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. H2O2reversibly oxidises thiol groups of cysteine residues to mediate intracellular signalling. Whilst examples of H2O2dependent signalling have been reported, the exact molecular mechanism(s) of signalling and the pathways affected are not well understood. Here, the transcriptomic response of Jurkat T cells to H2O2was investigated to determine global effects on gene expression. With a low H2O2concentration (10 μM) that did not induced an oxidative stress response or cell death, extensive changes in gene expression occurred after 4 hours (6803 differentially expressed genes). Of the genes with greater then 2-fold change in expression, 85% were upregulated suggesting that in a physiological setting H2O2predominantly activates gene expression. Pathway analysis identified gene expression signatures associated with FOXO and NTRK signalling. These signatures were associated with an overlapping set of transcriptional regulators. Overall, our results provide a snapshot of gene expression changes in response to H2O2, 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 H2O2signalling.