Copper intracellular distribution

Soldo D, Hari R, Sigg L, Behra R (2005) Tolerance of Oocystis nephrocytioides to copper intracellular distribution and extracellular complexation of copper. Aquat Toxicol 71 307... 

Whanger. P.D. and P.H, Weswig Effect of Supplementary Zinc on the Intracellular Distribution of Hepatic Copper in Rats, J. Nutrition, 101, 1093 (1971). 

Regulation of Gene Expression and Intracellular Copper Handling. Copper-dependent proteins act as transcription factors for specific genes, such as those regulating SOD and catalase. Metallothionein synthesis is controlled by copper-responsive transcription factors, and this protein is important in regulating the intracellular distribution of copper, Additional specialized proteins act as copper chaperones to deUver copper to intracellular sites and prevent oxidative damage by free copper ions. ... 

The intracellular distribution of copper has been studied. A distinct pattern of distribution was foimd among the four subcellular fractions that can be separated by differential centrifugation. In rat liver, 64.3% of the total copper is found in the soluble fraction, 8.2% and 5.0% in the mitochondrial and microsomal fractions, respectively, and 20.3% in the fraction containing nuclei and cell residue. These results obtained by Thiers and Vallee (T2) were confirmed by Hermann and Kun (HIO). In the livers obtained at autopsy of two adult men. Porter has found a similar subcellular distribution of copper (Pll, P15). 

Pll. Porter, H., The intracellular distribution and chromatographic separation of copper proteins in Wilson s disease. Trans. Am. Neurol. Assoc. 88, 159-164 (1963). 

In mammals, as in yeast, several different metallothionein isoforms are known, each with a particular tissue distribution (Vasak and Hasler, 2000). Their synthesis is regulated at the level of transcription not only by copper (as well as the other divalent metal ions cadmium, mercury and zinc) but also by hormones, notably steroid hormones, that affect cellular differentiation. Intracellular copper accumulates in metallothionein in copper overload diseases, such as Wilson s disease, forming two distinct molecular forms one with 12 Cu(I) equivalents bound, in which all 20 thiolate ligands of the protein participate in metal binding the other with eight Cu(I)/ metallothionein a molecules, with between 12-14 cysteines involved in Cu(I) coordination (Pountney et ah, 1994). Although the role of specific metallothionein isoforms in zinc homeostasis and apoptosis is established, its primary function in copper metabolism remains enigmatic (Vasak and Hasler, 2000). 

We have previously demonstrated that the extent of intracellular re-distribution and mobilization of iron, copper and proteins into the coronary flow depends on ischemic duration, and could serve as predictive criteria for the degree of heart injury [10,11]. The observed increase in iron and copper levels in the CFF ( free and bound states) resulted in the increase in free radicals production, which in turn could explain the post-ischemic heart damage. 

Metallochaperones (like ATOX 1) transfer copper to the site of synthesis of copper containing proteins (Rae et al., 1999 Huffman and O Halloran, 2002). The cytoplasmic copper chaperone ATOXl is required for copper delivery to ATP7B by direct protein-protein interaction (Hamza et al., 1999 Walker et al., 2002). ATP7B is abundantly expressed in hepatocytes and is localized in these cells to the late secretory pathway, predominantly the tran -Golgi network. With increasing intracellular copper concentrations, this ATPase traffics to a cytoplasmic vesicular compartment that distributes near the canaUcular membrane in polarized hepatocytes and... 

Intracellular thiol concentration is concomitantly depleted and the sequestering by formation of Cu(I)SR confirmed. This is nonspecific and copper seems evenly distributed throughout the cell [61]. This copper-catalyzed oxidation accounts for the increased oxygen consumption. 

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