Stress proteins copper

Sanders, B.M., L.S. Martin, S.R. Howe, W.G. Nelson, E.S. Hegre, and D.K. Phelps. 1994. Tissue-specific differences in accumulation of stress proteins in Mytilus edulis exposed to a range of copper concentrations. Toxicol. Appl. Pharmacol. 125 206-213. 

Sanders, B.M., J. Nguyen, L.S. Martin, S.R. Howe and S. Coventry. Induction and subcellular localization of two major stress proteins in response to copper in the fathead minnow Pimephales promelas. Comp. Biochem. Physiol. 112C 335-343, 1995. 

The proximal mechanism for induction of stress protein synthesis leading to the activation of HSF and gene activation is not completely understood, but evidence for several possibilities exists. Activation of HSF by prooxidants does not result in the accumulation of specific stress proteins (Bruce et al. 1993). These results suggest that induction of stress proteins by specific metals, whose toxicity is mediated via oxidative damage to membranes or DNA, may be fundamentally different from that of the heat-induced activation of the stress response (Keyse and Tyrrell 1987 Bruce et al. 1993). Thus, metals such as cadmium, mercury, nickel, arsenite, copper, lead, and iron, which induce oxygen free radicals or promote formation of lipid peroxides (Stacey and Klaassen 1981 Halliwell and Gutteridge 1984 Christie and Costa 1984 Kasprzak 1991 Donati et al. 1991), may... 

The intracellular localization of stress proteins is problematic for the evaluation of the response in humans. Because the cells for the assay of stress proteins are not readily available through noninvasive procedures, the application of this response to human monitoring is limited. Recently, however, enhanced synthesis of stress proteins was demonstrated in primary cultures of human lymphocytes exposed to several metals (Yamada and Koizumi 1993). The specificity of the response was dependent on the metal to which the cultures were exposed. For example, cadmium and zinc induced both hsp70 and MT, while cobalt and triphenyltin induced only hsp70. Conversely, copper, mercury, nickel, and silver all induced synthesis of MT, but not of hsp70. Enhanced synthesis of stress proteins has also been demonstrated in vivo in lymphocytes and spleen cells excised from mice exposed to hyperthermia (Rodenhiser et al. 1985). 

Sanders BM, Martin LS, Nelson WG, Phelps DK, Welch W (1991) Relationships between accumulation of a 60 kDa stress protein and scope-for-growth in Mytilus edulis exposed to a range of copper concentrations. Marine Environ Res 31 81-97... 

In concluding this section, we stress again the novel dependence of the extracellular connective structures on chemistry, especially that of copper and iron using oxygen, and zinc proteins for hydrolysis, which did not and could not have taken place before more than one billion years ago. They arose mainly after the development of unicellular eukaryotes, and were dependent on additional environmental change. Even several external uses of calcium depend upon new oxidation of the side chains of proteins. 

Suresh, K. and A. Mohandas. 1993. Haemolymph protein levels in copper-stressed bivalves. Sci. Total Environ., Suppl. 1993, Part 1 631-639. 

There is considerable evidence that defective homeostasis of redox-active metals, i.e. iron and copper, together with oxidative stress, contributes to the neuropathology of AD. The characteristic histology of AD is the deposition of both Ap, as neurotic plaques (Figure 18.12a), and of the protein tau, as neurofibrillary tangles NFT (Figure 18.12b), predominantly in the cerebral cortex and hippocampus. 

Recent publications signal the continued interest in the function of this protein. It has been called a stress enzyme, involved in influenza virus infection (Tomas and Toparceanu, 1986). An explanation for Wilson s disease in terms of a genetic defect resulting in failure to convert from a neonatal (i.e., low) level of ceruloplasmin and copper to a normal adult level has been reported (Srai et al., 1986). Tissue specificity for the binding of ceruloplasmin to membranes was demonstrated in a study investigating the possible role of ceruloplasmin-specific receptors in the transfer of copper from ceruloplasmin to other copper-containing proteins (Orena et al, 1986). Ceruloplasmin has been shown to be effective in transferring copper to Cu,Zn-SOD in culture (Dameron and Harris, 1987), as has copper albumin. In view of the variable content of copper in this protein, it is not clear which copper is transferred. 

Table I lists isomorphous replacements for various metalloproteins. Consider zinc enzymes, most of which contain the metal ion firmly bound. The diamagnetic, colorless zinc atom contributes very little to those physical properties that can be used to study the enzymes. Thus it has become conventional to replace this metal by a different metal that has the required physical properties (see below) and as far as is possible maintains the same activity. Although this aim may be achieved to a high degree of approximation [e.g., replacement of zinc by cobalt(II)], no such replacement is ever exact. This stresses the extreme degree of biological specificity. The action of an enzyme depends precisely on the exact metal it uses, stressing again the peculiarity of biological action associated with the idiosyncratic nature of active sites. (The entatic state of the metal ion is an essential part of this peculiarity.) Despite this specificity, the replacement method has provided a wealth of information about proteins that could not have been obtained by other methods. Clearly, there will often be a compromise in the choice of replacement. Even isomorphous replacement that should retain structure will not necessarily retain activity at all. However, it has become clear that substitutions can be made for structural studies where the substituted protein is inactive (e.g., in the copper proteins and the iron-sulfur proteins). It is also possible to substitute into metal coenzymes. Many studies have been reported of the...

If our postulates are correct the most interesting feature of P-450 is the manner in which the protein has adjusted the coordination geometry of the iron and then provided near-neighbour reactive groups to take advantage of the activation generated by the curious coordination. Vallee and Williams (68) have observed this situation in zinc, copper and iron enzymes and referred to it as an entatic state of the protein. It is also apparent that some such adjustment of the coordination of cobalt occurs in the vitamin B12 dependent enzymes. As a final example we have looked at the absorption spectra of chlorophyll for its spectrum is in many respects very like that of a metal-porphyrin. This last note is intended to stress the features of chlorophyll chemistry which parallel those of P-450. 

Copper is essential for some of the enzymes that have a role in brain metabolism. Sophisticated mechanisms balance copper import and export to ensure proper nutrient levels (homeostasis) while minimizing toxic effects. Several neurodegenerative diseases including AD are characterized by modified copper homeostasis. This change seems to contribute either directly or indirectly to increased oxidative stress, an important factor in neuronal toxicity. The association of misfolded proteins and modified copper homeostasis appears to be important in the pathological progression of AD [Donnelly et al., 2007],... 

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