Cadmium-induced protein expression

Cadmium occurs only in one valency state (2 ) and does not form stable alkyl compounds or other organometallic compounds of known toxicological significance. Cadmium initially is distributed to the liver and then redistributes slowly to the kidney as cadmium-metallothionein (Cd-MT), with 50% of the total-body burden in the liver and kidney after distribution. Cadmium and several other metals induce the expression of metallothionein, a cysteine-rich protein with high affinity for metals such as cadmium and zinc. Metallothionein protects cells against cadmium toxicity by preventing the interaction of cadmium with other proteins. 

Isolated rat type II lung cells were more sensitive than Clara cells to cadmium-induced apoptosis and cell viability (LIg et al. 2002). On exposure to 10 jUmol/1 cadmium acetate, the levels of the apoptosis-modulating proteins p53 and Bax were increased at 2 h and 5-12 h, respectively. The expression of p53 preceded the expression of Bax and the apoptotic process. The exposure to 10/ nol/l cadmium acetate did not significantly increase the formation of cellular reactive oxygen species. However, after the exposure to a high concentration of cadmium acetate (100/anol/1), a 30% increase of the reactive oxygen species level was observed. Catalase, superoxide dismutase, dimethyl sulphoxide, or tetramethylthiourea did not protect against cadmium-induced apoptosis. 

Metallothionein expression is mainly regulated at the transcriptional level and is induced by various heavy metals, such as zinc. There are seven short sequence motifs located in a region within 200 base pairs upstream of the transcription start site. These cis-acting DNA elements are responsible for heavy metal induction and are thus termed metal responsive elements (MREs) (Stuart et al., 1984). Several regulatory proteins have been cloned which interact with these MREs. One of these, MRE-binding transcription factor-1 (MTF-1), is essential for the transcriptional activation of metallothionein genes by heavy metals like zinc and cadmium (Radtke et al., 1993 Palmiter, 1994 Heuchel et al., 1994 Koiszumi et al., 1999). 

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. 

Initial studies of proteome responses to environmental chemicals in soil-dwelling animals or plants are currently under way. Kuperman et al. (2004) have used the approach to identify differentially expressed proteins in earthworms exposed to chemical warfare agents. Toxicological studies also have been undertaken. Vido et al. (2001) analysed yeast cells exposed to an acute cadmium stress 54 proteins were induced and 43 repressed. Finally, Bradley (2000) used two-... 

Data generated from a study of lead-induced synthesis of stress proteins illustrated that different metals have both common and individual effects on expression of stress proteins. Lead-induced stress protein synthesis was unusual in that it did not share the properties of metals, such as cadmium and arsenite, to mimic the effects of heat (Shelton et al. 1986). Rather, lead induced two minor classes of proteins. In this study, exposure of primary rat kidney epithelial cells and rat fibroblasts to lead glutamate induced synthesis of two grps and a protein of 32 kDa, which was shown to... 

Courgeon A-M, Maisonhaute C, Best-Belpomme M (1984) Heat shock proteins are induced by cadmium in Drosophila cells. Exp Cell Res 153 515-521 Darasch S, Mosser DD, Bols NC, Heikkila JJ (1988) Heat shock gene expression on Xenopus laevis A6 cells in response to heat shock and sodium arsenite treatments. Biochem Cell Biol 66 862-870... 

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