|
| Metals | Effects Observed | Reference |
|
| Glutatione |
|
| Arsenic | Nematodes with loss of glutamylcysteine synthetase (gsc-1) demonstrated hypersensitivity to arsenic exposure in lethality testing. Effect was rescued by the addition of GSH to medium. | [34] |
|
| Methylmercury | Significant increase in fluorescence of gst-4::GFP following MeHg exposure. Knockout gst-4 worms not more sensitive than wildtype. GSH levels increased following acute exposure; chronic exposure depleted levels of GSH. GSH found to regulate the hormetic response. | [35] |
|
| Cadmium | Low Cd exposure in phytochelation synthase-1 (pcs-1) RNAi worms resulted in worms that were small, necrotic, sterile, and had a shorter lifespan. Following higher concentrations of Cd, pcs-1 worms arrested at L2–L4 stage were necrotic and died. | [36] |
|
| Cadmium | Primary response to low levels of cadmium is the regulation of the transsulfuration pathway due to decreases in cystathionine concentrations and increases in phytochelation-2 and -3. MT-pcs-1 triple mutants showed added sensitivity. | [37] |
|
| Metallothioneins |
|
| Depleted uranium | Concentration-dependent DU toxicity and protection by MTs. Mtl-1 knockouts displayed increased cellular accumulation of DU. | [12] |
|
| Lead and methylmercury | Pretreatment of larva with heat shock prevented the neurobehavioral deficits and the stress response at lower concentrations (50–100 μM) but not at higher concentrations (200 μM). Mild heat shock and low concentration of either metal found to induce mtl-1 and mtl-2 promoter activity and GFP expression. Overexpression of mtl-1 or mtl-2 at L2 stage significantly repressed neurobehavioral toxicity. | [38] |
|
| Methylmercury | Mtl knockouts displayed increased lethality upon exposure to MeHg. Increases in mtl-1 following acute MeHg exposure at L1 stage but no change following chronic exposure. | [39] |
|
| Silver Nanoparticles | Mtl-2 strain displayed greater AgNP sensitivity than wildtype. Toxicity mediated by ionic silver. | [40] |
|
| Cadmium | MT isoforms found to be independent and not synergistic. Cadmium but not copper or zinc was able to influence a concentration-dependent, temporal transcription response. | [41] |
|
| Cadmium | Metallothionein status did not influence the metabolic profile in cadmium-exposed or -unexposed worms. Primary response was the regulation of the transsulfuration pathway. | [37] |
|
| Zinc and cadmium | Differential metal binding behavior for MT-1 compared to MT-2. MT-1 had optimal behavior when binding Zn, MT-2 optimal behavior when binding Cd. | [42] |
|
| Zinc and cadmium | Zinc levels significantly increased in mtl-1, mtl-2, and double knockouts, mtl-1 knockout worms demonstrating the most acute level of sensitivity. Cd accumulation found to be highest in mtl-2 and double mutant strains. | [43] |
|
| Cadmium and copper | MT-1 mRNA levels significantly higher in daf-2 mutants compared to age-1 mutants and wild-type worms under basal conditions. Cd treatment resulted in 3-fold induction of MT-1 and 2-fold induction of MT-2 mRNA in daf-2 mutants compared to wild-type controls. Copper did not induce expression in any of the strains tested. | [44] |
|
| Pumps and Transporters |
|
| Arsenite and antimonite | ArsA ATPase (asna-1) gene stimulated by As (III) and Sb (III) crucial for establishing tolerance. | [45] |
|
| Arsenite and Cadmium Antimony | Inactivation of mrp-1 rendered As and Cd exposed worms incapable of recovering from temporary exposure to high As and Cd, wildtype worms were able to recover. Worms were hypersensitive to As and Cd exposures when both mrp-1 and pgp-1 were deleted. No increased sensitivity in response to antimony observed in mrp-1 deletion mutants compared to wild types. | [46] |
|
| Cadmium | Suppression of hmt-1 (half-molecule ABC transporter of the heavy metal tolerance family-1) by RNAi shown to produce inclusions within the nucleus of the intestinal epithelial cells upon exposure to toxic levels of Cd. | [47] |
|
| Arsenic, copper, and cadmium | HMT1—conferred tolerance in response to exposure to all three metals revealed through lethality testing following knockdown of hmt-1. | [48] |
|
| Cadmium | Three-fold induction of pgp-5 following Cd exposure. Copper and zinc also found to be capable of inducing pgp-5 expression. Mutant pgp-5 worms showed developmental delay following Cd and Cu exposure. | [49] |
|
| Manganese | Deletion of the three DMT-1-like (divalent-metal transporter) genes resulted in differential effects. smf-1 and -3 increased Mn tolerance, and smf-2 increased Mn sensitivity. | [50] |
|
| Heat Shock Proteins |
|
| Methylmercury | Following 30 minute exposure to acute MeHg, hsp-4 was unaltered. Hsp-4 induced in L4 worms chronically exposed to MeHg for 15 hours. | [39] |
|
| Cadmium and mercury | Cd-inhibited feeding behavior significantly but not completely. Exposure to 1 ppm Cd induced hsp16 genes. Hg also did not entirely inhibit feeding behavior and was shown to inhibit feeding at concentrations similar to those necessary for the induction of a stress response. | [18] |
|
