Metallothioneins are required for formation of cross-adaptation response to neurobehavioral toxicity from lead and mercury exposure in nematodes.
Metallothioneins (MTs) are small, cysteine-rich polypeptides, but the role of MTs in inducing the formation of adaptive response is still largely unknown. We investigated the roles of metallothionein genes (mtl-1 and mtl-2) in the formation of cross-adaptation response to neurobehavioral toxicity from metal exposure in Caenorhabditis elegans. Pre-treatment with mild heat-shock at L2-larva stage effectively prevented the formation of the neurobehavioral defects and the activation of severe stress response in metal exposed nematodes at concentrations of 50 and 100 µM, but pre-treatment with mild heat-shock did not prevent the formation of neurobehavioral defects in 200 µM of metal exposed nematodes. During the formation of cross-adaptation response, the induction of mtl-1 and mtl-2 promoter activity and subsequent GFP gene expression were sharply increased in 50 µM or 100 µM of metal exposed Pmtl-1::GFP and Pmtl-2::GFP transgenic adult animals after mild heat-shock treatment compared with those treated with mild heat-shock or metal exposure alone. Moreover, after pre-treatment with mild heat-shock, no noticeable increase of locomotion behaviors could be observed in metal exposed mtl-1 or mtl-2 mutant nematodes compared to those without mild heat-shock pre-treatment. The defects of adaptive response to neurobehavioral toxicity induced by metal exposure formed in mtl-1 and mtl-2 mutants could be completely rescued by the expression of mtl-1 and mtl-2 with the aid of their native promoters. Furthermore, over-expression of MTL-1 and MTL-2 at the L2-larval stage significantly suppressed the toxicity on locomotion behaviors from metal exposure at all examined concentrations. Therefore, the normal formation of cross-adaptation response to neurobehavioral toxicity induced by metal exposure may need the enough accumulation of MTs protein in animal tissues.
College of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
Boping
B
Ye
Qi
Q
Rui
Qiuli
Q
Wu
Dayong
D
Wang
D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005816:Genetic Complementation Test; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics / Q000502:physiology; D006358:Hot Temperature; D007854:Lead / Q000633:toxicity*; D008627:Mercuric Chloride / Q000633:toxicity*; D008628:Mercury / Q000633:toxicity*; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
D029742:Caenorhabditis elegans Proteins; C557623:MTL-1 protein, C elegans; C557624:MTL-2 protein, C elegans; D049452:Green Fluorescent Proteins; D007854:Lead; D008627:Mercuric Chloride; D008668:Metallothionein; D008628:Mercury