Metallothioneins Are Required for Formation of Cross-Adaptation Response to Neurobehavioral Toxicity from Lead and Mercury Exposure in Nematodes

Abstract

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.

Small sizes of TiO2-NPs exhibit adverse effects at predicted environmental relevant concentrations on nematodes in a modified chronic toxicity assay system

“…Ten replicates were performed. Locomotion behaviors of nematodes were evaluated by head thrash, and body bend [18]. Locomotion behavior was used to assess the neurotoxicity of specific toxicant, because specific toxicants, such as Al 2 O 3 -NPs, exposure suppressed the locomotion behavior by influencing the neurotransmission of nematodes [35].…”

“…A series of endpoints including lethality, development, reproduction, lifespan, neuronal development and function, stress response, and oxidative damage have been developed and applied for environmental toxicity biomonitoring in C. elegans [10][11][12][13][14][15][16][17][18][19]. Recently, C. elegans has been further explored for the toxicity evaluation and toxicological studies of metal oxide NPs or metal NPs such as Al 2 O 3 -NPs, ZnO-NPs, TiO 2 -NPs, and Ag-NPs [20][21][22][23][24][25][26].…”

High Concentration of Vitamin E Decreases Thermosensation and Thermotaxis Learning and the Underlying Mechanisms in the Nematode Caenorhabditis elegans

“…To induce expression of PKC-1, PKC-1 was activated using a heat shock promoter (P hsp-16.2 ) in nematodes [54]. After 400 µg/mL of vitamin E treatment, PKC-1 was activated by heat shock at 30°C for 4-hr.…”

Cross-adaptation to cadmium stress inPlantago ovataby pre-exposure to low dose of gamma rays: Effects on metallothionein and metal content

“…Cadmium, like other abiotic stresses, frequently causes oxidative stress which may leads to DNA damage, alteration in membrane permeability and denaturation of functional and structural proteins (Smirnoff 1998 (Cai et al 1999, Ye et al 2010). It has been reported that in animals, apart from acting as an antioxidant defense protein, metallothionein also impart radio protection when they are exposed to other chemical mutagens.…”