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

Hydrogen peroxide (HO) is a ubiquitous oxidant produced in a regulated manner by various enzymes in mammalian cells. HO reversibly oxidizes thiol groups of cysteine residues to mediate intracellular signaling. While examples of HOdependent 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 HO was investigated to determine global effects on gene expression. With a low HO 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 HO 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 HO which, along with further studies, will lead to new insights into the specific pathways that are activated in response to endogenous production of HO, and the molecular mechanisms of HO signaling.