RRC ID 46657
著者 Murphy JT, Bruinsma JJ, Schneider DL, Collier S, Guthrie J, Chinwalla A, Robertson JD, Mardis ER, Kornfeld K.
タイトル Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.
ジャーナル PLoS Genet
Abstract Zinc is an essential trace element involved in a wide range of biological processes and human diseases. Zinc excess is deleterious, and animals require mechanisms to protect against zinc toxicity. To identify genes that modulate zinc tolerance, we performed a forward genetic screen for Caenorhabditis elegans mutants that were resistant to zinc toxicity. Here we demonstrate that mutations of the C. elegans histidine ammonia lyase (haly-1) gene promote zinc tolerance. C. elegans haly-1 encodes a protein that is homologous to vertebrate HAL, an enzyme that converts histidine to urocanic acid. haly-1 mutant animals displayed elevated levels of histidine, indicating that C. elegans HALY-1 protein is an enzyme involved in histidine catabolism. These results suggest the model that elevated histidine chelates zinc and thereby reduces zinc toxicity. Supporting this hypothesis, we demonstrated that dietary histidine promotes zinc tolerance. Nickel is another metal that binds histidine with high affinity. We demonstrated that haly-1 mutant animals are resistant to nickel toxicity and dietary histidine promotes nickel tolerance in wild-type animals. These studies identify a novel role for haly-1 and histidine in zinc metabolism and may be relevant for other animals.
巻・号 7(3)
ページ e1002013
公開日 2011-3-1
DOI 10.1371/journal.pgen.1002013
PMID 21455490
PMC PMC3063764
MeSH Animals Caenorhabditis elegans / drug effects* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Gene Order Histidine / metabolism Histidine / pharmacology* Histidine Ammonia-Lyase / chemistry Histidine Ammonia-Lyase / genetics Histidine Ammonia-Lyase / metabolism Mutation Nickel / metabolism Nickel / toxicity* Zinc / metabolism Zinc / toxicity*
IF 5.175
引用数 27
WOS 分野 GENETICS & HEREDITY
リソース情報
線虫 tm788