RRC ID 46343
Author Schleit J, Wall VZ, Simko M, Kaeberlein M.
Title The MDT-15 subunit of mediator interacts with dietary restriction to modulate longevity and fluoranthene toxicity in Caenorhabditis elegans.
Journal PLoS One
Abstract Dietary restriction (DR), the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA). FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS), which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway.
Volume 6(11)
Pages e28036
Published 2011-1-1
DOI 10.1371/journal.pone.0028036
PII PONE-D-11-12226
PMID 22132200
PMC PMC3221695
MeSH Animals Bacteria / drug effects Caenorhabditis elegans / drug effects Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Caloric Restriction* Cell Nucleus / drug effects Cell Nucleus / metabolism Diet* Drug Resistance / drug effects Fluorenes / chemistry Fluorenes / toxicity* Forkhead Transcription Factors Green Fluorescent Proteins / metabolism Insulin / metabolism Insulin-Like Growth Factor I / metabolism Longevity / drug effects* Mediator Complex / metabolism* Mutation / genetics Pharynx / drug effects Protein Subunits / metabolism Signal Transduction / drug effects Transcription Factors / metabolism*
IF 2.74
Times Cited 6
C.elegans tm2182 tm2183