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Biomedical subjects

I Bremner

Publications and source records attributed to I Bremner.

At least 55 records · Page 3Linked to original sources
PubMed1987

Stimulation of peroxidation in rat liver microsomes by (copper, zinc)-metallothioneins.

The abilities of pig liver (copper, zinc) metallothionein I and rat liver zinc metallothionein II to modify lipid peroxidation in incubations of liver microsomes have been compared with the activities of reduced glutathione, mannitol, quinacrine, EDTA, dimethyl-pyrroline-N-oxide and phenyl-butyl-nitrone. Lipid peroxidation was determined by assay of thiobarbituric acid reactive substance formation in incubations of microsomes with iron/ADP or a mixture of xanthine and xanthine oxidase. Zinc metallothionein II had no effect on the extent of peroxidation in either system but (copper, zinc) metallothionein I caused a stimulation of peroxidation initiated by xanthine and xanthine oxidase, all other compounds tested were inhibitory. Gel exclusion chromatography of incubations of (copper, zinc) metallothionein I with xanthine and xanthine oxidase revealed aggregation of the metalloprotein. This may have exposed copper in a form capable of initiating peroxidation.

Animals↗
PubMed1987

Interactions between metallothionein and trace elements.

Metallothionein is an important metal-binding protein which occurs in varying amounts in a wide range of tissues but particularly in liver, kidneys, intestine and pancreas. Synthesis of the protein is induced by zinc and copper and also by cadmium and many other non-essential elements. The concentration of the protein in tissues depend on zinc and copper status and on patho-physiological state. A variety of stress factors stimulate metallothionein synthesis, particularly in liver. The turnover rate of metallothionein in tissues is relatively high but depends to a large extent on its metal content. There has been much speculation as to the function of the protein and one important role appears to lie in the cellular detoxification of copper, zinc and other metals. Metallothionein also appears to participate in metabolic interactions between zinc and copper. The protein occurs in small amounts in blood and urine and assay of these concentrations may be used in the assessment of trace element status.

Amino Acid Sequence↗
PubMed1986

Structural study of the copper and zinc sites in metallothioneins by using extended X-ray-absorption fine structure.

Zn-metallothionein 1 from rabbit liver was investigated by means of Zn K-edge extended X-ray-absorption fine structure (e.x.a.f.s.). Also, the Cu and Zn K-edge e.x.a.f.s. were measured for two samples of mixed Cu Zn-metallothionein 2, with Cu/Zn ratios of 5:2 and 6:3, from pig liver. Detailed simulation of the Cu sites shows a primary co-ordination with three sulphur atoms, presumably from cysteine residues at 0.225 nm +/- 0.001 nm (2.25 +/- 0.01 A). The data for the Zn sites are best reproduced by four Zn-S separations at 0.233 +/- 0.001 nm (2.33 +/- 0.01 A). The Zn K-edge e.x.a.f.s. recorded for rabbit metallothionein 1 at 77 K shows, in addition to the primary co-ordination shell, evidence for two Zn-Zn separations at approx. 0.50 nm (5.0 A). This latter result provides the first information concerning the internal arrangement of zinc atoms in Zn7-metallothionein.

Animals↗
PubMed1986

Effects of dietary copper supplementation of rats on the occurrence of metallothionein-I in liver and its secretion into blood, bile and urine.

The appearance and excretion of metallothionein-I (MT-I) was studied in rats given a diet containing 1000 mg of Cu/kg for several weeks. No significant increase in MT-I concentrations in liver, plasma or bile was detected in rats with liver copper concentrations less than 600 micrograms of Cu/g fresh wt. Above this concentration, liver MT-I concentrations increased in proportion to the increase in hepatic copper content. Plasma and bile MT-I concentrations were directly related to those in the liver and were about 10 times those in normal rats. Urinary MT-I concentration also increased 10-fold within 1 week. Fractionation of bile and urine on Sephadex G-50 revealed the presence of monomeric MT-I and a range of possible degradation products of the isoprotein.

Animals↗
PubMed1985

Studies on the metabolism of rat liver copper-metallothionein.

The degradation of purified 35S-labelled rat liver isometallothioneins (MT) by lysosomal extracts was studied. Zn-MT-I was more readily hydrolysed than Zn-MT-II, but no significant degradation of the Cu-containing metallothioneins could be detected, even after 24 h incubation. The susceptibility of MT to degradation in vitro may be related to the strength of the metal-thiolate bonds. However, the turnover rates of cytosolic MT in vivo, as established by pulse-labelling techniques, are apparently subject to different controls. The half-lives of MT-I and -II in the liver cytosol of Cu2+-injected rats were only 15.4 +/- 1.5 and 18.2 +/- 1.1 h respectively. Approx. 25% of the total liver MT was present in particulate fractions (probably in lysosomes) of the liver and had a half-life of 25.1 +/- 4.1 h.

Animals↗
PubMed1985

Observations on the pancreas of cattle deficient in copper.

Lesions were found in the pancreas of clinically normal cattle of low copper status. In comparison with the pancreas of cattle with normal hepatic copper reserves, the abnormalities were an increase in the dry matter content and reduction in the concentrations of protein and copper in the wet tissue. Cytochrome oxidase activity and protein-to-RNA ratio were also reduced. Histologically, there were defects in acinar basement membranes, splitting and disorganization of acini, cellular atrophy and dissociation, and stromal proliferation. The pancreatic ductular system did not show atrophy or disorganization.

Animals↗
PubMed1984

Biliary excretion of metallothionein and a possible degradation product in rats injected with copper and zinc.

The concentrations of metallothionein-I (MT-I) and related immunoreactive products in bile from adult female rats were measured by radioimmunoassay. Concentrations in normal animals were 20-30 ng/ml, but increased to 600 and 75 ng/ml after injection of Cu2+ and Zn2+ respectively (3 mg of metal/kg body wt.). However, only 1-2% of the biliary Cu was bound to MT, and less than 1% of the total liver MT in control or Cu2+-injected rats appeared to be secreted in intact form into bile. Other major immunoreactive components in bile from Cu2+-injected rats included an aggregated form of MT-I and a possible degradation product of the isoprotein.

Animals↗
PubMed1984

Species differences in the occurrence of copper-metallothionein in the particulate fractions of the liver of copper-loaded animals.

Large amounts of Cu-metallothionein were obtained by 2-mercaptoethanol and sodium dodecyl sulphate extractions of the particulate fractions of the liver of pigs given high-Cu2+ diets or rats injected with Cu2+. Three isoproteins were purified from pig liver and characterized on the basis of their physicochemical properties, metal content and amino acid composition. No such pool of Cu-metallothionein was present in the liver of Cu2+-loaded sheep or of rats given Cu2+-supplemented diets.

Amino Acids↗
PubMed1984

Metallothionein-I in the plasma and liver of neonatal rats.

The concentrations of metallothionein-I in the plasma and liver of neonatal rats were measured by radioimmunoassay. Plasma concentrations of the protein in male and female 4-day-old rats were 350 and 740 ng/ml respectively, and declined rapidly to only 3.5 ng/ml at 32 days of age. Concentrations in liver were also high in the newborn rats (200 micrograms/g), and declined from 12 days of age onwards.

Animals↗
PubMed1984

Measurement of plasma metallothionein-I in the assessment of the zinc status of zinc-deficient and stressed rats.

These studies were designed to investigate the effects of stress and of changes in zinc status on plasma and liver concentrations of metallothionein-I (MT-I) in rats and to assess the value of plasma MT-I assays in the diagnosis of zinc deficiency. No MT-I was detected by radioimmunoassay in the plasma or liver of rats made hypozincaemic by feeding diets with less than 1 or 3 mg Zn/kg. Injection of normal rats with endotoxin or CCl4 also decreased plasma zinc levels, but these treatments greatly increased MT-I concentrations in both liver and plasma. Moreover plasma MT-I levels in zinc-deprived rats given endotoxin were only slightly greater than those in untreated rats of normal zinc status. Neither plasma zinc nor MT-I levels were altered in starved rats despite increased levels of the protein in the liver, although a slight increase in plasma MT-I was found in rats pair-fed with zinc-deficient animals. It appears therefore that reduced plasma levels of both zinc and MT-I are indicative of a zinc deficiency state and that assay of plasma MT should be of value in the diagnosis of zinc deficiency.

Animals↗
PubMed1983

Development of a radioimmunoassay for rat liver metallothionein-I and its application to the analysis of rat plasma and kidneys.

A sensitive radioimmunoassay for rat liver metallothionein-I has been developed using avid and high-titre antibodies obtained from sheep that were immunized with a conjugate of metallothionein and rabbit immunoglobulin G. The assay was specific for metallothionein-I, and did not depend on the particular metal bound to the protein. There was no significant cross-reaction with rat liver metallothionein-II. The use of the assay to measure metallothionein concentrations in rat plasma and kidneys is described.

Animals↗
PubMed1983

Thiomolybdates in rumen contents and rumen cultures.

Examination of direct and (Cu)-difference spectra of i) the aqueous supernatants of in vitro cultures of bovine rumen contents incubated with MoO42- and potential sources of S2- and ii) samples drawn directly from the rumen of animals receiving high Mo diets yielded evidence of the presence of thiomolybdates. Only MoS42- was detected in the soluble phase of in vitro cultures. Although intense and variable background absorbance precluded full characterization of thiomolybdate species in samples drawn directly from the rumen, both spectral data and the biochemical and clinical responses of animals given high Mo diets were consistent with the conclusion that MoS42- rather than MoOS32- was the predominant thiomolybdate species present in the aqueous phase. Addition of Ca2+ either to rumen cultures before incubation or as a supplement to diets high in MoO42- content inhibited the appearance of MoS42- in the aqueous phase. Evidence of the sequestration of MoS42- and MoOS32- by particulate or microbial fractions of rumen contents is considered in relation to the inhibitory action of Mo upon Cu absorption by ruminants.

Animals↗
PubMed1983

The influence of dietary iron and molybdenum on copper metabolism in calves.

1. Twenty heifer calves were allocated to four groups and maintained for 32 weeks on a diet based mainly on barley and straw and containing 4 mg copper/kg. The diet was supplemented with 0 or 800 mg iron/kg and 0 or 5 mg molybdenum/kg. 2. Liver and plasma Cu concentrations, erythrocyte superoxide dismutase (EC 1.15.1.1) and plasma caeruloplasmin (EC 1.16.3.1) activities decreased greatly and rapidly in all calves given the Fe or Mo supplements or both. Levels indicative of severe Cu deficiency were attained within 16 weeks. There were no significant differences in values in animals given Fe, Mo or Fe plus Mo. 3. Clinical signs of Cu deficiency developed after 20 weeks in the calves given the Mo supplement. Growth rates were reduced, skeletal lesions developed and hair texture and colour were affected. No such effects were observed in the calves given only the Fe supplement. 4. Plasma and liver Fe concentrations increased in calves given the Fe supplement but were not greatly affected by Mo, even when the calves were severely Cu-deficient. 5. The significance of the effects of Fe and Mo on Cu metabolism are discussed with special regard to the influence of soil ingestion on Cu availability and to the frequent lack of correlation between the Cu status of animals and their clinical condition.

Animals↗
PubMed1982

An EXAFS study of the zinc sites in sheep liver metallothionein.

Measurement and interpretation of the EXAFS associated with the K-absorption edge of zinc atoms in sheep liver metallothionein indicate that the primary coordination shell of each of these metal atoms comprises four sulphur atoms, with the Zn-S distance being 2.29 +/- 0.02 A.

Animals↗
PubMed1982

Copper metabolism in rats given di- or trithiomolybdates.

As one of a series of studies on the influence of S substitution of MoO4(2-) on the action of Mo as an antagonist of Cu, the effects of MoO2S2(2-) and MoOS3(2-) on the metabolism of Cu by rats have been investigated. Administration of either oxythiomolybdate increased both plasma Cu concentration and the retention of Cu by the albumin fraction of plasma. In contrast to the effects of MoS4(2-), described previously, neither oxythiomolybdate inhibited 64Cu absorption from the digestive tract or induced biochemical or clinical signs of Cu deficiency. Evidence is discussed suggesting that the potency of the thio- and oxythiomolybdates as inhibitors of Cu utilization is directly proportional to the degree of thio substitution within the series series MoO4- chi S chi 2-.

Animals↗
PubMed1982

Effects of tetrathiotungstate and dithiotungstate on copper metabolism in rats.

The effects of dietary supplementation with ammonium tetrathiotungstate and dithiotungstate on copper metabolism in young rats have been investigated. The addition of WS4(2-) (4-32 mg W/kg diet) decreased growth rates and induced clinical and biochemical signs of Cu deficiency. These were overcome by increasing the dietary content of Cu. The intestinal absorption of 64Cu was impaired and the tissue distribution of absorbed Cu modified by the administration of WS4(2-). No clinical or biochemical defects indicative of Cu deficiency developed in rats receiving WO2S2(2-) in their diet at concentrations up to 32 mg W/kg. In contrast, this oxythioanion enhanced the content of Cu in plasma liver and kidney, especially when dietary Cu was increased. Most of the additional Cu retained by plasma and kidney was associated with albumin and metallothionein, respectively. The effects of these W sources are compared with those caused by their thio- and oxythiomolybdate analogs and are discussed in relation to the mechanisms whereby Mo induces Cy deficiency in ruminants.

Animals↗
PubMed1981

Absorption, transport and tissue storage of essential trace elements.

Intestinal absorption of many essential trace elements probably occurs by saturable and carrier-mediated processes. The nature and efficiency of these are influenced by a range of physiological, nutritional and genetic variables. Special emphasis is given to the influence of exogenous and endogenous ligands of small molecular mass in the intestinal lumen on absorptive efficiency. The effect of enterocyte proteins such as metallothionein which, by sequestering metals, influence their fate during absorption is also considered. Changes in the metabolic activity of the intestinal mucosa induced by copper or zinc deficiencies influence the fate of other nutrients, either by inhibiting intracellular transport or by preventing the degradation of potential antagonists of absorption. Conflicting evidence of roles for plasma albumin, transferrin and caeruloplasmin in the transport of zinc and copper is considered. The extent, location and form in which trace elements are stored in tissues differs between elements and between species. Retention and utilization are also influenced by pregnancy, lactation, stage of foetal development and by genetic variables. Better definition of the effects of these variables would improve the validity of estimates of the trace element requirements of man and other animals.

Animals↗