Skip to main content
Log in

Effects of cadmium on human platelet reactions

  • Original Investigations
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Human platelets incubated with Cd2+ took up the cation slowly, and the uptake was speeded up by ionophore A23187. The capacity of human platelets to accumulate Cd2+ was large, equivalent to 10 nmol Cd2+ per mg protein. The effects of Cd2+ on protein phosphorylation and serotonin release of human platelets were studied. Washed platelets incubated with Cd2+ showed a general increase in protein phosphorylation concurrent with a slow release of serotonin. In the presence of ionophore A23187, however, Cd2+ had a biphasic effect on protein phosphorylation: stimulatory at low and inhibitory at high Cd2+ concentrations. The phosphorylation of two proteins with molecular masses close to 43 and 20 kDa was more sensitive to the inhibitory effect of Cd2+, and under similar conditions, the primary effect of Cd2+ on serotonin release was inhibitory, although at lower Cd2+ concentrations a slight stimulation was noted. Thrombin increased the phosphorylation of several proteins, and a prior incubation with Cd2+ further augmented that of a 20 kDa protein, but this treatment did not affect thrombin-induced serotonin release.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barfield KD, Bevan DR (1985) Fusion of phospholipid vesicles by Zn2+, Cd2+, and Mg2+. Biochem Biophys Res Commun 128: 389–395

    Google Scholar 

  • Berry JP (1972) Renal lesions caused by cadmium. Study with the electron microscope and with the electron probe micro-analyzer. Pathol Biol 20: 401–412

    Google Scholar 

  • Caprino L, Togna G, Togna AR (1979) Cadmium-induced platelet hypersensitivity to aggregating agents. Pharmacol Res Commun 11: 731–737

    Google Scholar 

  • Chao S-H, Suzuki Y, Zysk JR, Cheung WY (1984) Activation of calmodulin by various metal cations as a function of ionic radius. Mol Pharmacol 26: 75–82

    Google Scholar 

  • Frojmovic MM, Milton JG (1982) Human platelet size, shape, and related functions in health and disease. Physiol Rev 62: 185–261

    Google Scholar 

  • Gasiewicz TA, Smith JC (1976) Interaction of cadmium and selenium in rat plasma in vivo and in vitro. Biochim Biophys Acta 428: 113–122

    Google Scholar 

  • Gerrard JM, Peterson DA, While JG (1981) Calcium mobilisation. In: Gordon JL (ed) Platelets in biology and pathology 2nd ed. Elsevier/-North-Holland Biomedical Press, Amsterdam pp 407–436

    Google Scholar 

  • Hathaway DR, Aldelstein RS (1979) Human platelet myosin light chain kinase requires the calcium-binding protein calmodulin. Proc Natl Acad Sci USA 76: 1653–1657

    Google Scholar 

  • Holme R, Sixma JJ, Murer EH, Hovig T (1973) Demonstration of platelet fibrinogen secretion via the surface connecting system. Thromb Res 3: 347–356

    Google Scholar 

  • Holmsen H, Dangelmaier CA (1981) Evidence that the platelet plasma membrane is impermeable to Ca2+ and Mg2+ complexes of A23187. J Biol Chem 256: 10449–10452

    Google Scholar 

  • Kawahara Y, Takai Y, Minakuchi R, Sano K, Nishizuka Y (1980) Phospholipid turnover as a possible transmembrane signal for protein phosphorylation during human platelet activation by thrombin Biochem Biophys Res Commun 97: 309–317

    Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685

    Google Scholar 

  • Lowry OH, Rosebrough NG, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275

    Google Scholar 

  • Matsubara-Khan J (1975) Critical organs and turnover characteristics of cadmium (Cd), selenium (Se), mercury (Hg), and chromium (Cr) in vivo. Jpn J Hyg 30: 91

    Google Scholar 

  • Mazzei GJ, Girard PR, Kuo JF (1984) Environmental pollutant Cd2+ biphasically and differentially regulates myosin light chain and phospholipid/Ca2+ -dependent protein kinase. FEBS Lett 173: 124–128

    Google Scholar 

  • Murer EH, Stewart GJ (1977) Insights into the mechanism of platelet action through studies at pH 5.3. Thromb Haemostas 38: 1018–1029

    Google Scholar 

  • Nishikawa M, Tanaka T, Hidaka H 61980) Ca2+-calmodulin-dependent phosphorylation and platelet secretion. Nature 287: 863–865

    Google Scholar 

  • Perry HM, Erlanger M (1971) Hypertension and tissue metal levels after intraperitoneal cadmium, mercury and zinc. Am J Physiol 220: 808–811

    Google Scholar 

  • Pfeiffer DR, Lardy HL (1976) Ionophore A23187; the effect of H+ concentrations on complex formation with divalent and monovalent cations and the demonstration ofU + transport in mitochondria mediated by A23187. Biochemistry 15: 935–943

    Google Scholar 

  • Rink TJ, Smith SW, Tsien RJ (1982) Cytoplasmic free Ca2+ in human platelet: Ca2+ thresholds and Ca2+-independent activation for shape-change and secretion. FEBS Lett 148: 21–26

    Google Scholar 

  • Rittenhouse SE (1984) Activation of human platelet phospholipase C by ionophore A23187 is totally dependent upon cyclooxigenase products and ADP. Biochem J 222: 103–110

    Google Scholar 

  • Samarawickrama GP (1979) Biological effects of cadmium in mammals. In: Webb, M (ed) Topics in Environmental Health, Vol 2. Elsevier/North-Holland Biomedical Press, New York pp 341–422

    Google Scholar 

  • Sano K, Takai Y, Yamanishi J, Nishizuka Y (1980) A role of calcium-activated phospholipid dependent protein kinase in human platelets activation. J Biol Chem 258: 2010–2013

    Google Scholar 

  • Schlaepfer WW (1971) Sequential study of endothelial changes in acute cadmium intoxication. Lab Invest 25: 556–564

    Google Scholar 

  • Suzuki Y, Chao S-H, Zysk JR, Cheung WY (1985) Stimulation of calmodulin by cadmium ion. Arch Toxicol 57: 205–211

    Google Scholar 

  • Touqui L, Rothhut B, Shaw AM, Fradin A, Vargattig BB, Russo-Marie F (1986) Platelet activation — a role for a 40K antiphospholipase A2 protein indistinguishable from lipocortin. Natur 321: 177–180

    Google Scholar 

  • Walsh PN, Gagnatelli G (1974) Platelet antiheparin activity: storage site and release mechanism. Blood 44: 157–165

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pezzi, L., Cheung, W.Y. Effects of cadmium on human platelet reactions. Arch Toxicol 61, 120–125 (1987). https://doi.org/10.1007/BF00661369

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00661369

Key words

Navigation