Research article

Comparison of gene expression signatures of diamide, H₂O₂ and menadione exposed Aspergillus nidulans cultures – linking genome-wide transcriptional changes to cellular physiology

István Pócsi¹ , Márton Miskei¹ , Zsolt Karányi² , Tamás Emri¹ , Patricia Ayoubi³ , Tünde Pusztahelyi¹ , György Balla⁴ and Rolf A Prade⁵

¹Department of Microbiology and Biotechnology, Faculty of Science, University of Debrecen, P.O.Box 63, H-4010 Debrecen, Hungary

²Department of Medicine, Faculty of Medicine, University of Debrecen, P.O. Box 19, H-4012 Debrecen, Hungary

³Department of Biochemistry and Molecular Biology, Oklahoma State University, 348E Noble Research Center, Stillwater, OK 74078, USA

⁴Department of Neonatology, Faculty of Medicine, University of Debrecen, P.O.Box 37; H-4012 Debrecen, Hungary

⁵Department of Microbiology and Molecular Genetics, Oklahoma State University, 307 LSE, Stillwater, OK 74078, USA

author email corresponding author email

BMC Genomics 2005, 6:182doi:10.1186/1471-2164-6-182

Published:	20 December 2005

Abstract

Background

In 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 (O₂^2-), superoxide (O₂^•-) and glutathione/glutathione disulphide (GSH/GSSG) redox imbalance responses.

Results

Genome-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 O₂^2-, 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, O₂^2- 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.

Conclusion

The existence of separate O₂^2-, 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.