title: Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium.
abstract: Depleted uranium (DU) is a dense and heavy metal used in armor, ammunition, radiation shielding, and counterbalances. The military usage has led to growing public concern regarding the health effects of DU. In this study, we used the nematode, Caenorhabditis elegans, to evaluate the toxicity of DU and its effects in knockout strains of metallothioneins (MTs), which are small thiol-rich proteins that have numerous functions, such as metal sequestration, transport, and detoxification. We examined nematode viability, the accumulation of uranium, changes in MT gene expression by quantitative reverse transcription-PCR, and the induction of green fluorescent protein under the control of the MT promoters, following exposure to DU. Our results indicate that (1) DU causes toxicity in a dose-dependent manner; (2) MTs are protective against DU exposure; and (3) nematode death by DU is not solely a reflection of intracellular uranium concentration. (4) Furthermore, only one of the isoforms of MTs, metallothionein-1 (mtl-1), appears to be important for uranium accumulation in C. elegans. These findings suggest that these highly homologous proteins may have subtle functional differences and indicate that MTs mediate the response to DU.
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
authors.forename: George C-T
authors.initials: GC
authors.lastname: Jiang
authors.forename: Sam
authors.initials: S
authors.lastname: Hughes
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Stürzenbaum
authors.forename: Lars
authors.initials: L
authors.lastname: Evje
authors.forename: Tore
authors.initials: T
authors.lastname: Syversen
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D017931:DNA Primers; D055786:Gene Knockout Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D013058:Mass Spectrometry; D008668:Metallothionein / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014501:Uranium / Q000633:toxicity*
chemical_list: D017931:DNA Primers; D049452:Green Fluorescent Proteins; D014501:Uranium; D008668:Metallothionein