Mercury-binding protein

Barghigiani, C., D. Pellegrini, and E. Carpene. 1989. Mercury binding proteins in liver and muscle of flat fish from the northern Tyrrhenian Sea. Comp. Biochem. Physiol. 94C 309-312. 

While studying the binding of mercury by chromatin of rats injected with mercuric chloride, the nonhistone chromatin proteins in rat and kidney cell nuclei were shown to be mainly responsible for the mercury deposition [43]. The mercury-binding nonhistone proteins were found to be heterogeneous by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. 

Elemental mercury is oxidized in vivo to inorganic mercury, a bio transformation that is probably catalyzed by catalase. It is selectively accumulated in the kidney and also by lysosomes. Inorganic mercury (Hg2+) will induce the synthesis of metallothionein. Mercury binds to cellular components such as enzymes in various organelles, especially to proteins containing sulfydryl groups. Thus, in the liver, cysteine and GSH will react with mercury to produce soluble products, which can be secreted into the bile or blood. 

We have seen (Section 56.1.13.2.2) that cadmium can induce the synthesis of a Cd-binding protein in fact, the administration of copper, zinc, cadmium or mercury to animals induces the synthesis of these proteins called metallothioneins, which play an important role in the metabolism of these elements. 

Inorganic mercury salts, however, are primarily nephrotoxicants, with the site of action being the proximal tubular cells. Mercury binds to SH groups of membrane proteins, affecting the integrity of the membrane and resulting in aliguria, anuria, and uremia. 

Mercury. Mercury exerts its principle nephrotoxic effect on the membrane of the proximal tubule cell. In low concentrations, mercury binds to the sulfhydryl groups of membrane proteins and acts as a diuretic by inhibiting sodium reabsorption. Organomer-curial diuretics were introduced into clinical practice in the 1920s and were used... 

MacGregor, J. T. and Clarkson, T. W. (1974). Distribution, tissue binding and toxicity of mercurials. In "Protein-Metal Interactions", (M. Friedman, ed.), Plenum Press, New York, pp. 463-503. 

It is well known that a large number of chemical substances, including toxic metals and metalloids such as arsenic, cadmium, lead, and mercury, cause cell injury in the kidney. With metal-induced neurotoxicity, factors such as metal-binding proteins, inclusion bodies, and cell-specific receptor-like proteins seem to influence renal injury in animals and humans. It is of interest to note that certain renal cell populations become the targets for metal toxicity, while others do not. In fact, the target cell populations handle the organic and common inorganic nephrotoxicants differently. ... 

One of the first metalloregulatory proteins to be characterized extensively is the prokaryotic MerR transcription factor (1, 6, 7), which acts either as a repressor (apo-protein) or an activator (holo-protein) of the mer operon encoding mercury resistance proteins (Fig. Ic). The —35 and —10 sequence elements of the mer promoter, binding sites for the RNA polymerase initiation complex, are separated by an unusually long distance that results in poor constitutive transcription. Apo-MerR binds to the DNA between these sequences and bends the DNA, which results in a slight increase in repression on the suboptimal promoter. It also recruits the RNA polymerase to the transcription start site where it waits in a stalled complex. Upon binding of... 

Roels et al. [63] and Buchet et al. [118] observed a slightly higher prevalence of elevated urinary excretion of albumin, transferrin, retinol binding protein and the tubular enzyme [l-galactosidase in chloralkali workers with a urinary excretion of mercury exceeding 50 pg/ g creatinine. 

Attempts to define threshold levels for effects have produced mixed results. A no-efifect level of 72 g Hg/g creatinine was determined for urinary excretion of albumin, 2-microglobulin, or retinol binding protein (Bernard et al. 1987). However, other studies have shown increases in urinary albumin at urinary mercury levels >50 g Hg/g creatinine (Buchet et al. 1980) and increases in urinary /V-acetyl-... 

The divalent cation exists in both a nondiffusible form (tissues) and a diffusible form (blood) (Halbach and Clarkson 1978 Magos 1967) (see Section 2.3.2). The mechanism for the distribution of mercury and its compounds probably depends on the extent of uptake of the diffusible forms into different tissues or on the mercury-binding to protein-binding sites (sulfhydryl groups) in red cells and plasma proteins (Clarkson 1972b). 

Webb M, Holt D. 1982. Endogenous metal binding proteins in relation to the differences in absorption and distribution of mercury in newborn and adult rats. Arch Toxicol 49 237-245... 

Cadmium shares chemical properties with zinc and mercury, but in contrast to mercury, it is incapable of environmental methylation, due to the instability of the monoalkyl derivate. Similarities and differences also exist in the metabolism of Zn, Cd, and Hg. Metallothioneins and other Cd-binding proteins hold or transport Cd, Zn, and Hg within the body. Metallothioneins are metal-binding proteins of relatively low molecular mass with a high content of cysteine residues that have a particular affinity for cadmium, as well as for zinc and copper, and can affect its toxicity. 

Marafante, M.. Binding of mercury and zinc to cadmium-binding protein in the liver and kidney of goldfish (Carassius auratus L.). Experientia 32 149-150, 1976. 

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