title: High-resolution kinetics and modeling of hydrogen peroxide degradation in live cells.
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 10-20min 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.
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark.
authors.forename: Ali
authors.initials: A
authors.lastname: Altıntaş
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Davidsen
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Garde
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark.
authors.forename: Uffe H
authors.initials: UH
authors.lastname: Mortensen
authors.affiliation: Biomedical Engineering, Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark.
authors.forename: J Christian
authors.initials: JC
authors.lastname: Brasen
authors.affiliation: Biomedical Engineering, Department of Electrical Engineering, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark. Electronic address: tsams@dtu.dk.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sams
authors.affiliation: Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby DK-2800, Denmark. Electronic address: cwor@dtu.dk.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Workman
mesh_terms: D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D057166:High-Throughput Screening Assays; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008658:Inactivation, Metabolic / Q000235:genetics; D007700:Kinetics; D015233:Models, Statistical; D005810:Multigene Family; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C083962:SKN7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D006861:Hydrogen Peroxide
keywords: Kinetic modeling; Oxidative stress response; Yeast