title: Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.
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.
authors: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
authors: John T
authors: JT
authors: Murphy
authors: Janelle J
authors: JJ
authors: Bruinsma
authors: Daniel L
authors: DL
authors: Schneider
authors: Sara
authors: S
authors: Collier
authors: James
authors: J
authors: Guthrie
authors: Asif
authors: A
authors: Chinwalla
authors: J David
authors: JD
authors: Robertson
authors: Elaine R
authors: ER
authors: Mardis
authors: Kerry
authors: K
authors: Kornfeld
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D023061:Gene Order; D006639:Histidine / Q000378:metabolism / Q000494:pharmacology*; D006638:Histidine Ammonia-Lyase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009532:Nickel / Q000378:metabolism / Q000633:toxicity*; D015032:Zinc / Q000378:metabolism / Q000633:toxicity*
chemical_list: D029742:Caenorhabditis elegans Proteins; D006639:Histidine; D009532:Nickel; D006638:Histidine Ammonia-Lyase; D015032:Zinc