TY - JOUR
T1 - Caenorhabditis elegans metallothioneins protect against toxicity induced by depleted uranium
AU - Jiang, George C.T.
AU - Hughes, Sam
AU - Stürzenbaum, Stephen R.
AU - Evje, Lars
AU - Syversen, Tore
AU - Aschner, Michael
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - C. elegans
KW - Depleted uranium
KW - GFP
KW - Knockout
KW - Metallothionein
KW - Neurotoxicity
KW - TaqMan
UR - http://www.scopus.com/inward/record.url?scp=70349269508&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349269508&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfp161
DO - 10.1093/toxsci/kfp161
M3 - Article
C2 - 19617453
AN - SCOPUS:70349269508
SN - 1096-6080
VL - 111
SP - 345
EP - 354
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 2
ER -