Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of Dictyostelium discoideum treated with mercury - a systems biology assessment of the model eukaryote Dictyostelium discoideum unveils compensatory responses and a critical role of the amino acid metabolic balance in the early phase of mercury induced cyto-toxicity

ABSTRACT: Gene expression alone is not able to characterize the physiological status of pollutant-challenged organisms. However, when transcriptomics is integrated with functional information, it becomes an extremely powerful tool, able to distinguish between compensatory and non-protective cytotoxic responses. Here we present the implementation of a systems biology approach based on transcriptomics, metabolomics, targeted proteomics, and functional cellular tests to assess the global effects of mercury - a diffuse environmental contaminant and a cell poison - on the model eukaryote Dictyostelium discoideum. Two different exposure levels were compared, a sub-lethal condition and the lowest observable lethal dose. DNA microarrays and gene ontology analysis indicated quantitative and qualitative differences in the two changing transcriptomes, with a dose dependent increase of numbers of genes , as well as biological processes involved. The systems approach showed that a co mmon part of this genomic response serves for Hg detoxification, making use of glutathione metabolism and small molecule efflux by ABC transporters: the mRNA and protein levels, as well as cellular functions of components of these systems were raised dose dependently. However, at the higher Hg dose microarrays also indicated the involvement of new GO items whose genes were respectively up- or down-regulated: (i) amino acid metabolism, protein catabolism (the proteasome complex); (ii) DNA metabolism, cell cycle. In analogy, altered levels of ubiquitinated proteins, a severe drop in levels of several amino acids and a dramatic decrease in cell replication rate were found. Despite the huge increase in GSH concentration, in this condition, amoebae start dying. Our data demonstrate a central role of the deregulation of the anabolic/metabolic balance in the early phase of heavy metal cytotoxicity.

ORGANISM(S): Dictyostelium discoideum

SUBMITTER: Gareth Bloomfield

PROVIDER: E-TABM-710 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling of Dictyostelium discoideum treated with mercury - a systems biology assessment of the model eukaryote Dictyostelium discoideum unveils compensatory responses and a critical role of the amino acid metabolic balance in the early phase of mercury induced cyto-toxicity

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