Journal Article

Chemical Genomic Profiling for Identifying Intracellular Targets of Toxicants Producing Parkinson's Disease

Julie Doostzadeh, Ronald W. Davis, Guri N. Giaever, Corey Nislow and James W. Langston

in Toxicological Sciences

Volume 95, issue 1, pages 182-187
Published in print January 2007 | ISSN: 1096-6080
Published online October 2006 | e-ISSN: 1096-0929 | DOI: https://dx.doi.org/10.1093/toxsci/kfl131
Chemical Genomic Profiling for Identifying Intracellular Targets of Toxicants Producing Parkinson's Disease

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The yeast deletion collection includes ∼4700 strains deleted for both copies of every nonessential gene. This collection is a powerful resource for identifying the cellular pathways that functionally interact with drugs. In the present study, the complete pool of ∼4700 barcoded homozygous deletion strains of Saccharomyces cerevisiae were surveyed to identify genes/pathways interacting with 1-methyl-4-phenylpyridinium (MPP+) and N,N-dimethyl-4-4-bipiridinium (paraquat), neurotoxicants that can produce Parkinson's disease. Each yeast mutant is molecularly “barcoded” the collections can be grown competitively and ranked for sensitivity by microarray hybridization. Analysis data from these screens allowed us to determine that the multivesicular body pathway is an important element of toxicity induced by both MPP+ and paraquat. When yeast genes that when deleted showed sensitivity to MPP+ and paraquat toxicity were analyzed for their homology to human genes, 80% were found to have highly conserved human homologs (with e < 10−8). Future work will address if these human genes may also functionally interact with MPP+ and paraquat toxicity.

Keywords: chemogenomics; neurotoxicants; Parkinson's disease

Journal Article.  2869 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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