Metallothionein induction by cadmium and zinc in rat secretory organs

Metallothionein (MT) levels were determined in four secretory organs of the rat following administration of zinc (Zn) and cadmium (Cd). The concentrations of MT in the lacrimal, parotid and adrenal glands of untreated rats were in the range of 2.2-4.9 micrograms/g wet weight tissue while in the pancreas it was shown to be 15.2 micrograms/g. Injection of zinc at total doses of 16, 32 and 80 mg/kg resulted in a 1.8-, 3.2- and 5.9-fold increase in lacrimal MT content, respectively, while a 10.2- and 13.1-fold elevation was observed following treatment with 4 and 8 mg/kg of Cd, respectively. Similar findings were found in the adrenal gland. The parotid MT was elevated 5.9 and 17 times following Zn treatment at doses of 16 and 80 mg/kg respectively, whereas 4 mg/kg of Cd increased MT 14.4 times in this gland. Pancreatic MT was elevated by 39- and 40-fold after injection of Zn at doses of 16 and 32 mg/kg respectively, whereas 4 and 8 mg/kg of Cd caused a 9.8- and 17.9-fold induction, respectively. These results may indicate that secretory organs participate in metabolism of heavy metals in the mammalian body.     

The enhanced induction of metallothionein by zinc,its half-life in the marine fishPleuronectes platessa,and the influence of stress factors on metallothionein levels

Summary Intraperitoneal injection of zinc raised levels of a hepatic metallothionein-like species. Assuming that this species was metallothionein (MT) then levels were raised from approximately 20 g/g to 300 g/g in 7 days, and levels thereafter remained high for the next 4 weeks. The half-lives of the protein in liver and kidney from starved fish, measured using in vivo incorporation of³⁵S cysteine at 11°C, were approximately 27 days and 32 days respectively. The following agents failed to stimulate synthesis of MT in plaice: stress (due to catching), endotoxin, dexamethasone, cortisol and turpentine.     

Uptake and toxic effects of heavy metal ions: Interactions among cadmium,copper and zinc in cultured cells

Summary Absorption of metal ions by KB, HeLa and L-59 cells has been analyzed by atomic absorption spectrophotometry in the course of culture. Ions of the elements of the fourth period in the periodic chart such as Fe(II), Cu(II), Zn(II), Mn(II) and Ni(II) were not taken up, but those of the higher periods, such as Cd(II), Pb(II), Hg(II) and Ag(I) were were taken up easily. The uptake behavior by the cultured cells was in accordance with the characteristic features of metals, that metals in the fourth period are essential elements, and most of the elements of the fifth and the sixth periods are non-essential or toxic elements.The initial rate of Cd(II) uptake and the Cd(II) concentration has a sigmoidal relationship. Cd(II) was absorbed homotropically through cell membranes. The uptake of Cd(II) was specifically inhibited by Cu(II), but was affected little by Zn(II). The toxicity of Cd(II) to KB cells was greatly enhanced in the presence of Cu(II). On the contrary, the toxicity of Cd(II) was reduced by the addition of Zn(II) at several concentrations of Cd(II). The toxicity of Cd(II) did not depend on the amount of Cd(II) absorbed in the cells, but was determined by cofactors such as Cu(II). The interaction between Cd(II) and Cu(II) may be important for Itai-itai disease.     

Substance P-like immunoreactive fibers in the frog taste organs

Summary In the frog tongue, substance P(SP)-like immunoreactive fibers were consistently present in each fungiform papilla, which contained the gustatory apparatus. Numerous SP-like immunoreactive fibers were usually distributed in the periphery of the gustatory disc and formed a varicose meshwork among the ciliated cells encircling the gustatory disc. SP-like immunoreactive fibers were rarely evident inside the gustatory disc. The role of SP-containing fibers in the frog taste organ was discussed.     

Restraint stress induced changes in rat liver and serum metallothionein and in Zn metabolism

Summary 24 h of a psychogenic stress (restraint) caused a strong increase of liver metallothionein (MT) levels. 3 h of stress were sufficient to induce an increase in liver MT, measured 21 h later, but the increase was much lower than in continuously restrained rats. Stress induction of liver MT was not due to food deprivation, since rats deprived for 24 h showed lower MT levels than stressed ones. Zn on MT presented the same qualitative but not quantitative pattern of response as MT protein. Liver cytosolic Zn was increased by restraint in spite of their being no decrease in serum Zn. Any treatment altered serum MT. Liver and serum MT were not correlated. The present results demonstrate that basically psychogenic stresses increased liver but not serum MT levels. No positive evidence for a relationship between corticosterone secretion and MT induction was found.     

Deciduoma induction in the rat by X-irradiation

Riassunto Una dose di 500–1000 r di raggi X, data localmente ad un lato dell'addome di ratte al quinto giorno di pseudogravidanza, ha stimolato la formazione di deciduomi nel corno uterino irradiato di metà degli animali. L'esame istologico ha rivelato che i deciduomi presentavano tipiche caratteristiche isto-morfologiche, ma erano 1/2-1/4 delle dimensioni medie dei deciduomi indotti traumaticamente. La formazione di un deciduoma anche in un corno dalla parte non irradiata potrebbe indicare che, sia un fattore locale che uno generale contribuiscono al meccanismo induttore.     

Isolation,characterization, and determination of human liver (copper/zinc) metallothionein

Summary A copper-containing protein was purified from the liver of a patient with primary biliary cirrhosis by a combination of gel filtration and anion exchange chromatography. This copper-protein had UV absorption and emission spectra, an amino acid composition, and a molecular mass which were characteristic for metallothionein (MT).From 8 livers (3 control, 1 fetal and 4 primary biliary cirrhosis) MT was extracted with non-reducing buffer and centrifuged, and the pellets were re-extracted with a 1% 2-mercaptoethanol-containing buffer. The non-reducing buffer extracted a predominantly copper-containing MT from the livers of patients with primary biliary cirrhosis and a predominantly zinc-containing MT from control lives and the fetal liver. Only from the fetal liver was a copper/zinc containing MT solubilized during the re-extraction with 2-mercaptoethanol-containing buffer. These results indicate that human MT is a unique metalloprotein with age and disease-dependent characteristics.     

The molecular mechanism of zinc and cadmium stress response in plants

When plants are subjected to high metal exposure, different plant species take different strategies in response to metal-induced stress. Largely, plants can be distinguished in four groups: metal-sensitive species, metal-resistant excluder species, metal-tolerant non-hyperaccumulator species, and metal-hypertolerant hyperaccumulator species, each having different molecular mechanisms to accomplish their resistance/tolerance to metal stress or reduce the negative consequences of metal toxicity. Plant responses to heavy metals are molecularly regulated in a process called metal homeostasis, which also includes regulation of the metal-induced reactive oxygen species (ROS) signaling pathway. ROS generation and signaling plays an important duel role in heavy metal detoxification and tolerance. In this review, we will compare the different molecular mechanisms of nutritional (Zn) and non-nutritional (Cd) metal homeostasis between metal-sensitive and metal-adapted species. We will also include the role of metal-induced ROS signal transduction in this comparison, with the aim to provide a comprehensive overview on how plants cope with Zn/Cd stress at the molecular level.     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Effect of latent iron deficiency on the levels of iron,calcium, zinc,copper, manganese,cadmium and lead in liver,kidney and spleen of growing rats

Summary Feeding a marginally low iron content diet (18–20 mg iron/kg diet) to weaned (21-day-old) rats for 8 weeks produced a significant decrease in liver non-heme iron (66%, p<0.001) but no change in blood hemoglobin. Total iron contents of liver (56%, p<0.01), spleen (20%, p<0.05), and kidney (19%, p<0.05) were also found to decrease along with increased zinc, copper, calcium, manganese lead and cadmium in various organs. The magnitude of alteration of a metal was different in different organs. However, liver was found to be the most affected organ. Two weeks of rehabilitation with iron-sufficient diet (390 mg iron/kg diet) normalized these altered levels.     

Effects of dosage and cadmium pretreatment on the binding of cadmium in rat bile.

The effects of dosage and of cadmium pretreatment on the binding of cadmium in rat bile were studied. With increasing dose a higher cumulative biliary excretion of Cd was observed and a higher percentage of the Cd was excreted in a low-molecular-weight form. On the other hand, after cadmium pretreatment, a decrease in the cumulative biliary excretion of cadmium was observed but a greater percentage of that excreted into the bile was bound to high molecular weight compounds.     

The role of serpins in the surveillance of the secretory pathway

Serpins (serine protease inhibitors) constitute a class of proteins with an unusually wide spectrum of different functions at extracellular sites and within the nucleocytoplasmic compartment that extends from protease inhibition to hormone transport and regulation of chromatin organization. Recent investigations reveal a growing number of serpins acting in secretory pathway organelles, indicating that they are not simply cargo destined for export, but fulfill distinct roles within the classical organelle-coupled trafficking system. These findings imply that some serpins are part of a quality control system that monitors the export and possibly import routes of eukaryotic cells. The molecular targets of these serpins are often unknown, opening new avenues for future research.     

Immunocytochemical demonstration of calmodulin in cells secreting by exocytosis

Summary Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreatic-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.     

Uptake of labelled histones by isolated perfused rat liver and by various organs of the intact mouse

Résumé Des histones marquées au H³ ont été administrées à des souris par voie intrapéritonéale. La pénétration d'histones dans le foie isolé en perfusion est rapide. Les noyaux contiennent une quantité plus ou moins proportionnelle à leur volume dans la cellule et la majorité de l'activité a pu être isolée comme histones liées à la chromatine.     

Mechanism of induction of tyrosine in rat liver by phenothiazine derivatives and related chemical compounds]

Increase of hepatic tyrosine-alpha-ketoglutarate transaminase is observed in Rats (Wistar strain) after intraperitoneal administration of tricyclic compounds (phenothiazin and related structure derivatives). This is an induction process: actinomycine D inhibits this effect. This action is not mediated by glucocorticoids: induction persists in adrenalectomized Rats. The mechanism of action is different too: additive effects are found after simultaneous injection of glucocorticoid and tricyclic drug.     

Morphogenesis of human colon cancer cells with fetal rat mesenchymes in organ culture

Summary The morphogenesis and cytodifferentiation of human colon cancer cells (LS174T and HT29) were examined by combining cancer cells with fetal rat digestive-tract mesenchyme in organ culture. LS174T cells migrated into the mesenchyme to form glandular structures composed of single columnar cells with their nuclei oriented basally, while HT29 cells formed cell masses with little lumen formation. Immunohistochemical studies with antibodies against carcinoembryonic antigen and secretory components showed that the composition of cell surface glycoproteins was not necessarily reversed to the normal type, even when neoplastic cells exhibited normal glandular structures.This work was supported by grants-in-aid for Cancer Research from the Ministry of Education, Science, and Culture, Japan, and by the Veterans Administration Medical Research Service, USA. Y.S. Kim is the recipient of a Medical Investigator Award of the Veterans Administration.