Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium

George C T Jiang, Sam Hughes, Stephen R. Stürzenbaum, Lars Evje, Tore Syversen, Michael Aschner

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)345-354
Number of pages10
JournalToxicological Sciences
Volume111
Issue number2
DOIs
StatePublished - 2009
Externally publishedYes

Fingerprint

Uranium
Metallothionein
Caenorhabditis elegans
Toxicity
Radiation shielding
Ammunition
Detoxification
Armor
Transcription
Heavy Metals
Green Fluorescent Proteins
Sulfhydryl Compounds
Gene expression
Reverse Transcription
Protein Isoforms
Proteins
Metals
Health
Radiation

Keywords

  • C. elegans
  • Depleted uranium
  • GFP
  • Knockout
  • Metallothionein
  • Neurotoxicity
  • TaqMan

ASJC Scopus subject areas

  • Toxicology

Cite this

Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium. / Jiang, George C T; Hughes, Sam; Stürzenbaum, Stephen R.; Evje, Lars; Syversen, Tore; Aschner, Michael.

In: Toxicological Sciences, Vol. 111, No. 2, 2009, p. 345-354.

Research output: Contribution to journalArticle

Jiang, George C T ; Hughes, Sam ; Stürzenbaum, Stephen R. ; Evje, Lars ; Syversen, Tore ; Aschner, Michael. / Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium. In: Toxicological Sciences. 2009 ; Vol. 111, No. 2. pp. 345-354.
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