Metallothionein differentiation

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). 

Metallothioneins (MT), low molar mass proteins, have been studied electrochemi-cally alone and in the presence of Cd(II) and Zn(II) ions [110-115]. The electrochemical behavior of zinc MTs from rabbit liver, with respect to solution pH, as well as the influence of the addition of zinc [116] and also zinc MT from rat liver, was investigated [117] using electroanalytical techniques. Studies of complexing properties of the alpha-MT with Zn(II) were carried out using differential pulse po-larography [118]. 

Palmiter, R. D., Chen, H. Y. and Brin-ster, R. L. (1982) Differential regulation of metallothionein-thymidine kinase fusion genes in nansgenic mice and their offspring. Cell 29, 701-710. 

Trayhum P, Duncan JS, Wood AM, Beattie JH (2000) Regulation of metallothionein gene expression and secretion in rat adipocytes differentiated from preadipocytes in primary culture. Horm Metab Res 32 542-547... 

Ramseier U, Chang JY. Modification of cysteine residues with N-methyl iodoacetamide. Analyt. Biochem. 1994 221 231-233. Bernhard WR. Differential modification of metallothionein with iodoacetamide. Methods Enzymol. 1991 205 426-433. 

Tio L, Villarreal L, Atrian S, and Capdevila M (2004) Functional differentiation in the mammalian metallothionein gene family, metal binding features of mouse MT4 and comparison with its paralog MTl. Journal of... 

In plants, two kinds of metal-binding peptides or proteins are synthesized. Plant metallothioneins are inducible cysteine-rich entities very like those found in animals. Differential expression (induction) of metallothionein genes can be due to both variation of external heavy metal concentrations and the influence of various environmental factors. The principle role of plant metallothioneins seems to be in homeostasis rather than in metal detoxification. Plants are also known to have so-called phytochelatins, which are non-protein thiols specifically induced upon exposure to heavy metals. A close positive relationship between the concentrations of cadmium and phytochelatins in the plant shoot material has been observed and linked to the degree of growth inhibition (Keltjens and Van Beu-sichem, 1998). These observations make the use of phytochelatins promising for the assessment of heavy metal effect on plants. 

Interaction with metallothionein is the basis for metabolic interactions between these metals. Metallothionein III is found in the human brain and differs from I and II by having six glutamic acid residues near the terminal part of the protein. Metallothionein III is thought to be a growth inhibitory factor, and its expression is not controlled by metals however, it does bind zinc. Another proposed role for metallothionein III is participation in the utilization of zinc as a neuromodulator, since metallothionein III is present in the neurons that store zinc in their terminal vesicles. Metallothionein IV occurs during differentiation of stratified squamous epithelium, but it is known to have a role in the absorption or toxicity of cadmium. 

Kling, P.E. and P. Olsson. Involvement of differential metallothionein expression in free radical sensitivity of RTG-2 and CHSE-214 cells. Free Radic. Biol. Med. 28 1628-1637, 2000. 

Zafarullah, M., P.E. Olsson and L. Gedamu. Differential regulation of metallothionein genes in rainbow trout fibroblasts, RTG-2. Biochim. Biophys. Acta 1049 318-323, 1990. 

Tashiro-Itoh, T., Ichida, T. and Matsuda, Y. (1997). Metallothionein expression and concentration of copper and zinc are associated with tumar differentiation in hepatocellular carcinoma, Liver, 17, pp. 300-306. 

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