Insights into H2O2-induced signaling in Jurkat cells from analysis of gene expression.

Abstract

Hydrogen peroxide (H₂O₂) is a ubiquitous oxidant produced in a regulated manner by various enzymes in mammalian cells. H₂O₂ reversibly oxidizes thiol groups of cysteine residues to mediate intracellular signaling. While examples of H₂O_2-dependent signaling have been reported, the exact molecular mechanism(s) of signaling and the pathways affected are not well understood. Here, the transcriptomic response of Jurkat T cells to H₂O₂ was investigated to determine global effects on gene expression. With a low H₂O₂ concentration (10 µM) that did not induce an oxidative stress response or cell death, extensive changes in gene expression occurred after 4 h (6803 differentially expressed genes). Of the genes with a greater then 2-fold change in expression, 85% were upregulated suggesting that in a physiological setting H₂O₂ predominantly activates gene expression. Pathway analysis identified gene expression signatures associated with FOXO and NTRK signaling. These signatures were associated with an overlapping set of transcriptional regulators. Overall, our results provide a snapshot of gene expression changes in response to H₂O_2, which, along with further studies, will lead to new insights into the specific pathways that are activated in response to endogenous production of H₂O₂, and the molecular mechanisms of H₂O₂ signaling.