| Insights into the mechanisms of toxicity and tolerance to the agricultural fungicide mancozeb in yeast, as suggested by a chemogenomic approach. | |
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MedLine Citation:
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PMID: 20337531 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Abstract Saccharomyces cerevisiae was used to uncover the mechanisms underlying tolerance and toxicity of the agricultural fungicide mancozeb, linked to cancer and Parkinson's disease development. Chemogenomics screening of a yeast deletion mutant collection revealed 286 genes that provide protection against mancozeb toxicity. The most significant Gene Ontology (GO) terms enriched in this dataset are associated to transcriptional machinery, vacuolar organization and biogenesis, intracellular trafficking, and cellular pH regulation. Clustering based on physical and genetic interactions further highlighted the role of oxidative stress response, protein degradation and carbohydrate/energy metabolism in mancozeb stress tolerance. Mancozeb was found to act in yeast as a thiol-reactive compound, but not as a free radical or reative oxygen species (ROS) inducer, leading to massive oxidation of protein cysteins, consistent with the requirement of genes involved in glutathione biosynthesis and reduction and in protein degradation to provide mancozeb resistance. The identification of Botrytis cinerea homologues of yeast mancozeb tolerance determinants is expected to guide studies on mancozeb mechanisms of action and tolerance in phytopathogenic fungi. The generated networks of protein-protein associations of yeast mancozeb tolerance determinants and their human orthologues share a high degree of similarity. This toxicogenomics analysis may, thus, increase the understanding of mancozeb toxicity and adaptation mechanisms in humans. |
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Authors:
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Paulo J Dias; Miguel C Teixeira; Jo?o P Telo; Isabel S?-Correia |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Omics : a journal of integrative biology Volume: 14 ISSN: 1557-8100 ISO Abbreviation: OMICS Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-04-09 Completed Date: 2010-06-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101131135 Medline TA: OMICS Country: United States |
Other Details:
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Languages: eng Pagination: 211-27 Citation Subset: IM |
Affiliation:
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IBB-Institute for Biotechnology and BioEngineering, Centro de Engenharia Biol?gica e Qu?mica, Instituto Superior T?cnico, Lisboa, Portugal. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Drug Resistance, Fungal
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genetics,
physiology Electron Spin Resonance Spectroscopy Fungicides, Industrial / pharmacology* Gene Expression Regulation, Fungal / drug effects, genetics Genome, Fungal / genetics Humans Maneb / pharmacology* Protein Carbonylation / drug effects Reactive Oxygen Species / metabolism Saccharomyces cerevisiae / drug effects*, metabolism* Sulfhydryl Compounds / metabolism Zineb / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Fungicides, Industrial; 0/Reactive Oxygen Species; 0/Sulfhydryl Compounds; 12122-67-7/Zineb; 12427-38-2/Maneb; 8018-01-7/mancozeb |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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