Stability of cadmium resistance and metallothionein levels in vitro and in vivo

Endresen, Liv; Bakka, Arne; Glennås, A; Rugstad, Hans Erik

doi:10.1016/0041-008x(83)90234-x

Cited by 17 publications

(16 citation statements)

References 23 publications

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“…This has also been demonstrated by in vivo studies, in which the murine cells were grown as tumors in athymic nude mice, that is, in the absence of Cd, and then re-exposed them to Cd after plating the tumor cells either in tissue culture flasks or in soft agar (11). This mechanism of preserving the acquired Cd resistance is compatible with the evidence presented by Hildebrand et al (15) …”

Section: Discussionsupporting

confidence: 77%

“…These cells have been used for further studies on Cd metabolism and experiments to reveal functions of the MT. Culture methods and experimental conditions are detailed elsewhere (9)(10)(11)(12) Figure 1 shows the results from experiments with the concentration of cellular Cd much higher than that which after about 8 hr incubation injured the nonresistant cells to a degree not compatible with further growth. The critical level of intracellular Cd which cannot be exceeded without lethal consequences on nonresistant cells seems to be 6-8 nmole/mg cell protein, whereas the resistant cells contained 20-30 nmole/mg after 24 hr growth with CdCl2.…”

Section: Resistance and Mt Levels In Cultured Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Cadmium Uptake and Metabolism in Cultured Cells

Glennås¹,

Rugstad²

1984

Environmental Health Perspectives

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Section: Discussionsupporting

confidence: 77%

Section: Resistance and Mt Levels In Cultured Cellsmentioning

confidence: 99%

Cadmium Uptake and Metabolism in Cultured Cells

Glennås¹,

Rugstad²

1984

Environmental Health Perspectives

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“…Several hypotheses have developed in the last two decades that attempt to explain this phenomenon. One hypothesis suggests that the pretreatment dose acts at the translational level to increase the amount of MT transcript (mRNA) such that further synthesis occurs rapidly and without delay following exposure to the second challenge dose of Cd (Webb, 1972;Cempel and Webb, 1976;Squibb and Cousins, 1977;Endresen et al, 1983). This hypothesis assumes that MT mRNA is already present within the cell and that heavy metals like Cd can transform the mRNA from an inactive to an active form.…”

Section: Introductionmentioning

confidence: 98%

Tolerance to cadmium‐induced toxicity depends on presynthesized metallothionein in liver

Goering

Klaassen

1984

Journal of Toxicology and Environmental Health

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Tolerance to Cd-induced toxicity following pretreatment with Cd is well documented, yet the exact mechanism of tolerance and role of metallothionein (MT) remains equivocal. In this study it was determined if the rapid induction of MT following injection of a challenge dose of Cd or the concentration of presynthesized MT induced by Cd pretreatment is more important for development of tolerance by ascertaining (1) whether the rates of synthesis of MT differ following injection of the challenge dose of Cd in control and Cd-pretreated rats and (2) if a relationship exists between presynthesized hepatic or renal MT and tolerance to Cd-induced lethality. Rates of hepatic and renal MT synthesis did not differ following injection of a challenge dose of Cd (2.0 mg Cd/kg, iv) in control and Cd-pretreated (2.0 mg Cd/kg, sc) rats. However, the progressive increase in concentration of MT in liver after Cd pretreatment correlated with the increase in tolerance to a lethal dose of Cd (4.0 mg Cd/kg, iv), as evidenced by a decrease in mortality in pretreated rats. A similar correlation was not observed between kidney MT levels and tolerance. Therefore, it appears that presynthesized MT in liver rather than increased synthesis of MT following injection of a second dose of Cd is responsible for Cd-induced tolerance.

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“…In addition, restraints for some of the C a C b S c Cd v 2 torsional angles of non-bridging cysteines were obtained from 3 J HbCd coupling constants using the 1 The sequences of the lobster (crab) b N and b C domains of MT-1 and the rabbit MT-2 b N domain are given in Table S1 of the Supplementary material. The Cd-cysteine thiolate connectivities for the lobster and crab domains are identical: Cd 3 b N -Cd II (Cys5, 9,22,25), -Cd III (Cys4, 5,16,20), -Cd V (Cys11, 16,25,27); Cd 3 b CCd I (Cys39,45,49,56), -Cd IV (Cys33,37,55,56); and Cd VI (Cys30, 33,49,53). Those for rabbit MT-2 Cd 3 b N are Cd IV (Cys5,7,21,24), Cd III (Cys7, 13,15,26), Cd II (Cys15, 19,24,29).…”

Section: Distance and Dihedral Angle Restraintsmentioning

confidence: 97%

“…These features confer on MT its well-established, large metal-binding capacity. Among the numerous biological roles attributed to MT are detoxification of heavy metals such as Hg 2+ or Cd 2+ , radical scavenging of reactive oxygen species, metabolism of alkylating agents and other metallodrugs, participation in the stress response and regulation of zinc and copper metabolism including donation of zinc and copper to newly synthesized apoenzymes [2,3,4,5,6,7,8,9,10]. All of these activities are predicated on the metal and ligand substitution properties of the protein as well as the reactivity of its thiol groups [11].…”

Section: Introductionmentioning

confidence: 99%

Structure of the 113Cd3β domains from Homarus americanus metallothionein-1: hydrogen bonding and solvent accessibility of sulfur atoms

et al. 2002

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The three-dimensional structures of the isolated Cd(3)beta domains from Homarus americanus metallothionein have been determined by NMR methods in order to establish a set of beta-domain structures for comparative analysis. First, it was determined that the Cd-cysteine connectivities forming the Cd(3)S(9) metal center were identical to those observed for the beta(N) domain in the native holoprotein. Time- and temperature-dependence studies of the (113)Cd and (1)H 1D-NMR spectra indicated that the beta(N) domain undergoes slow conformational changes before reaching an equilibrium structure. In addition to structural information provided by the metal-to-cysteine connectivities, Phi, chi(1) and chi(2) angle constraints, three H(N...)S hydrogen bond interactions were also determined from a long-range optimized (1)H(N)-(113)Cd HMQC experiment. A simulated annealing protocol was applied to the distance and angle constraints obtained from the 2D-NMR experiments to calculate the three-dimensional structure of the synthetic Cd(3)beta(N) domain of lobster metallothionein. Structure-reactivity relationships are proposed for the reactions of Cd(3)beta domains with 5,5'-dithiobis(2-nitrobenzoate), based on comparisons of surface exposure of sulfur atoms of the lobster and rabbit Cd(3)beta domain structures. Finally, the surface exposure of the beta domains of lobster is compared with beta domains from mammalian metallothioneins.

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Stability of cadmium resistance and metallothionein levels in vitro and in vivo

Cited by 17 publications

References 23 publications

Cadmium Uptake and Metabolism in Cultured Cells

Cadmium Uptake and Metabolism in Cultured Cells

Tolerance to cadmium‐induced toxicity depends on presynthesized metallothionein in liver

Structure of the 113Cd3β domains from Homarus americanus metallothionein-1: hydrogen bonding and solvent accessibility of sulfur atoms

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