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Biomedical subjects

M Nordberg

Publications and source records attributed to M Nordberg.

At least 127 records · Page 7Linked to original sources
PubMed1986

Characterization studies on the cadmium-binding proteins from two species of New Zealand oysters.

Two different types of New Zealand oysters--Ostrea lutaria (OL) and Crassostrea glomerata (CG)--contained different concentrations of zinc, copper, and cadmium. OL oysters had 5.3 micrograms Cd/g, 3.4 micrograms Cu/g, 100 micrograms Zn/g; CG oysters had 1.4 micrograms Cd/g and 936 micrograms Zn/g. Both kinds of oysters were shown by gel filtration (G-75) to contain cadmium and zinc in fractions corresponding to a high molecular weight protein (corresponding to the size of albumin or larger) which was heat labile. OL oysters contained cadmium in fractions corresponding to a molecular weight of approximately 6500. The cadmium-binding protein in these fractions was heat-stable. This protein contained no detectable amounts of zinc and was not present in the CG oysters. Further purification by gel filtration (G-50) was performed to obtain a purer protein fraction. Isoelectric focusing of the protein obtained by G-50 filtration showed one main fraction of protein with a pI approximately 5.9 at approximately 13 degrees C. CG oysters contained cadmium and zinc in a polypeptide with low molecular weight (MW 1000). The cadmium-binding oyster proteins are minimally reactive in a competitive binding radioimmunoassay in comparison to the reactivity of a typical vertebrate metallothionein; the proteins may be metallothioneins, but, if so, they do not exhibit the principal determinants characteristic of vertebrate metallothioneins.

Animals↗
PubMed1984

General aspects of cadmium: transport, uptake and metabolism by the kidney.

Cadmium taken up from lung and gastrointestinal tract is transported via blood to liver and kidney. On long-term exposure to cadmium, renal tubular dysfunction develops in humans and experimental animals. Data from animal experiments demonstrate that initially after exposure cadmium in blood is bound to albumin and proteins with higher molecular weight. Such cadmium is mainly taken up in liver. For a few days after exposure cadmium exists as metallothionein in plasma and blood cells. After both single and long-term administration of cadmium bound to metallothionein, cadmium is taken up by the kidney. The concentration of metallothionein-bound cadmium in plasma is quite low due to continuous renal clearance. Cadmium from metallothionein is taken up in renal tubules by pinocytosis and subsequently degraded in lysosomes, thereby releasing cadmium which stimulates de novo synthesis of metallothionein but also binds to reabsorbed metallothionein. Catabolizing and rebinding are continuous and prevent excretion of cadmium. Because of differences in transport, renal metabolic handling forms of cadmium are also different for different forms of cadmium administered and rate of administration. A single dose of metallothionein-bound cadmium given intravenously is almost immediately and completely taken up in the renal tubule. Under such conditions, resynthesis and rebinding processes are insufficient to sequester cadmium from sensitive tissue receptors, and renal damage occurs at total tissue concentrations much lower than when renal cadmium concentrations rise slowly. This explains the wide range (10-200 micrograms Cd/g wet weight) of cadmium in the renal cortex that associated with renal tubular dysfunction in experimental animals.

Animals↗
PubMed1984

Metallothionein in rabbit kidneys preserved for transplantation.

Thirteen rabbits were given repeated cadmium injections to achieve cadmium concentrations in kidney cortex ranging from 0.05 to 1 mmole Cd/kg wet weight. Another four animals served as controls. One kidney from each animal was frozen directly to -70 degrees C whereas the other kidney was kept for 24 hr at +4 degrees C in a preservative (Sachs' solution) to simulate conditions for preservation of human donor kidneys before transplantation. Protein binding of cadmium, zinc and copper in kidney homogenates and the concentration of metallothionein (MT) were measured in the kidney that was frozen directly and in the kidney that had been preserved. No gross differences in either the protein binding of cadmium, zinc and copper or in the MT content were seen between the directly frozen and preserved kidneys from the same animal. This indicates that MT is not rapidly broken down in rabbit kidneys which have been preserved similarly to human donor kidneys for 24 hr in a standard preservative solution prior to a transplantation.

Animals↗
PubMed1984

Holiday buying.

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Holidays↗
PubMed1983

Comparison of tissue distribution of cadmium in mice intravenously injected with metallothionein and a polymer of metallothionein.

Polymers of cadmium metallothionein I and II were prepared and used for distribution studies. Mice were intravenously injected with comparable doses of cadmium as chloride, metallothionein and metallothionein-polymer and were killed at 3 h and 24 h after injection. A considerably higher concentration of cadmium was found in the plasma and spleen of animals exposed to metallothionein-polymer than other groups, while the cadmium concentration in the kidney was less than, but in the liver was greater than those injected with cadmium-metallothionein. Gel filtration of liver and kidney cytosols showed that metallothionein is the most stable form of cadmium in the tissues. The injected polymer was degraded into the monomer within 24 h in tissues. The high concentration of polymer in plasma indicates a slow clearance of cadmium in this form. The increased antigenicity of metallothionein-polymer may be related to its slow clearance from blood and increased deposition in spleen.

Animals↗
PubMed1983

Cellular adaptation in metal toxicology and metallothionein.

The cellular adaptation to toxicity of metals is one of the important factors in the evaluation of health effects of increased exposure to metals. Two major types of cellular effects can be distinguished during divalent metal exposure. Some of the experimental evidences on the role of these processes in the cellular toxicity of metals are reviewed in this article. Both these cellular effects are somewhat specific to certain metals and involve two distinct types of protein binding. One of these processes can be considered as a nuclear process, involving binding of metals to nuclear proteins and also the formation of morphologically distinct inclusion bodies. A number of metals such as lead, bismuth, mercury, copper and aluminium are accumulated intranuclearly and bind with non-histone protein in the nuclei. In addition, morphologically distinct intranuclear inclusion bodies are formed in the kidneys of experimental animals and in humans on continuous exposure to lead or bismuth salts. Another cellular effect of divalent metals is a cytoplasmic process involving a specific metal binding protein, metallothionein. This is a unique metalloprotein containing 2 types of metal clusters and its synthesis is induced by both essential (Zn2+ and Cu2+) and non-essential (Cd2+ and Hg2+) metals. A hypothetical model for metal induced synthesis of metallothionein is postulated and is partly based on the recent immunohistochemical localization of metallothionein in the nucleus and cytoplasm of both hepatic and renal cells.

Adaptation, Physiological↗
PubMed1981

Beta 2-microglobulin levels in serum and urine of cadmium exposed rabbits.

Male rabbits were exposed to cadmium during 16 weeks by subcutaneous injections of either 0.25 mg or 0.5 md Cd as cadmium chloride per kg body weight 3 times per week. beta 2-microglobulin (beta 2-m) and creatinine in serum, cadmium in blood, as well as total protein, creatinine, beta 2-m and cadmium in urine were determined before exposure and after 3 and 7 weeks of exposure. Measurements were also made at 19 weeks, 3 weeks after the last exposure. During exposure, there was a slight increase in the serum beta 2-m/creatinine ratio among rabbits with the highest exposure, while no effect of the cadmium burden could be observed once exposure had ceased. Urinary excretion of beta 2-m was related to urinary pH, which appeared to be the case also for excretion of total protein. In the high exposure group, a significant increase in urinary beta 2-m excretion, indicative of renal tubular dysfunction was seen after 7 weeks of exposure. This was, however, not related to serum beta 2-m levels. It was concluded that before renal damage has occurred even heavy cadmium exposure has very little influence on serum beta 2-m levels.

Animals↗
PubMed1975

Distribution of metallothionein-bound cadmium and cadmium chloride in mice: preliminary studies.

Metallothionein from livers of mice was isolated by gel chromatography and isoelectric focusing. One of two forms thus obtained contained 32 percent cysteine. This form, labeled in vitro with 109Cd, was injected intravenously in mice, and the distribution of 109Cd was studied. Animals killed after 4 hrs had over 80 percent of the injected dose in the kidneys. Protein obtained after gel chromatography, containing both forms of cadmium-binding protein, was also labeled in vitro with 109Cd and injected intravenously. Animals killed 4 hrs after injection had 50 percent of the injected dose in the kidneys. Whole-body measurements and wholebody autoradiography demonstrated that approximately 40-60 percent of the injected dose had been excreted in urine. The results show a selective accumulation of metallothionein-bound cadmium in the kidney and indicate possible differences in distribution and excretion of cadmium depending on binding to different forms of low molecular weight cadmium-binding proteins.

Animals↗
PubMed1975

Placental transfer of cadmium in rats: influence of dose and gestational age.

Placental transfer rates of cadmium were investigated in rats in relation to dose (0.1, 0.4, and 1.6 mg Cd/kg) and the gestational age (12, 15, and 20 days) when rats were treated. Pregnant rats were injected intravenously with a single dose of 109CdCl2 (approximately 20 muCi/animal), and animals were sacrificed after 24 hr. 109Cd concentrations were measured in the fetus, placenta, maternal liver, and blood. Cadmium crossed the placenta at all doses and at all gestational ages tested. However, higher percentages of administered cadmium accumulated in the fetus with increasing dose and increasing gestational age. For example, after pregnant rats were injected with low, middle, and high doses of Cd on day 12 of gestation, fetuses accumulated 0.0001, 0.0028, and 0.0095 per cent of the injected dose, respectively. Percentages of administered Cd detected in placental tissue did not change consistently with dose but Cd levels did increase with gestational age. Placental to maternal blood Cd concentration ratios increased with gestational age but not with dose. Maternal liver to fetal liver concentration ratios were 295, 137, and 27 for low, middle and high doses, respectively, 24 hr after pregnant rats were treated on day 20 of gestation. These results are discussed in relation to placental damage, metallothionein inducibility, and fetotoxicity.

Animals↗
PubMed1975

Comparative toxicity of cadmium-metallothionein and cadmium chloride on mouse kidney.

Cadmium-induced metallothionein may have a paradoxical role in the pathogenesis of cadmium toxicity. Mice are protected from cadmium-induced testicular necrosis by metallothionein, but in this experiment it was shown that cadmium-metallothionein complex injected into mice results in higher cadmium levels in renal cortex and more severe renal tubular cell injury than a comparable dose of cadmium chloride administered by the same route. Also, an injection of 1.1 mg/kg of body weight or more of cadmium bound to metallothionein was fatal to male CGA mice within seven days whereas five times this dose of cadmium administered as cadmium chloride was needed to produce a similar effect. A reason for the difference in renal effects of these two forms of cadmium has not been determined but may be related to differences in absorption or transport by renal tubular lining cells.

Animals↗
PubMed1975

Isolation and characterization of a hepatic metallothionein from mice.

Mice were given cadmium chloride orally for 18 weeks, after which they were given two subcutaneous injections of cadmium chloride. Cadmium-and zinc-containing proteins were obtained from livers by ultracentrifugation, Sephadex chromatography and isoelectric focusing. Metallothionein with apI of 4.2 at 8 degrees C was separated from other proteins (possibly including other forms of metallothionein) by the isoelectric procedure. The metallothionein with pI = 4.2 had a high E250, reflecting abundant Cd-SH bonds, in accord with amino acid analysis, which gave a cysteine content of 34.6 residues % and showed an absence of aromatic amino acids. These results indicated a very high purity of the form of metallothionein isolated after isoelectric focusing.

Amino Acids↗
PubMed1972

Separation of two forms of rabbit metallothionein by isoelectric focusing.

Rabbits were given repeated injections of cadmium chloride. Cadmium- and zinc-containing protein fractions were obtained from the livers of these animals by precipitation procedures and Sephadex G-75 chromatography. The protein thus obtained showed several characteristics similar to those of the earlier described protein metallothionein. Further separation by isoelectric focusing showed two main protein peaks with isoelectric points at 3.9 and 4.5 respectively. Amino acid analysis of these two forms showed similar content of most amino acids [residues per cent.: cysteine (28%), aspartate (8%), threonine (5-6%), serine (12%), glycine (7%), alanine (13%), methionine (2%), isoleucine (2%)] but with a small difference in content of lysine (12 and 13% respectively), proline (9 and 5% respectively) and glutamate (2 and 4% respectively). The two forms of the protein both contained cadmium, but only the one with pI4.5 contained also significant amounts of zinc.

Amino Acids↗