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Chemical Compound Review

Cadmium ion     cadmium(+2) cation

Synonyms: Cadmium(2+), Cadmium Atom, Cadmium ions, Cd+2, Cd2+, ...
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Disease relevance of CADMIUM

  • Whereas it is the major determinant of Listeria resistance to Cd(2+), CadA expressed in Saccharomyces cerevisiae severely decreases yeast tolerance to Cd(2+) (Wu, C. C., Bal, N., P??rard, J., Lowe, J., Boscheron, C., Mintz, E., and Catty, P. (2004) Biochem. Biophys. Res. Commun. 324, 1034-1040) [1].
  • An extensive search for DeltahscC phenotypes revealed a hypersensitivity to Cd(2+) ions and UV irradiation, suggesting roles of HscC in the cellular response to these stress treatments [2].
  • Here, we describe the effects of Zn(2+) on complex I to define whether complex I may contribute to mediating the pathological effects of zinc in states such as ischemia and to determine how Zn(2+) can be used to probe the mechanism of complex I. Zn(2+) inhibits complex I more strongly than Mg(2+), Ca(2+), Ba(2+), and Mn(2+) to Cu(2+) or Cd(2+) [3].
  • Oligodendrocyte progenitors were more vulnerable to Cd(2+) toxicity than were mature oligodendrocytes [4].
  • Crystals of DAHPS from Thermotoga maritima (DAHPS(Tm)) were grown in the presence of PEP and metal cofactor, Cd(2+), and then soaked with E4P at 4 degrees C where the catalytic activity of the enzyme is negligible [5].

High impact information on CADMIUM

  • RESULTS: A basolateral membrane conductance with the characteristics of ClC-2 channels, including Cd(2+) sensitivity, selectivity, and inhibition by extracellular alkalinization, is present in distal colon epithelium [6].
  • Upon Cd(2+) binding, we observed the release of two protons from His-H126/128 at the Cd(2+) binding site and significant pK(a) shifts for residues along the PT pathways [7].
  • The structures were refined to R factors of 23% and 24% for the Cd(2+) and Zn(2+) complexes, respectively [8].
  • In addition to the changes in the kinetics, a structural effect of Cd(2+) on Glu-H173 was observed [8].
  • Finally, analysis of the role of Cd(2+) in the phosphorylation from ATP and from P(i) of the mutants suggests that two Cd(2+) ions are involved in the reaction cycle of CadA [1].

Chemical compound and disease context of CADMIUM

  • This includes the complexes of the E. coli enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures reported for the human Zn(2+) enzyme [9].
  • The facts that the CaR is a promiscuous polycation sensor and that the effects of these ions are additive to activate it suggest that the CaR may contribute to the toxicity of some heavy metals such as Pb(2+), Cd(2+), Co(2+), and Fe(2+) for the kidney and other tissues where it is expressed [10].
  • When synaptic transmission was blocked by the addition of Cd(2+) to the Ringer, application of kainate directly to ganglion cells evoked excitatory currents that were strongly blocked by GYKI52466 [11].
  • Finally, a robust nimodipine-sensitive Cd(2+) influx was observed using a low extracellular Cd(2+) concentration (5 muM) in neurons and testicular slice cultures, attesting to the relevance of the LTCC pathway to heavy metal toxicity [12].
  • Escherichia coli cells expressing the TrxABjMT2 fusion were more tolerant to Cu(2+) and Cd(2+) exposure than control strains [13].

Biological context of CADMIUM

  • Endocytosis appears qualitatively normal in luv1 mutants, but some portion (28%) of carboxypeptidase Y is secreted. luv1 mutants are sensitive to several ions (Zn(2+), Mn(2+), and Cd(2+)) and to pH extremes [14].
  • Our data clearly show that As(3+)-, Cd(2+)-, and Cr(6+)-induced oxidative stress modulates Cyp1a1 at transcriptional and posttranscriptional levels but induces Nqo1 and Gst ya at the transcriptional level [15].
  • Cd(2+) induces apoptosis of kidney proximal tubule (PT) cells [16].
  • Using the model neurosecretory cell line, PC12, we have shown that AbetaPs cause enhancement of evoked exocytosis via formation of a Cd(2+) -resistant Ca(2+) influx pathway, and also cause selective, functional up-regulation of current through L-type Ca(2+) channels [17].
  • Nicotine-evoked exocytosis was entirely dependent on extracellular Ca(2+) but was only partly blocked by Cd(2+), a nonselective blocker of voltage-gated Ca(2+) channels [18].

Anatomical context of CADMIUM

  • Also, these observations indicate that Cd(2+) ions exert their toxic effects on cellular metabolism in the ER rather than in the cytosol [19].
  • Similar to the alkaline earth metal ions, application of Cd(2+) elicited inward current in CaT2-expressing oocytes with a K(m) of 1.3 mm [20].
  • Taken together, these results are consistent with state-dependent accessibility of single Cd(2+) ions to coordination sites within a relatively narrow inner vestibule [21].
  • The intrinsic optical response was mostly eliminated by Cd(2+), suggesting that the detected signals were mainly mediated by postsynaptic mechanisms activated by sensory nerve fibers [22].
  • Cd(2+) uptake by the MT(-/-) parental cell line was independent of sodium, energy, and electrogenic potential [23].

Associations of CADMIUM with other chemical compounds

  • Lysosomal involvement in hepatocyte cytotoxicity induced by Cu(2+) but not Cd(2+) [24].
  • Coexpression of a cysteine-substituted KCNE1 (F54C) with V319Y significantly increases the sensitivity of channels to external Cd(2+), but neither the extent of nor the kinetics of the onset of (or the recovery from) Cd(2+) block was affected by [TEA(+)](o) at 10x the IC(50) for channel block [25].
  • Mature oligodendrocytes accumulated relatively higher levels of Cd(2+) than did progenitors, as determined by (109)CdCl(2) uptake; treatment with the metal ion caused a more pronounced reduction in intracellular glutathione levels and significantly higher free radical accumulation in progenitors [4].
  • In the following it is shown that hepatocyte cytotoxicity induced by Cu(2+), but not Cd(2+), was preceded by lysosomal membrane damage as demonstrated by acridine orange release [24].
  • Incubation of membranes from the expression strain with [gamma-(33)P]ATP in the presence of Zn(2+), Cd(2+), or Pb(2+) brings about phosphorylation of two membrane proteins with molecular masses of approximately 90 and 190 kDa, most likely representing the ZntA monomer and dimer, respectively [26].

Gene context of CADMIUM

  • These data strongly suggest that access of Cd(2+) to the cysteine-mutated site on KCNE1 is independent of pore occlusion caused by TEA(+) binding to the outer region of the KCNE1/V319Y pore, and that KCNE1 does not reside within the pore region of the assembled channels [25].
  • In the present study, we evaluated the role of As(3+)-, Cd(2+)-, and Cr(6+)-induced oxidative stress on the expression of Cyp1a1, Nqo1, and Gst ya in Hepa 1c1c7 cells [15].
  • Ion selectivity of transport in root-tonoplast vesicles isolated from FS3::CAX4-expressing plant lines having a range of gene expression was Cd(2+)>Zn(2+)>>Ca(2+)>>Mn(2+) and the ratios of maximal Cd(2+) (and Zn(2+)) versus maximal Ca(2+) and Mn(2+) transport were correlated with the levels of CAX4 expression [27].
  • Concomitantly, MT1 protein levels in MTF1dko7 cells were inducible to the same degree as that in Hepa-1 cells when treated with Zn(2+), but not with Cd(2+) [28].
  • First, Cd(2+) block of MinK-55C channels formed with wild-type KCNQ1 is shown to depend not only on voltage and trans-ions but state (showing decreased on-rate with increased open time and blocker trapping on channel closure) [29].

Analytical, diagnostic and therapeutic context of CADMIUM

  • Northern blot analysis showed that MTT1 mRNA is not detectable in the absence of Cd(2+), is induced within 10 min of its addition, is expressed in proportion to its concentration, and rapidly disappears upon its withdrawal [30].
  • In this study, we report structural, vibrational, and magnetic data providing evidence of random ion displacement in the core of CdSe quantum dots on the Cd(2+) sites by Co(2+) ions (between x = 0 and 0.30) [31].
  • The titration data indicated that VP9 binds with both Zn(2+) and Cd(2+) [32].
  • The position of the Zn(2+)-binding site that is essential for catalysis was inferred from the positions of bound Cd(2+) ions, which were part of the crystallization medium [33].
  • Stability of iron ligation was measured by temperature-ramp and fixed-temperature time course experiments, monitoring iron release in both the absence and presence of more thiophilic metals (Zn(2+), Cd(2+)) and over a range of pH values [34].


  1. The Cadmium Transport Sites of CadA, the Cd2+-ATPase from Listeria monocytogenes. Wu, C.C., Gardarin, A., Martel, A., Mintz, E., Guillain, F., Catty, P. J. Biol. Chem. (2006) [Pubmed]
  2. Structure-function analysis of HscC, the Escherichia coli member of a novel subfamily of specialized Hsp70 chaperones. Kluck, C.J., Patzelt, H., Genevaux, P., Brehmer, D., Rist, W., Schneider-Mergener, J., Bukau, B., Mayer, M.P. J. Biol. Chem. (2002) [Pubmed]
  3. The Inhibition of Mitochondrial Complex I (NADH:Ubiquinone Oxidoreductase) by Zn2+. Sharpley, M.S., Hirst, J. J. Biol. Chem. (2006) [Pubmed]
  4. Exposure of developing oligodendrocytes to cadmium causes HSP72 induction, free radical generation, reduction in glutathione levels, and cell death. Almazan, G., Liu, H.N., Khorchid, A., Sundararajan, S., Martinez-Bermudez, A.K., Chemtob, S. Free Radic. Biol. Med. (2000) [Pubmed]
  5. Crystal structure of the reaction complex of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase from Thermotoga maritima refines the catalytic mechanism and indicates a new mechanism of allosteric regulation. Shumilin, I.A., Bauerle, R., Wu, J., Woodard, R.W., Kretsinger, R.H. J. Mol. Biol. (2004) [Pubmed]
  6. Basolateral ClC-2 chloride channels in surface colon epithelium: regulation by a direct effect of intracellular chloride. Catalán, M., Niemeyer, M.I., Cid, L.P., Sepúlveda, F.V. Gastroenterology (2004) [Pubmed]
  7. Induced conformational changes upon Cd2+ binding at photosynthetic reaction centers. Ishikita, H., Knapp, E.W. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Determination of the binding sites of the proton transfer inhibitors Cd2+ and Zn2+ in bacterial reaction centers. Axelrod, H.L., Abresch, E.C., Paddock, M.L., Okamura, M.Y., Feher, G. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  9. Determination of the structure of Escherichia coli glyoxalase I suggests a structural basis for differential metal activation. He, M.M., Clugston, S.L., Honek, J.F., Matthews, B.W. Biochemistry (2000) [Pubmed]
  10. Extracellular Ca(2+)-sensing receptor is a promiscuous divalent cation sensor that responds to lead. Handlogten, M.E., Shiraishi, N., Awata, H., Huang, C., Miller, R.T. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  11. Light-evoked excitatory synaptic currents of X-type retinal ganglion cells. Cohen, E.D. J. Neurophysiol. (2000) [Pubmed]
  12. Silencing of ZnT-1 expression enhances heavy metal influx and toxicity. Ohana, E., Sekler, I., Kaisman, T., Kahn, N., Cove, J., Silverman, W.F., Amsterdam, A., Hershfinkel, M. J. Mol. Med. (2006) [Pubmed]
  13. Expression of BjMT2, a metallothionein 2 from Brassica juncea, increases copper and cadmium tolerance in Escherichia coli and Arabidopsis thaliana, but inhibits root elongation in Arabidopsis thaliana seedlings. Zhigang, A., Cuijie, L., Yuangang, Z., Yejie, D., Wachter, A., Gromes, R., Rausch, T. J. Exp. Bot. (2006) [Pubmed]
  14. Luv1p/Rki1p/Tcs3p/Vps54p, a yeast protein that localizes to the late Golgi and early endosome, is required for normal vacuolar morphology. Conboy, M.J., Cyert, M.S. Mol. Biol. Cell (2000) [Pubmed]
  15. The role of oxidative stress in the modulation of aryl hydrocarbon receptor-regulated genes by As3+, Cd2+, and Cr6+. Elbekai, R.H., El-Kadi, A.O. Free Radic. Biol. Med. (2005) [Pubmed]
  16. Cd(2+)-induced cytochrome c release in apoptotic proximal tubule cells: role of mitochondrial permeability transition pore and Ca(2+) uniporter. Lee, W.K., Bork, U., Gholamrezaei, F., Thévenod, F. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  17. Divergent pathways account for two distinct effects of amyloid beta peptides on exocytosis and Ca(2+) currents: involvement of ROS and NF-kappaB. Green, K.N., Peers, C. J. Neurochem. (2002) [Pubmed]
  18. Three distinct Ca(2+) influx pathways couple acetylcholine receptor activation to catecholamine secretion from PC12 cells. Taylor, S.C., Peers, C. J. Neurochem. (2000) [Pubmed]
  19. A transporter in the endoplasmic reticulum of Schizosaccharomyces pombe cells mediates zinc storage and differentially affects transition metal tolerance. Clemens, S., Bloss, T., Vess, C., Neumann, D., Nies, D.H., Zur Nieden, U. J. Biol. Chem. (2002) [Pubmed]
  20. A rat kidney-specific calcium transporter in the distal nephron. Peng, J.B., Chen, X.Z., Berger, U.V., Vassilev, P.M., Brown, E.M., Hediger, M.A. J. Biol. Chem. (2000) [Pubmed]
  21. Structure and dynamics of the pore of inwardly rectifying K(ATP) channels. Loussouarn, G., Makhina, E.N., Rose, T., Nichols, C.G. J. Biol. Chem. (2000) [Pubmed]
  22. Optical imaging of intrinsic signals induced by peripheral nerve stimulation in the in vivo rat spinal cord. Sasaki, S., Yazawa, I., Miyakawa, N., Mochida, H., Shinomiya, K., Kamino, K., Momose-Sato, Y., Sato, K. Neuroimage (2002) [Pubmed]
  23. Acquired cadmium resistance in metallothionein-I/II(-/-) knockout cells: role of the T-type calcium channel Cacnalpha1G in cadmium uptake. Leslie, E.M., Liu, J., Klaassen, C.D., Waalkes, M.P. Mol. Pharmacol. (2006) [Pubmed]
  24. Lysosomal involvement in hepatocyte cytotoxicity induced by Cu(2+) but not Cd(2+). Pourahmad, J., Ross, S., O'Brien, P.J. Free Radic. Biol. Med. (2001) [Pubmed]
  25. TEA(+)-sensitive KCNQ1 constructs reveal pore-independent access to KCNE1 in assembled I(Ks) channels. Kurokawa, J., Motoike, H.K., Kass, R.S. J. Gen. Physiol. (2001) [Pubmed]
  26. Expression and mutagenesis of ZntA, a zinc-transporting P-type ATPase from Escherichia coli. Okkeri, J., Haltia, T. Biochemistry (1999) [Pubmed]
  27. Enhanced Cd(2+)-selective root-tonoplast-transport in tobaccos expressing Arabidopsis cation exchangers. Koren'kov, V., Park, S., Cheng, N.H., Sreevidya, C., Lachmansingh, J., Morris, J., Hirschi, K., Wagner, G.J. Planta (2007) [Pubmed]
  28. Retrovirally expressed metal response element-binding transcription factor-1 normalizes metallothionein-1 gene expression and protects cells against zinc, but not cadmium, toxicity. Solis, W.A., Childs, N.L., Weedon, M.N., He, L., Nebert, D.W., Dalton, T.P. Toxicol. Appl. Pharmacol. (2002) [Pubmed]
  29. Pore- and state-dependent cadmium block of I(Ks) channels formed with MinK-55C and wild-type KCNQ1 subunits. Chen, H., Sesti, F., Goldstein, S.A. Biophys. J. (2003) [Pubmed]
  30. A robust inducible-repressible promoter greatly facilitates gene knockouts, conditional expression, and overexpression of homologous and heterologous genes in Tetrahymena thermophila. Shang, Y., Song, X., Bowen, J., Corstanje, R., Gao, Y., Gaertig, J., Gorovsky, M.A. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  31. Magnetic ordering in doped Cd(1-x)Co(x)Se diluted magnetic quantum dots. Hanif, K.M., Meulenberg, R.W., Strouse, G.F. J. Am. Chem. Soc. (2002) [Pubmed]
  32. Identification of a Novel Nonstructural Protein, VP9, from White Spot Syndrome Virus: Its Structure Reveals a Ferredoxin Fold with Specific Metal Binding Sites. Liu, Y., Wu, J., Song, J., Sivaraman, J., Hew, C.L. J. Virol. (2006) [Pubmed]
  33. Crystal structure of Methanobacterium thermoautotrophicum phosphoribosyl-AMP cyclohydrolase HisI. Sivaraman, J., Myers, R.S., Boju, L., Sulea, T., Cygler, M., Jo Davisson, V., Schrag, J.D. Biochemistry (2005) [Pubmed]
  34. Contribution of the [FeII(SCys)4] site to the thermostability of rubredoxins. Bonomi, F., Eidsness, M.K., Iametti, S., Kurtz, D.M., Mazzini, S., Morleo, A. J. Biol. Inorg. Chem. (2004) [Pubmed]
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