Suchergebnisse

Metals are important components of living organisms since many biological functions critically depend on their interaction with some meta l in the cell. However, human activities have increased toxic metal levels in the terrestrial and aquatic ecosystems affecting living organisms. The impact of metals on cellular metabolism and global homeostasis has been traditionally assessed in free-living organisms by using conventional biomarkers; however, to obtain a global vision of metal toxicity mechanisms and the res ponses that metals elicit in the organisms, new analytical methodologies are needed. We re view the use of omics approaches to assess the response of living organisms under metal stress illustrating the possibilities of different methodologies on the basis of our previous re sults. Most of this research has been based on free-living mice Mus spretus , a conventional bioindicator used to monitor metal pollution in Doñana National Park (DNP) (SW Spain), which is a n important European biological reserve for migrating birds affected by agricu ltural, mining and industrial ac tivities. The benefits of using omic techniques such as heterologous microarrays, proteomics methodologies (2-DE, iTRAQ®), metallomics, ionomics or metabolomics has been remarked; however, the complexity of these areas requires the integration of omics to achieve a comprehensive assessment of their environmental status. This article is part of a Speci al Issue entitled: Enviro nmental and structural proteomics. Biological Significance This work presents new contributions in the study of environmental metal pollution in terrestrial ecosystems using Mus spretus mi ce as bioindicator in Doñana National Park ; This work was supported by the project CTM2012-38720-C03-01 from the Spanish Ministry of Economy and Competitiveness, and by projects P08-FQM-3554, P09-FQM-4659, P08-CVI-03829, and P08-RNM-00523 from the Regional Ministry of Economy, Innovation, Science and Employment (Andalusian Government, Spain). M.A. Garcia Sevillano thanks the Ministerio de Educacion (Spain) for a PhD scholarship.

Cadmium (Cd) is an environmental pollutant that accumulates in the organisms causing serious health problems. Over the past decades, omics studies have been conducted trying to elucidate changes in the genome, the transcriptome or the proteome after Cd exposure. Metabolomics is relatively new to the omics revolution, but has shown enormous potential for investigating biological systems or their perturbations. When metabolomic data are interpreted in combination with genomic, transcriptomic and proteomic results, in the so-called systems biology approach, a holistic knowledge of the organism/process under investigation can be achieved. In this work, transcriptional and proteomic analysis (functional genomics) were combined with metabolomic workflow to evaluate the biological responses caused in Mus musculus mice by Cd (subcutaneous injection for 10 consecutive days). Animals showed high Cd levels in liver and plasma, drastic lipid peroxidation in liver, increased transcription of hepatic genes involved in oxidative stress, metal transport, immune response and lipid metabolism and moderate decreases of DNA repair genes mRNAs. 2DE-DIGE proteomics confirmed changes of hepatic proteins related to stress and immune responses, or involved in energy metabolism, suggesting a metabolic switch in the liver from oxidative phosphorylation to aerobic glycolysis, that was confirmed by metabolomics analysis, via DIMS and GC–MS. This metabolic alteration is particularly important for highly proliferating cells, like tumor cells, which requires a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. The metabolic changes observed in mouse liver by metabolomics and the oxidative stress detected via functional genomics could be in the base of Cd hepatocarcinogenicity. ; This project received Grants CTM2012-38720-C03-01 and CTM2012-38720-C03-02 from the Ministerio de Economia y Competitividad-Spain; BIO1675, P12-FQM-00442 and P09-FQM-04659 from the Consejeria de Innovacion, Andalusian government. M. A. Garcia-Sevillano thanks to Ministerio de Educacion for a predoctoral grant.