RRC ID |
46657
|
Author |
Murphy JT, Bruinsma JJ, Schneider DL, Collier S, Guthrie J, Chinwalla A, Robertson JD, Mardis ER, Kornfeld K.
|
Title |
Histidine protects against zinc and nickel toxicity in Caenorhabditis elegans.
|
Journal |
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.
|
Volume |
7(3)
|
Pages |
e1002013
|
Published |
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
|
Times Cited |
27
|
WOS Category
|
GENETICS & HEREDITY
|
Resource |
C.elegans |
tm788 |