Induction Of Metallothionein-like Proteins Research Articles

Uptake and efflux of Cd and Zn by the green mussel Perna viridis after metal preexposure.

Cadmium and zinc uptake from the dissolved phase, assimilation efficiency from the dietary phase, efflux rate constants, and body burden as well as clearance rate were measured in the green mussel Perna viridis with or without laboratory preexposure to Cd or Zn. Efflux rate constants and clearance rates were little affected by preexposure to either Cd or Zn. In contrast, the assimilation of Cd increased by 1.2-1.6 in mussels preexposed to Cd (subsequent Cd concentrations 10.2-25.9 microg(-1)) as compared to controls (0.19-0.39 microg g(-1)). This increase corresponded to an elevation in the proportion of Cd associated with the metallothionein-like proteins (MTLPs) in the mussels, suggesting that exposure to Cd and subsequent induction of MTLPs affected Cd accumulation. Exposure to Zn only resulted in elevated body concentrations following 7-d exposure to 250 microg L(-1), although Zn and Cd uptake from the dissolved phase were reduced by 24-47% by exposure to a lower concentration (100 microg L(-1)) for 7 and 21 d. Despite the lack of an increase in body Zn concentration, the subcellular distribution was altered such that the proportion of Zn associated with the metal-rich granules increased. This study indicates the importance of the subcellular distribution of metals in affecting the biokinetics and thus the toxic effects of metals on aquatic animals. Cd preexposure has potential effects on its influx from the dietary phase, e.g., increasing the importance of dietary uptake and further increasing the body burdens. In contrast, preexposure to Zn has a negative effect on Cd and Zn influx from the dissolved phase, suggesting the mechanism of Zn regulation but also potentially reducing Cd uptake and body concentrations over the long-term exposure. Such effects may have implications for biomonitoring studies involving a single species that modifies physiological processes affecting metal uptake (and hence bioavailability). Caution is needed in extrapolating data to species not capable of making such changes, particularly for Cd, which is not regulated and for which the effects of an elevated body burden are most obvious.

P-537 - Induction of metallothionein like protein in the liver of mice given arsenite

P-537 - Induction of metallothionein like protein in the liver of mice given arsenite

Influence of Cu, Cd, and Zn Preexposure on Hg Toxicity in the Mussel Mytilus edulis

Prior exposure of the marine mussel Mytilus edulis to Cu, Cd, or Zn conferred increased tolerance to the toxicity of inorganic Hg. This acquired tolerance could, in part, be attributed to the apparent induction of metallothionein-like proteins during the preexposure, it appeared that some prior conditions must be satisfied during the preexposure for the enhanced tolerance to be elicited: (1) preexposure had to be sufficiently high that metal bioaccumulation occurred; this presumably initiated cellular compensatory responses; (2) preexposure had to be below levels which could itself become a major component to toxicity. Effective preexposure concentrations fell within this range of concentrations.

Possible biological reference material for environmental control analyses — cadmium induced proteins from Mytilus galloprovincialis

Electrochemical methods have been applied for chemical characterization of metallothionein-like proteins (MLPs) isolated from the digestive gland of Mytilus galloprovincialis, chronically exposed to cadmium. Previous results support the view that the induction of MLPs in the digestive gland of this edible marine organism represents a measurable biological response to the chronic exposure of cadmium and therefore the development of a possible reference material from the digestive gland is proposed.

An evaluation of tissue metallothionein and genetic resistance to cadmium toxicity in mice

The role of metallothionein or metallothionein-like proteins (MT) in genetic resistance to the testicular and hepatic toxicity of cadmium was examined in inbred strains of mice. Mice of two strains resistant (AJ and C3H HEJ ) or susceptible (129J and DBA 2J ) to cadmium-induced testicular necrosis were administered sc 30 μmol CdCl 2/kg. The uptake of cadmium and the induction of MT in tissues were determined after 6 hr. The results showed that accumulation of cadmium in liver and kidney tissues of the four strains was very similar. MT levels were elevated up to 20-fold in the liver and up to almost 8-fold in the kidney, resulting in cadmium to MT molar ratios of 6.7 to 10.0 in the liver and 1.2 to 1.9 in the kidney. The greatest in crease in hepatic MT as well as the cadmium to MT ratio was in the C3H HEJ strain which is susceptible to cadmium-induced hepatotoxicity. Testicular cadmium levels were significantly elevated in the two susceptible strains. The basal levels of MT-like protein in the testis were generally higher than those in the kidney. Although, only the testis of 129J (susceptible) showed an increase in this protein after 6 hr, both susceptible strains injected with cadmium had significantly higher levels of the protein as compared to the resistant strains. The 30,000-Da cadmium-binding protein in AJ and CD-1 (susceptible) mouse strains was found to cross-react with the anti-MT-serum. Necrotic changes were visible in the testes of the susceptible strains as a result of cadmium administration. Immunohistochemically, there were no significant differences in the localization of MT in the liver, kidney or testis among the four strains. MT or an MT-like protein was concentrated mainly in the interstitial tissue of the mouse testis, but was also detected in the seminiferous tubules. It is concluded that the strain differences in acute toxicity of cadmium are probably not due to low MT concentration in tissues of the susceptible strains.

The effects of cadmium on a clonal osteogenetic cell, MC3T3-E1: Inhibition of calcification and induction of metallothionein-like protein by cadmium

To clarify the effects of cadmium (Cd) on bone formation, a clonal osteogenetic cell, MC3T3-E1, was used in the present study. After 24 h of culture, Cd at 1 ppm and above decreased DNA synthesis and alkaline phosphatase activity, but Cd at 1.5 ppm caused no significant decrease in collagen content. The cells treated with Cd (0.03–1.0 ppm) for 24 h showed the dose-dependent effects on metallothionein-like protein synthesis. The marked increase of Cd content unbound to metallothionein (MT)-like protein with cadmium at 1 ppm may be responsible for the toxic effects of cadmium. After 10 days of culture, the accumulation of 45Ca to the cell layer decreased with increasing level of cadmium at 0.03 and 0.1 ppm. The cadmium-treated cell layer showed a weaker reaction to histochemical staining for mineral compared with control culture. This result suggests that Cd inhibits an initial process of calcification.

Induction of metallothionein-like protein in human breast tumor cells

BOT-2 cells, a continuous human breast cell line derived from an infiltrating ductal cell carcinoma, accumulate Cd and Zn in a protein-bound form. The data presented represent the first demonstration in human breast cells of (a) cadmium time and concentration uptake, (b) de novo synthesis of metallothionein-like protein induced by cadmium and zinc, and (c) inhibition of metallothionein-like protein by protein and RNA synthesis inhibitors. The metal binding protein synthesized by BOT-2 cells is similar to the metallothionein-like protein of human milk. This protein appears to be important for the bioavailability of zinc in human infants.