Abstract
BackgroundIn addition to their cytotoxic nature, reactive oxygen species (ROS) are also signal molecules in diverse cellular processes in eukaryotic organisms. Linking genome-wide transcriptional changes to cellular physiology in oxidative stress-exposed Aspergillus nidulans cultures provides the opportunity to estimate the sizes of peroxide (O22-), superoxide (O2•-) and glutathione/glutathione disulphide (GSH/GSSG) redox imbalance responses.ResultsGenome-wide transcriptional changes triggered by diamide, H2O2 and menadione in A. nidulans vegetative tissues were recorded using DNA microarrays containing 3533 unique PCR-amplified probes. Evaluation of LOESS-normalized data indicated that 2499 gene probes were affected by at least one stress-inducing agent. The stress induced by diamide and H2O2 were pulse-like, with recovery after 1 h exposure time while no recovery was observed with menadione. The distribution of stress-responsive gene probes among major physiological functional categories was approximately the same for each agent. The gene group sizes solely responsive to changes in intracellular O22-, O2•- concentrations or to GSH/GSSG redox imbalance were estimated at 7.7, 32.6 and 13.0 %, respectively. Gene groups responsive to diamide, H2O2 and menadione treatments and gene groups influenced by GSH/GSSG, O22- and O2•- were only partly overlapping with distinct enrichment profiles within functional categories. Changes in the GSH/GSSG redox state influenced expression of genes coding for PBS2 like MAPK kinase homologue, PSK2 kinase homologue, AtfA transcription factor, and many elements of ubiquitin tagging, cell division cycle regulators, translation machinery proteins, defense and stress proteins, transport proteins as well as many enzymes of the primary and secondary metabolisms. Meanwhile, a separate set of genes encoding transport proteins, CpcA and JlbA amino acid starvation-responsive transcription factors, and some elements of sexual development and sporulation was ROS responsive.ConclusionThe existence of separate O22-, O2•- and GSH/GSSG responsive gene groups in a eukaryotic genome has been demonstrated. Oxidant-triggered, genome-wide transcriptional changes should be analyzed considering changes in oxidative stress-responsive physiological conditions and not correlating them directly to the chemistry and concentrations of the oxidative stress-inducing agent.
Highlights
In addition to their cytotoxic nature, reactive oxygen species (ROS) are signal molecules in diverse cellular processes in eukaryotic organisms
Taking into consideration the high frequency of fluctuating gene expression patterns we considered only transcriptional changes above or below the [+1;-1] M' thresholds as a function of incubation time during gene function analysis (Figure 6, Additional file 2:Supplement2 for the list of oxidative stress responsive gene probes, Additional file 3:Supplement3 for the list of gene probes considered in significant enrichment calculations, Additional file 5:Supplement5 for a selection of GSH/GSSG responsive genes, Additional file 6:Supplement6 for a selection of ROS responsive genes)
Large and separate ROS (O22, O2-) and GSH/GSSG redox groups of genes are present in the A. nidulans genome
Summary
In addition to their cytotoxic nature, reactive oxygen species (ROS) are signal molecules in diverse cellular processes in eukaryotic organisms. Linking genome-wide transcriptional changes to cellular physiology in oxidative stress-exposed Aspergillus nidulans cultures provides the opportunity to estimate the sizes of peroxide (O22-), superoxide (O2-) and glutathione/glutathione disulphide (GSH/GSSG) redox imbalance responses. There is experimental evidence that formation of oxidants is regulated in cells by factors, affecting targets [1,2,3,4]. Different oxidative stress-inducing agents (cumene hydroperoxide, diamide, H2O2, linoleic acid 13hydroperoxide, menadione), which disturb intracellular oxidant concentrations influence segments of the genome differentially with almost no overlap in Saccharomyces cerevisiae, when a genome-wide set of deletion strains was tested [5]. Overdosing with reactants decreases specificity of treatments by increasing the number of affected oxidants and diminishing survival rates [6,7].
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