BioMetals

, Volume 22, Issue 2, pp 261–274

Hg2+ and Cd2+ interact differently with biomimetic erythrocyte membranes

  • Mary Trang Le
  • Jürgen Gailer
  • Elmar J. Prenner
Article

Abstract

In order to characterize the potentially deleterious effects of toxic Hg2+ and Cd2+ on lipid membranes, we have studied their binding to liposomes whose composition mimicked erythrocyte membranes. Fluorescence spectroscopy utilizing the concentration dependent quenching of Phen Green™ SK by Hg2+ and Cd2+ was found to be a sensitive tool to probe these interactions at metal concentrations ≤1 μM. We have systematically developed a metal binding affinity assay to screen for the interactions of Hg2+ or Cd2+ with certain lipid classes. A biomimetic liposome system was developed that contained four major lipid classes of erythrocyte membranes (zwitterionic lipids: phosphatidylcholine and phosphatidylethanolamine; negatively charged: phosphatidylserine and neutral: cholesterol). In contrast to Hg2+, which preferentially bound to the negatively charged phosphatidylserine compared to the zwitterionic components, Cd2+ bound stronger to the two zwitterionic lipids. Thus, the observed distinct differences in the binding affinity of Hg2+ and Cd2+ for certain lipid classes together with their known effects on membrane properties represent an important first step toward a better understanding the role of these interactions in the chronic toxicity of these metals.

Keywords

Toxic metals Hg2+ Cd2+ Liposomes Model systems Membranes Lipids Erythrocytes Fluorescence spectroscopy 

Abbreviations

POPC

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine

POPE

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine

POPS

1-Palmitoyl-2-oleoyl-sn-glycero-3-[phospho-l-serine]

PC

Phosphatidylcholine

PE

Phosphatidylethanolamine

PS

Phosphatidylserine

Chol

Cholesterol

PGSK

Phen Green™ SK

References

  1. Akahori A, Jozwiak A, Gabryelak T, Gondko R (1999) Effect of zinc on carp (Cyprinus carpio L.) erythrocytes. Comp Biochem Physiol 123(Part C):209–215. doi:10.1016/S0305-0491(99)00063-2 Google Scholar
  2. Allen TM, Hong K, Papahadjopoulos D (1990) Membrane contact, fusion, and hexagonal (HII) transitions in phosphatidylethanolamine liposomes. Biochemistry 29:2976–2985. doi:10.1021/bi00464a013 PubMedCrossRefGoogle Scholar
  3. Berne BJ (2000) Dynamic light scattering: with applications to chemistry, biology and physics. Dover Publications, Mineola, pp 24–37Google Scholar
  4. Bevan DR, Worrell WJ, Barfield KD (1983) The Interaction of Ca2+, Mg2+, Zn2+, Cd2+, and Hg2+ with phospholipid bilayer vesicles. Colloids Surf 6:365–376. doi:10.1016/0166-6622(83)80027-4 CrossRefGoogle Scholar
  5. Bhattacharya S, Haldar S (2000) Interactions between cholesterol and lipids in bilayer membranes. Role of lipid headgroup and hydrocarbon chain-backbone linkage. Biochim Biophys Acta Biomembr 1467:39–53. doi:10.1016/S0005-2736(00)00196-6 CrossRefGoogle Scholar
  6. Block K (1985) Biochemistry of lipids and membranes. Benjamin/Cummins, Menlo ParkGoogle Scholar
  7. Clarkson TW, Magos L, Myers GJ (2003) The toxicology of mercury—current exposures and clinical manifestations. N Engl J Med 349:1731–1737. doi:10.1056/NEJMra022471 PubMedCrossRefGoogle Scholar
  8. Coonse KG, Coonts AJ, Morrison EV, Heggland SJ (2007) Cadmium induces apoptosis in the human osteoblast-like cell line Saos-2. J Toxicol Environ Health Part A Curr Issues 70:575–581CrossRefGoogle Scholar
  9. Counter SA, Buchanan LH (2004) Mercury exposure in children: a review. Toxicol Appl Pharmacol 198:209–230. doi:10.1016/j.taap.2003.11.032 PubMedCrossRefGoogle Scholar
  10. Deleers M, Servais JP, Wulfert E (1986) Neurotoxic cations induce membrane rigidification and membrane fusion at micromolar concentrations. Biochim Biophys Acta 855:271–276. doi:10.1016/0005-2736(86)90174-4 PubMedCrossRefGoogle Scholar
  11. Delnomdedieu M, Boudou A, Desmazes JP, Georgescauld D (1989) Interaction of mercury-chloride with the primary amine group of model membranes containing phosphatidylserine and phosphatidylethanolamine. Biochim Biophys Acta 986:191–199. doi:10.1016/0005-2736(89)90467-7 CrossRefGoogle Scholar
  12. Delnomdedieu M, Boudou A, Georgescauld D, Dufourc EJ (1992) Specific interactions of mercury-chloride with membranes and other ligands as revealed by mercury-NMR. Chem Biol Interact 81:243–269. doi:10.1016/0009-2797(92)90081-U PubMedCrossRefGoogle Scholar
  13. Eisele K, Lang PA, Kempe DS, Klarl BA, Niemoller O, Wieder T et al (2006) Stimulation of erythrocyte phosphatidylserine exposure by mercury ions. Toxicol Appl Pharmacol 210:116–122. doi:10.1016/j.taap.2005.07.022 PubMedCrossRefGoogle Scholar
  14. Forstner J, Manery JF (1971) Calcium binding by human erythrocyte membranes. Biochem J 124:563–571PubMedGoogle Scholar
  15. Foulkes EC (1996) Metals and biological membranes. In: Chang LW (ed) Toxicology of metals. CRC Lewis Publishers, New York, pp 133–143Google Scholar
  16. Gailer J (2002) Reactive selenium metabolites as targets of toxic metals/metalloids in mammals: a molecular toxicological perspective. Appl Organomet Chem 16:701–707. doi:10.1002/aoc.376 CrossRefGoogle Scholar
  17. Gailer J (2007) Arsenic–selenium and mercury–selenium bonds in biology. Coord Chem Rev 251:234–254. doi:10.1016/j.ccr.2006.07.018 CrossRefGoogle Scholar
  18. Garcia JJ, Martinez-Ballarin E, Millan-Plano SA, Albendea JL, Fuentes C, Escanero JF (2005) Effects of trace elements on membrane fluidity. J Trace Elem Med Biol 19:19–22. doi:10.1016/j.jtemb.2005.07.007 PubMedCrossRefGoogle Scholar
  19. Girault L, Lemaire P, Boudou A, Debouzy JC, Dufourc EJ (1996) Interactions of inorganic mercury with phospholipid micelles and model membranes. A P-31-NMR study. Eur Biophys J Biophys Lett 24:413–421Google Scholar
  20. Girault L, Boudou A, Dufourc EJ (1998) Cd-113-, P-31-NMR and fluorescence polarization studies of cadmium(II) interactions with phospholipids in model membranes. Biochim Biophys Acta Biomembr 1414:140–154. doi:10.1016/S0005-2736(98)00162-X CrossRefGoogle Scholar
  21. Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF (2007) Cadmium-induced cancers in animals and in humans. Int J Occup Environ Health 13:202–212PubMedGoogle Scholar
  22. Kirschner DA, Ganser AL (1982) Myelin labeled with mercuric chloride asymmetric localization of phosphatidylethanolamine plasmalogen. J Mol Biol 157:635–658. doi:10.1016/0022-2836(82)90503-4 PubMedCrossRefGoogle Scholar
  23. Kostka B (1991) Toxicity of mercury-compounds as a possible risk factor for cardiovascular-diseases. Br J Ind Med 48:845–846PubMedGoogle Scholar
  24. Kremer JMH, Esker MWJ, Pathmamanoharan C, Wiersema PH (1977) Vesicles of variable diameter prepared by a modified injection method. Biochemistry 16:3932–3935. doi:10.1021/bi00636a033 PubMedCrossRefGoogle Scholar
  25. Lakowicz JR (1999) Principles of fluorescence spectroscopy. Plenum, New York, pp 237–289Google Scholar
  26. Lau S, Sarkar B (1979) Inorganic mercury(II)-binding components in normal human-blood serum. J Toxicol Environ Health 5:907–916PubMedCrossRefGoogle Scholar
  27. Lee WK, Torchalski B, Thevenod F (2007) Cadmium-induced ceramide formation triggers calpain-dependent apoptosis in cultured kidney proximal tubule cells. Am J Physiol Cell Physiol 293:C839–C847. doi:10.1152/ajpcell.00197.2007 PubMedCrossRefGoogle Scholar
  28. Lis LJ, Lis WT, Parsegian VA, Rand RP (1981) Adsorption of divalent-cations to a variety of phosphatidylcholine bilayers. Biochemistry 20:1771–1777. doi:10.1021/bi00510a010 PubMedCrossRefGoogle Scholar
  29. Nakada S, Inoue K, Nojima S, Imura N (1978) Change in permeability of liposomes caused by methylmercury and inorganic mercury. Chem Biol Interact 22:15–23. doi:10.1016/0009-2797(78)90146-1 PubMedCrossRefGoogle Scholar
  30. Passow H, Rothstein A, Clarkson TW (1961) The general pharmacology of the heavy metals. Pharmacol Rev 13:185–224PubMedGoogle Scholar
  31. Prenner E, Honsek G, Honig D, Mobius D, Lohner K (2007) Imaging of the domain organization in sphingomyelin and phosphatidylcholine monolayers. Chem Phys Lipids 145:106–118. doi:10.1016/j.chemphyslip.2006.11.002 PubMedCrossRefGoogle Scholar
  32. Rabenstein DL (1989) Metal complexes of glutathione and their biological significance. In: Dolphin D, Avramovic O, Poulson R (eds) Glutathione: chemical biochemical and medical aspects. Wiley, New York, pp 147–186Google Scholar
  33. Sarang Z, Madi A, Koy C, Varga S, Glocker MO, Ucker DS et al (2007) Tissue transglutaminase (TG2) facilitates phosphatidylserine exposure and calpain activity in calcium-induced death of erythrocytes. Cell Death Differ 14:1842–1844. doi:10.1038/sj.cdd.4402193 PubMedCrossRefGoogle Scholar
  34. Segall HJ, Wood JM (1974) Reaction of methyl mercury with plasmalogens suggests a mechanism for neurotoxicity of metal–alkyls. Nature 248:456–458. doi:10.1038/248456a0 PubMedCrossRefGoogle Scholar
  35. Shenker BJ, Rooney C, Vitale L, Shapiro IM (1992) Immunotoxic effects of mercuric compounds on human-lymphocytes and monocytes. 1. Suppression of T-cell activation. Immunopharmacol Immunotoxicol 14:539–553. doi:10.3109/08923979209005410 PubMedCrossRefGoogle Scholar
  36. Shingles R, Wimmers LE, McCarty RE (2004) Copper transport across pea thylakoid membranes. Plant Physiol 135:145–151. doi:10.1104/pp.103.037895 PubMedCrossRefGoogle Scholar
  37. Suwalski M, Ungerer B, Quevedo B, Aguilar L, Sotomayor F (1998) Cu2+ ions interact with cell membranes. J Inorg Biochem 70:233–238. doi:10.1016/S0162-0134(98)10021-1 CrossRefGoogle Scholar
  38. Suwalsky M, Ungerer B, Villena F, Cuevas F, Sotomayor CP (2000) HgCl2 disrupts the structure of the human erythrocyte membrane and model phospholipid bilayers. J Inorg Biochem 81:267–273. doi:10.1016/S0162-0134(00)00105-7 PubMedCrossRefGoogle Scholar
  39. Suwalsky M, Villena F, Norris B, Cuevas F, Sotomayor CP (2004) Cadmium-induced changes in the membrane of human erythrocytes and molecular models. J Inorg Biochem 98:1061–1066. doi:10.1016/j.jinorgbio.2004.02.027 PubMedCrossRefGoogle Scholar
  40. Vandijck PWM, Dekruijff B, Verkleij AJ, Vandeenen LLM, Degier J (1978) Comparative studies on effects of pH and Ca2+ on bilayers of various negatively charged phospholipids and their mixtures with phosphatidylcholine. Biochim Biophys Acta 512:84–96. doi:10.1016/0005-2736(78)90219-5 CrossRefGoogle Scholar
  41. Vansteveninck J, Weed RI, Rothstein A (1965) Localization of erythrocyte membrane sulfhydryl groups essential for glucose transport. J Gen Physiol 48:617–632. doi:10.1085/jgp.48.4.617 PubMedCrossRefGoogle Scholar
  42. Virtanen JK, Rissanen TH, Voutilainen S, Tuomainen TP (2007) Mercury as a risk factor for cardiovascular diseases. J Nutr Biochem 18:75–85. doi:10.1016/j.jnutbio.2006.05.001 PubMedCrossRefGoogle Scholar
  43. Watjen W, Haase H, Biagioli M, Beyersmann D (2002) Induction of apoptosis in mammalian cells by cadmium and zinc. Environ Health Perspect 110:865–867PubMedGoogle Scholar
  44. Zachowski A (1993) Phospholipids in animal eukaryotic membranes—transverse asymmetry and movement. Biochem J 294:1–14PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Mary Trang Le
    • 1
  • Jürgen Gailer
    • 2
  • Elmar J. Prenner
    • 1
  1. 1.Department of Biological SciencesUniversity of CalgaryCalgaryCanada
  2. 2.Department of Chemistry and Environmental Science ProgramUniversity of CalgaryCalgaryCanada

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