title: The transcriptional response of Caenorhabditis elegans to Ivermectin exposure identifies novel genes involved in the response to reduced food intake.
abstract: We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short-term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms.
authors.affiliation: Faculty of Veterinary Medicine, University of Glasgow, Glasgow, Strathclyde, United Kingdom.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Laing
authors.forename: Al
authors.initials: A
authors.lastname: Ivens
authors.forename: Victoria
authors.initials: V
authors.lastname: Butler
authors.forename: Sai P
authors.initials: SP
authors.lastname: Ravikumar
authors.forename: Roz
authors.initials: R
authors.lastname: Laing
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Woods
authors.forename: John S
authors.initials: JS
authors.lastname: Gilleard
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents; D017173:Caenorhabditis elegans / Q000235:genetics*; D004435:Eating / Q000235:genetics*; D005223:Fats / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D007559:Ivermectin / Q000494:pharmacology*; D053858:Metabolic Networks and Pathways; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000977:Antiparasitic Agents; D005223:Fats; D005227:Fatty Acids; D007559:Ivermectin