Mechanisms Underlying The Selective Removal Of Copper From Copperbinding Mt By

Formation of Three Different Complexes Between Copper and TTM In Vitro Depending on the Relative Molar Ratio of TTM to Copper Tetrathiomolybdate forms different complexes with Cu (Cu2+) in vitro depending on the relative ratio of TTM to Cu, which can be monitored spectroscopically by the change at the characteristic absorbances of 240, 315, and 465 nm. When Cu is present in the form bound to MT (i.e., Cu-MT or Cu,Zn-MT), three different complexes are formed on a gel filtration HPLC column...

Reinhard Wimmer Charles T Dameron and Marc Solioz

In the past, copper transport in bacteria has been considered only in terms of resistance mechanisms to permit survival of the cells in adverse copper-rich environments. Indeed, most of the systems characterized early on are plasmid encoded, as is typical for defense mechanisms of prokaryotes. Recently, similar copper resistance systems were also identified in chromosomal locations, giving rise to the concept that bacteria may need systems for copper homeostasis not only in extreme environments...

Erik Vijgenboom and Bart Keijser

Redox active metal ions such as copper are potentially dangerous to a cell because of their habit of engaging in all kinds of reaction generating, among others, reactive oxygen species. However, these metal ions play a crucial role as a cofactor in a variety of enzymes and electron-transport proteins. Recently, it has become evident that copper ions play an intriguing role in the morphogenesis of Streptomyces. This Gram-positive bacterium undergoes a complicated cycle of morphological...

Simonetta Ferruzza Yula Sambuy Andrea Onetti Muda Fabio Nobili and Maria Laura Scarino

COPPER AND INTESTINAL TOXICITY Copper in humans plays different roles It is an essential nutrient, but, depending on the dose, it can act as a toxic substance. However, it remains controversial where to set the limits between essential and toxic levels of intake. Sensitive and accurate indicators of copper toxicity at the level of the gastrointestinal tract are still missing, and those available (e.g., nausea, vomiting, abdominal pain) do not discriminate from other toxicants and respond at...

References

Sternlieb, I. (1980) Copper and the liver. Gastroenterology 78, 1615-1628. 2. Schilsky, M. L. and Sternlieb, I. (1993) Animal models of copper toxicosis. Anim. Mod. Liver Res. 37, 357-377. 3. Pandit, A. N. and Bhave, S. A. (1983) Copper and Indian childhood cirrhosis. Indian Pediatr. 20, 893-899. 4. Bull, P. C., Thomas, G. R., Rommens, J. M., Forbes, J. R., and Cox, D. W. (1993) The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene. Nature Genet. 5,...

David R Brown

The names bovine spongiform encephalopathy (BSE), Creutzfeldt-Jakob disease (CJD), and scrapie are now household names despite the fact that the human disease (CJD) remains a disease of very low incidence, accounting for 1 in 106 deaths per annum worldwide. BSE and CJD are examples of prion diseases, fatal neurodegenerative conditions (1). Before the BSE epidemic, prion diseases were infamous because the cause could not be linked to a known pathogen such as a virus or bacterium but to a single...

Results

Cloning and Tissue Expression of Bis A partial clone of Bis, the product of the Bag-3 gene, a member of the Bcl-2 associated athanogene family of Bcl-2-binding proteins (36), was originally isolated from a cDNA library obtained from HeLa cells grown for 10 h in the presence of 250 M ZnCl2 (37). Comparison by Blast analysis with the Bag-3 gene sequence present in GenBank confirmed that the nucleotide sequence of this clone corresponded to Bis sequences in the region between nucleotides 915...

Effect Of Copper On Tightjunctions Permeability

The effect of copper on epithelial permeability was investigated by our group using the Caco-2 cell line (49). In ref. 49, CuSO4 was added either to the AP or to the BL compartment at pH 7.4 in complete medium for 24 h. Under these conditions, copper was chelated by amino acids and proteins (e.g., albumin) present in the complete medium and an increase in monolayer permeability was only observed after treatment with 100 pM CuSO4 from the BL side, which resulted in cellular damage, as shown by a...

Iron Metabolism in the Budding Yeast Saccharomyces cerevisiae

The experiments that confirmed the role of multicopper oxidases in iron metabolism in vertebrate systems came from studies on iron transport in yeast. Yeast, particularly the budding yeast Saccharo-myces cerevisiae is perhaps the simplest of the eucaryotes, as they grow as single cells and can be both haploid and diploid The haploid status of yeast permits the selection of yeast mutants. Once a phenotype has been selected, genes responsible for modifying a specific phenotype can be identified...

Info

Microphotograph of differentiated Caco-2 cells on a polycarbonate filter. Caco-2 cells grown on a filter and differentiated for 19 d were embedded in metacrylate resin (JB4 Polysciences Inc., Warrington, PA) and cut into 3- M-thick sections, stained with hematoxylin-eosin and observed by light microscopy. The cells appear well polarized with basal nuclei and a regular brush border on the AP surface. Bar 8 J,m. 2-3 wk and leads to the formation of a monolayer of cells coupled by...

Heterologous And Homologous Expression Of Smmo And The Role Of Copper Ions

The genes mmoB and mmoC, encoding the coupling protein, protein B, and the reductase component (protein C), have been expressed in Escherichia coli using a T7 polymerase expression system to yield active protein B and protein C (18). This has allowed site-directed mutagenesis experiments on protein B. Protein B in Methylococcus is subject to N-terminal cleavage between residues Met-12 and Gly-13, which results in the inactivation of this effector regulatory polypeptide. Substitution of Gly-13...

Shinya Yoshikawa

Cytochrome oxidase is the terminal oxidase of most of aerobic organisms and reduces molecular oxygen (O2) to water (1). The electrons and protons required for the formation of water molecules are transferred from both sides of the mitochondrial inner membranes in eukaryotic cells and of the cell membrane in prokaryotic cells (1). The migration of positive and negative charges from the different sides of the membrane produces electric potential across the membrane. In addition to the O2...

Identification and Characterization of FET3

Using a selection system that was enriched for mutants unable to grow on low-iron media, Askwith et al. reported the identification of a mutant, fet3, that was unable to grow on low-iron media (14). This mutant had a normal surface reductase activity but was unable to accumulate 59Fe. A gene that could complement both the low-iron growth defect and the inability to accumulate radioactive iron was identified by complementation of the mutant strain with a genomic library. Genetic studies...

Copper In Diseases And Genetic Diseases Of Copper Metabolism

Inflammation, Infection, and Cancer Copper metabolism is altered in inflammation, infection, and cancer. As already mentioned, plasma ceruloplasmin is an acute-phase reactant, and synthesis and secretion of the protein by hepatocytes is stimulated by inflammatory cytokines (particularly interleukin-1 IL-1 and IL-6) (1,5). The increase in ceruloplasmin may protect cells from radicals released to combat the influx of foreign organisms or antigens, because it is a general radical scavenger,...

Menkes Disease

Menkes disease MD is a multisystemic lethal disorder of copper metabolism, inherited as an X-linked recessive trait. Progressive neurodegeneration and connective tissue manifestations together with peculiar kinky hair are the main manifestations 2,13 . Although many patients present a severe clinical course, variable forms can be distinguished, and the occipital horn syndrome OHS is the mildest recognized form. Clinical and physiopathological features of MD are attributable to deficiency of one...

Edward J Massaro

The National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC Although copper is an essential trace element necessary for the survival of organisms ranging from bacteria to mammals, it is also highly toxic and must be absorbed by the body in precisely orchestrated biological processes. In Handbook of Copper Pharmacology and Toxicology, Edward J. Massaro and a panel of leading biomedical researchers and clinical practitioners review, in-depth, the status of our...