Abstract
Oxidative stress is a well-known biological process that occurs in all respiring cells and is involved in pathophysiological processes such as aging and apoptosis. Oxidative stress agents include peroxides such as hydrogen peroxide, cumene hydroperoxide, and linoleic acid hydroperoxide, the thiol oxidant diamide, and menadione, a generator of superoxide, amongst others. The present study analyzed the early temporal genome-wide transcriptional response of Saccharomyces cerevisiae to oxidative stress induced by the aromatic peroxide cumene hydroperoxide. The accurate dataset obtained, supported by the use of temporal controls, biological replicates and well controlled growth conditions, provided a detailed picture of the early dynamics of the process. We identified a set of genes previously not implicated in the oxidative stress response, including several transcriptional regulators showing a fast transient response, suggesting a coordinated process in the transcriptional reprogramming. We discuss the role of the glutathione, thioredoxin and reactive oxygen species-removing systems, the proteasome and the pentose phosphate pathway. A data-driven clustering of the expression patterns identified one specific cluster that mostly consisted of genes known to be regulated by the Yap1p and Skn7p transcription factors, emphasizing their mediator role in the transcriptional response to oxidants. Comparison of our results with data reported for hydrogen peroxide identified 664 genes that specifically respond to cumene hydroperoxide, suggesting distinct transcriptional responses to these two peroxides. Genes up-regulated only by cumene hydroperoxide are mainly related to the cell membrane and cell wall, and proteolysis process, while those down-regulated only by this aromatic peroxide are involved in mitochondrial function.
Highlights
Several processes expose cells to reactive oxygen species (ROS) that cause severe damage to proteins, DNA and lipids, impairing cell function
Oxidative stress is a mechanism used by immune cells to fight pathogens, a weapon that properly directed is beneficial to the host, but that can cause damage to other host cells as well
Several transcription factors have been described to be involved in this response, and perhaps the best known in yeast isYap1p, which plays a central role in the regulation of oxidative stress-responding genes in S. cerevisiae [10]
Summary
Several processes expose cells to reactive oxygen species (ROS) that cause severe damage to proteins, DNA and lipids, impairing cell function. Several transcription factors have been described to be involved in this response, and perhaps the best known in yeast isYap1p, which plays a central role in the regulation of oxidative stress-responding genes in S. cerevisiae [10]. We study the dynamics of the transcriptional response of S. cerevisiae to oxidative stress induced by CHP.
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