Intracellular cadmium

Squibb KS, Pritchard JB, Fowler BA. Cadmium metallothionein nephrotoxicity ultrastructural/biochemical alterations and intracellular cadmium-binding. J Pharmacol Exp Ther 1984 229 311-321. 

Brown, D.H., Avalos, A., 1993. The role of calcium in intracellular cadmium uptake by the lichen Peltigera membranacea. Ann. Bot. (Lond.) 71, 467 73,... 

Silar P, Butler G, Thiele DJ (1991) Heat shock transcription factor activates transcription of the yeast metallothionein gene. Mol Cell Biol 11 1232-1238 Squibb KS, Pritchard JB, Fowler BA (1984) Cadmium metallothionein nephropathy ultrastructural/biochemical alterations and intracellular cadmium binding. J Pharmacol Exp Ther 229 311-321... 

Hinkle, P. M. Shanshala, E. D., II Nelson, E. J. Measurement of intracellular cadmium with fluorescent dyes. Further evidence for the role of calcium channels in cadmium uptake. J. Biol Chem. 1992, 267, 25553-25559. 

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). 

Bordin, G., J. McCourt, and A. Rodriguez. 1994. Trace metals in the marine bivalve Macoma balthica in the Westerschelde estuary, the Netherlands. Part 2 intracellular partitioning of copper, cadmium, zinc and iron — variations of the cytoplasmic metal concentrations in natural and in vitro contaminated clams. Sci. Total Environ. 151 113-124. 

Depletion of ATP will also lead to a rise in intracellular Ca2+, presumably as a result of the reduction in activity of the ATPases and a reduction in other metabolic activity. The cytosolic free calcium may also rise because of release from mitochondrial stores as caused by cadmium, MPTP, and uncouplers. It seems that the crucial event is a sustained rise in cytosolic free calcium, and there are various consequences that arise from this event ... 

Chrestensen CA, Starke DW, Mieyal JJ. 2000. Acute cadmium exposure inactivates thioltransferase (Glutaredoxin), inhibits intracellular reduction of protein-glutathio-nyl-mixed disulfides, and initiates apoptosis. J Biol Chem 275 26556-26565. 

Metallothionein proteins are the most abundant intracellular, metal-binding proteins (Andrews, 2000). Four metallothionein isoforms have been identified in the mouse (MT-I-MT-IV) and are clustered within 50 kilobases of each other. In humans, there is one MTII gene and a cluster of MT I genes on chromosome 16 (Searl et al., 1984 West et al., 1990 Heuchel et al., 1995). The mammalian metallothioneins generally consist of 61 amino acids and 20 of these are cysteines (Heuchel et al., 1995). These cysteines are important for the binding of such bivalent metal ions, such as zinc, copper and cadmium. 

S. Keyhani, J. L. Lopez, D. S. Clark and J. D. Keasling (1996). Intracellular polyphosphate content and cadmium tolerance in Anacystis nidulans R2. Microbios, 88, 105-114. 

Metallothioneins (MTs) are a superfamily of low-molecular-weight (<7000-dalton) intracellular metal-binding proteins, which, in many species, play a critical role in (a) the detoxification of nonessential metals such as Cd2+ and Hg2+ and (b) the regulation of intracellular concentrations of essential metals such as Zn2+ and Cu+. In 1957, Kagi and Vallee first purified and characterized MT as a cadmium-binding protein in equine kidney. 

Klaassen, C. D., Liu, J., and Choudhuri, S. Metallothionein An intracellular protein to protect against cadmium toxicity. Annu. Rev. Pharmacol. Toxicol. 39, 267-294,1999. 

F5. Figueiredo-Pereira, M. E., Yakushin, S., and Cohen, G., Disruption of the intracellular sulfhydryl homeostasis by cadmium-induced oxidative stress leads to protein thiolation and ubiquitination in neuronal cells. J. Biol. Chem. 273, 12703-12709 (1998). 

The metabolism of zinc is influenced by hormones, stress situations, lipopolysaccharides, toxins, oxygen radicals, lipid peroxidations, etc. This may lead to fluctuations in the zinc concentration, mainly due to the induction of metallothioneine (MT), which is a transport and intracellular depot protein. One third of this protein consists of cysteine, which binds zinc, copper, cadmium, cobalt and mercury. This protects the body from toxic heavy metal... 

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