the budding yeast, Saccharomyces cerevisiae. Using the detailed time dynamics of extra- and intra-cellular peroxide we have developed a mathematical model that describes two distinct kinetic processes, an initial rapid degradation in the first 10–20 min followed by a slower process. Using this model, a qualitative comparison allowed us to assign the dependence of temporal events to genetic factors. Surprisingly, we found that the deletion of transcription factors Yap1p or Skn7p was sufficient to disrupt the establishment of the second degradation phase but not the initial phase. A better fundamental
understanding of the role protective factors play in the recovery from oxidative stress may lead to strategies for protecting or sensitizing cell to this stress.
Original languageEnglish
JournalFree Radical Biology & Medicine
Volume101
Pages (from-to)143–153
ISSN0891-5849
DOIs
Publication statusPublished - 2016

Keywords

  • Yeast
  • Oxidative stress response
  • Kinetic modeling

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