Disease relevance of cadmium

• Whilst iron (Fe), copper (Cu), chromium (Cr), vanadium (V) and cobalt (Co) undergo redox-cycling reactions, for a second group of metals, mercury (Hg), cadmium (Cd) and nickel (Ni), the primary route for their toxicity is depletion of glutathione and bonding to sulfhydryl groups of proteins [1].
• The main symptoms of Cd nephrotoxicity, including polyuria, phosphaturia, aminoaciduria, glucosuria, and proteinuria, suggest that various brush-border membrane (BBM) transporters are the main targets of Cd [2].
• In Brazito soil, dual inoculation with a Cd-resistant bacterium plus a known 2,4-D-degrading bacterium, Ralstonia eutropha JMP134, enhanced 2,4-D degradation [3].
• Chronic exposure to Cd causes loss of bone mass and increased incidence of bone fractures, as seen in Itai-itai patients and laboratory animals [4].
• Acute exposure to Cd (2.0 mg l(-1) for 48 h) caused metal granule accumulation along cells lining the tubular lumen and cellular dissociation, with acidosis and necrosis in the cytoplasm and Cd deposits in mitochondria [5].

Psychiatry related information on cadmium

• Chronic exposure to Cd induced increased fatigue and mild uncoordinated motor activity [6].
• The risk assessment results implicate exposure to waterborne Cu and Cd may pose no significant risk to clam valve activity in the short-time response periods (e.g., <30 min), yet a relative high risk for valve closure response to waterborne Cu at response times greater than 120 min is alarming [7].

High impact information on cadmium

• The capacity for detoxification and internal storage of Cd resulted in a strong potential for trophic transfer of Cd through the aquatic food web [8].
• Several derivative cell lines expressing inducible v-rasH manifested hormone-independent growth in culture when treated with 10(-7) M Cd2+ . Cd2+ induction of v-rasH p21 was also shown to increase anchorage-independent colony formation of the v-rasH-expressing cell lines tested [9].
• We found that AtATM3-overexpressing plants were enhanced in resistance to Cd, whereas atatm3 mutant plants were more sensitive to Cd than their wild-type controls [10].
• In conclusion, our data show that AtATM3 contributes to Cd resistance and suggest that it may mediate transport of glutamine synthetase-conjugated Cd(II) across the mitochondrial membrane [10].
• Moreover, the transgenic protoplasts showed lower accumulation of Cd and faster release of preloaded Cd than wild-type protoplasts [11].

Chemical compound and disease context of cadmium

• We have used the housefly, Musca domestica, as a model organism to study the toxicity of four heavy metals: copper (Cu), zinc (Zn), cadmium (Cd), and lead (Pb) [12].
• Cadmium (Cd), cobalt (Co), and molybdenum (Mo) were least in amount in renal papilla as compared with the cortex and medulla in renal stone kidney [13].
• Presently FAO/WHO Expert Committee on Food Additives and Food has a PTWI (provisional tolerable weekly intake) value for adult persons of 7 microg/kg body weight for Cd (WHO 2003) a value corresponding to 1 microg/kg body weight for each day of a week [14].

Biological context of cadmium

• Six clones of DNA repair deficient cells and five clones of DNA repair proficient cells have been isolated which express Cd inducible CYP1A1 [15].
• 5. At 10 microM Cd2+ produced a 43 +/- 6% (n = 3) block of the inward current at 0 mV when Ca2+ (7.5 mM) was the charge carrier (ICa), compared with the 36 +/- 3% block of IBa induced by 1 microM-Cd2+, consistent with the suggestion that Ca2+, Ba2+ and Cd2+ compete for the same binding site [16].
• We have recently proposed that Cd may impair the vesicle-dependent recycling of BBM transporters by inhibiting vacuolar H+-ATPase (V-ATPase) activity and endocytosis in PT cells (Herak-Kramberger CM, Sabolic I, and Brown D [2].
• Transductional analysis revealed that the 37S plasmid in S6 encoded for cadmium resistance (Cad) but not SEB [17].
• SAHP cells had a spike duration of 1.4 ms and a prominent shoulder on the falling phase of the SAHP cell action potentials that was reduced by Cd2+ [18].

Anatomical context of cadmium

• Numerous derivative cell lines were isolated which manifested inducible expression of rasH p21 protein when the cells were treated with Cd2+ [9].
• In the oviduct, only isthmus epithelial cells responded to metals (Zn or Cd) by increased accumulation of this mRNA [19].
• These results were correlated with the effects of transient exposure to high levels of metals (zinc (Zn) or cadmium (Cd] on the continued development of preimplantation embryos into blastocysts in culture [19].
• These processes may lead to a time-dependent loss of cell membrane components, resulting in reabsorptive and secretory defects that occur in Cd-induced nephrotoxicity [2].
• A deficiency of MTs in the testis was originally suspected on the basis of amino acid composition analysis, since MT-like proteins isolated as Cd-binding proteins did not have a characteristic MT structure [20].

Associations of cadmium with other chemical compounds

• These observations are consistent with a model in which expression of an Arabidopsis-gene-encoded, Cd(2+)-efficient antiporter in host plant roots results in greater root vacuole Cd(2+) transport activity, increased root Cd accumulation, and a shift in overall root tonoplast ion transport selectivity towards higher Cd(2+) selectivity [21].
• Both Zn (200 mu m) and Cd (0.1 mu m), but not Mn, induced the synthesis of metallothionein [22].
• Gamete exposure to increasing metal concentrations resulted in a significant decrease of the percentage of normally hatched larvae, showing median effective concentrations (EC50) of 721 microg/L (6.42 microM) for Cd, 12772 microg/L (226 microM) for Cr, 36.6 microg/L (0.576 microM) for Cu, and 44.7 microg/L (0.223 microM) for Hg [23].
• Batch sorption isotherms for nickel (Ni), copper (Cu), and cadmium (Cd) showed that the pure culture of N. amarae exhibited significantly higher metal sorption capacity than the activated sludge biomass obtained from Wilmington Wastewater Treatment Plant (Wilmington, DE) [24].
• Concentrations of 11 metals (cadmium [Cd], lead [Pb], copper [Cu], iron [Fe], manganese [Mn], cobalt [Co], chromium [Cr], nickel [Ni], zinc [Zn], magnesium [Mg], and calcium [Ca]) and protein in human pancreatic juice were studied [25].

Gene context of cadmium

• Surprisingly, the appearance of metal responsiveness of the MT genes during development correlated with decreased Zn toxicity and increased Cd toxicity; two-cell embryos were Zn-sensitive and Cd-resistant, whereas eight-cell and older embryos were Zn-resistant and Cd-sensitive [19].
• Benzo[a]pyrene-trans-7,8-diol (BPD) is cytotoxic in Cd induced CYP1A1 expressing cells [15].
• Morphological evaluations revealed that Cd or Zn preincubation led to relative preservation of MAP2 staining and GFAP [26].
• Moreover, atatm3 mutant plants expressing 35S promoter-driven AtATM3 were more resistant to Cd than wild-type plants [10].
• BPD is cytotoxic to Cd induced CYP1A1 expressing XPA cells at > 10-fold lower doses than it is to Cd induced CYP1A1 expressing DNA repair normal cells [15].

Analytical, diagnostic and therapeutic context of cadmium

• To confirm that MT-1 and MT-2 are present in the rat testis, we purified and isolated Cd-binding proteins by homogenization using Cd-containing buffer, followed by sequential purification using Sephadex G-75 gel filtration chromatography and anion HPLC column chromatography, which yielded Cd-binding protein-1 (Cd-BP-1) and -2 (Cd-BP-2) [20].
• A Zn-, Cd-binding protein fraction in the low-molecular-weight range was seen by gel filtration in cytosol from either dorsal prostate (DP) or VP [27].
• Cadmium (Cd2+) disrupts Ca(2+)-dependent cell-cell junctions and alters the pattern of E-cadherin immunofluorescence in LLC-PK1 cells [28].
• Metal concentrations in benthic invertebrates reflected differences in feeding habits and body size among taxa, with greatest concentrations of Zn, Cu, and Cd in the small mayfly Rhithrogena, which feeds on periphyton, and greatest concentrations of Pb in the small stonefly Zapada, a detritivore [29].
• Real-time RT-PCR of a reference culture and tolerant populations revealed significant gene responses upon Cd exposure [30].

References