Advertisement

Biological Trace Element Research

, Volume 108, Issue 1–3, pp 225–243 | Cite as

Metal tissue kinetics in regenerating liver, thymus, spleen, and submandibular gland after partial hepatectomy in mice

  • Čedomila Milin
  • Marin Tota
  • Robert Domitrović
  • Jasminka Giacometti
  • Radojka Pantovic
  • Mira Ćuk
  • Ines Mrakovčić-Šutić
  • Hrvoje Jakovac
  • Biserka Radošević-Stašić
Original Articles

Abstract

Liver regeneration after partial hepatectomy (pHx) is a well-defined process, which involves the concerted action of extra- and intracellular factors resulting in induction of cell replication and its inhibition at the time when the entire liver mass is restored. Concomitantly, the breakdown of previously maintained tolerance and the exposure of self-antigens lead to the activation of preimmune and immune repertoires, which participate in surveillance against aberrant cells and the re-establishment of previous morphostasis. Because, in these events, important biological function might have tissue minerals that are affecting the structural integrity and enzyme activities, transduction signals, transcription and replication factors during cell proliferation and apoptosis, as well as the development and maintenance of immune functions and cytokine production, in this study we analyzed tissue dynamics of zinc, ioron magnesium, and calcium in the liver, thymus, spleen, and submandibular gland in intact and pHx mice on the 1st, 2nd, 7th, and 15th d after one-third pHx, using microwave digestion and inductivity coupled plasma spectrometry. The data showed that pHx induces significant and interconnected changes in all of the estimated metals not only in the regenerating liver but also in the lymphatic tissues and submandibular gland, indicating their importance for the control of growth processes.

Index Entries

Zinc iron calcium magnesuim ICP spectroscopy atomic absorption partial hepatectomy liver regeneration thymus spleen submandibular gland 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    N. Fausto, A. D. Laird, and E. M. Webber, Liver regeneration. 2. Role of growth factors and cytokines in hepatic regeneration, FASEB J. 9, 1527–1536 (1995).PubMedGoogle Scholar
  2. 2.
    G. K. Michalopoulos and M. C. DeFrances, Liver regeneration, Science 276, 60–66 (1997).PubMedCrossRefGoogle Scholar
  3. 3.
    N. Fausto, Liver regeneration and repair: hepatocytes, progenitor cells, and stem cells, Hepatology 39, 477–487 (2004).CrossRefGoogle Scholar
  4. 4.
    R. Traub, Liver regeneration: from myth to mechanism, Nature Rev. 5, 836–847 (2004).CrossRefGoogle Scholar
  5. 5.
    E. M. Webber, J. Bruix, R. H. Pierce, et al., Tumor necrosis factor primes hepatocytes for DNA replication in the rat, Hepatology 28, 1226–1234 (1998).PubMedCrossRefGoogle Scholar
  6. 6.
    A. M. Diehl and R. M. Rai, Liver regeneration 3: Regulation of signal transduction during liver regeneration, FASEB J. 10, 215–227 (1996).PubMedGoogle Scholar
  7. 7.
    B. A. Haber, K. L. Mohn, R. H. Diamond, et al., Induction patterns of 70 genes during nine days after hepatectomy define the temporal course of liver regeneration, J. Clin. Invest. 9, 1319–1326 (1993).CrossRefGoogle Scholar
  8. 8.
    J. H. Albrecht and L. K. Hansen, Cyclin D1 promotes mitogen-independent cell cycle progression in hepatocytes, Cell Growth Differ. 10, 397–404 (1999).PubMedGoogle Scholar
  9. 9.
    D. B. Stolz, W. M. Mars, B. E. Petersen, et al., Growth factor signal transduction immediately after two-thirds partial hepatectomy in the rat, Cancer Res. 59, 4954–4960 (1999).Google Scholar
  10. 10.
    P. Skov Olsen, S. Boesby, P. Kirkegaard, et al., Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats, Hepatology 8, 992–996 (1988).PubMedCrossRefGoogle Scholar
  11. 11.
    S. Noguchi, Y. Ohba, and T. Oka, Influence of epidermal growth factor on liver regeneration after partial hepatectomy in mice, J. Endocrinol. 128, 425–431 (1991).PubMedCrossRefGoogle Scholar
  12. 12.
    M. Jo, D. B. Stolz, J. E. Esplen, et al., Cross-talk between epidermal growth factor receptor and c-Met signal pathways in transformed cells, J. Biol. Chem. 275, 8806–8811 (2000).PubMedCrossRefGoogle Scholar
  13. 13.
    J. L. Cruise, S. J. Knechtle, R. R. Bollinger, et al., Alpha 1-adrenergic effects and liver regeneration, Hepatology 7, 1189–1194 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    P. Matzinger, The danger model: a renewed sense of self, Science 296, 301–305 (2002).PubMedCrossRefGoogle Scholar
  15. 15.
    T. Abo, T. Kawamura, and H. Watanabe, Physiological responses of extrathymic T cells in the liver, Immunol. Rev. 174, 135–149 (2000).PubMedCrossRefGoogle Scholar
  16. 16.
    T. Kato, Y. Sato, S. Takalashi, et al., Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy, J. Hepatol. 40, 285–290 (2004).PubMedCrossRefGoogle Scholar
  17. 17.
    T. Naito, T. Kawamura, M. Bannai, et al., Simultaneous activation of natural killer T cells and autoantibody production in mice injected with denatured syngeneic liver tissue, Clin. Exp. Immunol. 129, 397–404 (2002).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Bendelac, Mouse NK1+T cells, Curr. Opln. Immunol. 7, 367–374 (1995).CrossRefGoogle Scholar
  19. 19.
    D. I. Godfrey, H. R. MacDonald, M. Kronenberg, et al., NKT cells: what's in a name? Nat. Rev. Immunol. 4, 231–237 (2004).PubMedCrossRefGoogle Scholar
  20. 20.
    B. Radosevic-Stasic, Z. Trobonjaca, J. Ravlic-Gulan, et al., On the role of natural killer cells in liver regeneration, Period. Biol. 100, 429–434 (1998).Google Scholar
  21. 21.
    I. Mrakovcic-Sutic, M. Simin, D. Radic, et al., Syngeneic pregnancy induces overex-pression of natural killer T cells in matermal liver, Scand. J. Immunol. 58, 358–366 (2003).PubMedCrossRefGoogle Scholar
  22. 22.
    I. Mrakovcic-Sutic, B. Radosevic-Stasic, M. Simin, et al., Augmentation of NKT and NK cell-mediated cytotoxicity by peptidoglycan monomer linked with zinc, Mediators Inflamm. 11, 129–135 (2002).PubMedCrossRefGoogle Scholar
  23. 23.
    J. F. Bach Autoimmume diseases as the loss of active “self-control”, Ann. NY Acad. Sci. 998, 161–177 (2003).PubMedCrossRefGoogle Scholar
  24. 24.
    H. Tapiero and K. D. Tew, Trace elements in human physiology and pathology: zinc and metallothioneins, Biomed. Pharmacother. 57, 399–411 (2003).PubMedCrossRefGoogle Scholar
  25. 25.
    A. S. Prasad, Zinc deficiency: its characterization and treatment, Metal Ions Biol. Syst. 41, 103–137 (2004).Google Scholar
  26. 26.
    P. J. Fraker and L. E. King, Reprogramming of the immune system during zinc deficiency, Annu. Rev. Nutr. 24, 277–298 (2004).PubMedCrossRefGoogle Scholar
  27. 27.
    L. Rink and P. Gabriel, Zinc and the immune system, Proc. Nutr. Soc. 59, 541–552 (2000).PubMedCrossRefGoogle Scholar
  28. 28.
    E. Mocchegiani, R. Giacconi, E. Muti, et al., Zinc, immune plasticity, aging, and successful aging: role of metallothionein, Ann. NY Acad. Sci. 1019, 127–134 (2004).PubMedCrossRefGoogle Scholar
  29. 29.
    M. D. Lastra, R. Pastelin, A. Camacho, et al., Zinc intervention on macrophages and lymphocytes response, J. Trace Elements Med. Biol. 15, 5–10 (2001).CrossRefGoogle Scholar
  30. 30.
    T. Dudev and C. Lim, Principles governing Mg, Ca, and Zn binding and selectivity in proteins, Chem. Rev. 103, 773–788 (2003).PubMedCrossRefGoogle Scholar
  31. 31.
    M. P. Vaquero, Magnesium and trace elements in the elderly: intake, status and recommendations, J. Nutr. Health Aging 6, 147–153 (2002).PubMedGoogle Scholar
  32. 32.
    P. Evans and B. Halliwell, Micronutrients: oxidant/antioxidant status, Br. J. Nutr. 85(Suppl. 2), S67-S74 (2001).PubMedCrossRefGoogle Scholar
  33. 33.
    D. Verbanac, C. Milin, R. Domitrovic, et al., Determination of standard zinc values in the intact tissues of mice by ICP spectrometry, Biol. Trace Element Res. 57, 91–96 (1997).Google Scholar
  34. 34.
    C. Milin, B. Radosevic-Stasic, D. Verbanac, et al., Changes of hepatic and thymic zinc during the liver regeneration in hepatectomized mice, Croatica Chem. Acta 68, 559–567 (1995).Google Scholar
  35. 35.
    E. Mocchegiani, D. Verbanac, L. Santarelli, et al., Zinc and metallothioneins on cellular immune effectiveness during liver regeneration in young and old mice, Life Sci. 61, 1125–1145 (1997).PubMedCrossRefGoogle Scholar
  36. 36.
    C. Cipriano, R. Giacconi, M. Muzzioli, et al., Metallothionein (I+II) confers, via c-myc, immune plasticity in oldest mice: model of partial hepatectomy/liver regeneration, Mech. Ageing. Dev. 124, 877–886 (2003).PubMedCrossRefGoogle Scholar
  37. 37.
    K. Tsujikawa, N. Suzuki, K. Sagawa, et al., Induction and subcellular localization of metallothionein in regenerating rat liver, Eur. J. Cell. Biol. 63, 240–246 (1994).PubMedGoogle Scholar
  38. 38.
    M. G. Cherian, Nuclear and cytoplasmic localization of metallothionein in human liver during development and in tumor cells, in Metallothionein III (K. T. Suzuki, N. Imura, and M. Kimura, eds.), Birkhaüser-Verlag, Basel, pp. 175–187 (1993).Google Scholar
  39. 39.
    M. Sato, M. Sasaki, and H. Hojo, Induction of metallothionein synthesis by oxidative stress and possible role in acute phase response, in Metallothionein III (K. T. Suzuki, N. Imura, and M. Kimura, eds.), Birkhaüser-Verlag, Basel, pp. 125–140 (1993).Google Scholar
  40. 40.
    W. Maret and B. L. Vallee, Thiolate ligands in metallothionein confer redox activity on zinc clusters, Proc. Natl. Acad. sci. USA 95, 3478–3482 (1998).PubMedCrossRefGoogle Scholar
  41. 41.
    C. M. St Croix, K. J. Wasserloos, K. E. Dineley, et al., Nitric oxide-induced changes in intracellular zinc homeostasis are mediated by metallothionein/thionein, Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L185-L192 (2002).PubMedGoogle Scholar
  42. 42.
    W. Maret, C. Jacob, B. L. Vallee, et al., Inhibitory sites in enzymes: zinc removal and reactivation by thionein, Proc. Natl. Acad. Sci. USA 96, 1936–1940 (1999).PubMedCrossRefGoogle Scholar
  43. 43.
    J. Zeng, R. Heuchel, W. Schaffner, et al., Thionein (apometallothionein) can modulate DNA binding and transcription activation by zinc finger containing factor Sp1, FEBS Lett. 279, 310–312 (1991).PubMedCrossRefGoogle Scholar
  44. 44.
    C. Kerkhoff, T. Vogl, W. Nacken, et al., Zinc binding reverses the calcium-induced arachidonic acid-binding capacity of the S100A8/A9 protein complex, FEBS Lett. 46, 134–138 (1999).CrossRefGoogle Scholar
  45. 45.
    W. Nacken, J. Roth, C. Sorg, et al., S100A9/S100A8: myeloid representatives of the S100 protein family as prominent players in innate immunity, Microsc. Res. Tech. 60, 569–580 (2003).PubMedCrossRefGoogle Scholar
  46. 46.
    R. Shimoda, W. E. Achanzar, W. Qu, et al., Metallothionein is a potential negative regulator of apoptosis, Toxicol. Sci. 73, 294–300 (2003).PubMedCrossRefGoogle Scholar
  47. 47.
    Y. Fukamachi, Y. Karasaki, T. Sugiura, et al., Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an increase of the Bcl-2/Bax ratio, Biochem. Biophys. Res. Commun. 246, 364–369 (1998).PubMedCrossRefGoogle Scholar
  48. 48.
    C. Giannakis, I. J. Forbes, and P. D. Zalewski, Ca2+/Mg(2+)-dependent nuclease: tissue distribution, relationship to inter-nucleosomal DNA fragmentation and inhibition by Zn2+, Biochem. Biophys. Res. Commun. 181, 915–920 (1991).PubMedCrossRefGoogle Scholar
  49. 49.
    P. Schneider, N. Holler, J. L. Bodmer, et al., Conversion of membrane-bound Fas (CD95) ligand to its soluble form is associated with downregulation of its proapoptotic activity and loss of liver toxicity, J. Exp. Med. 187, 1205–1213 (1998).PubMedCrossRefGoogle Scholar
  50. 50.
    E. Mocchegiani, M. Muzzioli, and R. Giacconi, Zinc, metallothioneins, immune responses, survival and ageing, Biogerontology 1, 133–143 (2000).PubMedCrossRefGoogle Scholar
  51. 51.
    E. Mocchegiani, R. Giacconi, C. Cipriano, et al., MtmRNA gene expression, via IL-6 and glucocorticoids, as potential genetic marker of immunosenescence: lessons from very old mice and humans, Exp. Gerontol. 37, 349–357 (2002).PubMedCrossRefGoogle Scholar
  52. 52.
    A. Molotkov, N. Nishimura, M. Satoh, et al., Role of IL-6 in the induction of hepatic metallothionein in mice after partial hepatectomy, Life Sci. 66, 963–970 (2000).PubMedCrossRefGoogle Scholar
  53. 53.
    H. Bruunsgaard, M. Pedersen, and B. K. Pedersen, Aging and proinflammatory cytokines, Curr. Opin. Hematol. 8, 131–136 (2001).PubMedCrossRefGoogle Scholar
  54. 54.
    E. Mocchegiani, M. Muzzioli, R. Giacconi, et al., Metallothioneins/PARP-1/II-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply, Mech. Ageing Dev. 124, 459–468 (2003).PubMedCrossRefGoogle Scholar
  55. 55.
    C. O. Simpkins, Metallothionein in human disease, Cell. Mol. Biol. (Noisy-le-Grand) 46, 465–488 (2000).Google Scholar
  56. 56.
    P. J. Fraker, L. E. King, T. Laakko, et al., The dynamic link between the integrity of the immune system and zinc status, J. Nutr. 130, 1399S-1406S (2000).PubMedGoogle Scholar
  57. 57.
    L. E. King, F. Osati-Ashtiani, and P. J. Fraker, Apoptosis plays a distinct role in the loss of precursor lymphocytes during zinc deficiency in mice, J. Nutr. 132, 974–979 (2002).PubMedGoogle Scholar
  58. 58.
    J. F. Bach and M. Dardenne, Thymulin, a zinc-dependent hormone, Med. Oncol. Tumor Pharmacother 6, 25–29 (1989).PubMedGoogle Scholar
  59. 59.
    F. Di Virgilio, P. Chiozzi, D. Ferrari, et al., Nucleotide receptors: an emerging family of regulatory molecules in blood cells, Blood 97, 587–600 (2001).PubMedCrossRefGoogle Scholar
  60. 60.
    R. S. Lewis, Calcium oscillations in T-cells: mechanisms and consequences for gene expression, Biochem. Soc. Trans. 31, 925–929 (2003).PubMedGoogle Scholar
  61. 61.
    G. Panyi, Z. Varga, and R. Gaspar, Ion channels and lymphocyte activation, Immunol. Lett. 92, 55–66 (2004).PubMedCrossRefGoogle Scholar
  62. 62.
    L. L. Chen, A. Whitty, D. Scott, et al., Evidence that ligand and metal ion binding to integrin alpha 4beta 1 are regulated through a coupled equilbrium, J. Biol. Chem. 276, 36,520–36,529 (2001).Google Scholar
  63. 63.
    R. Mathison, J. S. Davison, and A. D. Betus, Neuroendocrine regulation of intlammation and tissue repair by submandibular gland factors, Immunol. Today. 15, 527–532 (1994).PubMedCrossRefGoogle Scholar
  64. 64.
    E. Sabbadini and I. Berczi, The submandibular gland: a key organ in the neuroimmuno-regulatory network?, Neuroimmunomodulation 2, 184–202 (1995).PubMedCrossRefGoogle Scholar
  65. 65.
    C. Rougeot, I. Rosinski-Chupin, R. Mathison, et al., Rodent submandibular gland peptide hormones and other biologically active peptides, Peptides 21, 443–455 (2000).PubMedCrossRefGoogle Scholar
  66. 66.
    T. J. Bartness, C. K. Song, and G. E. Demas, SCN efferents to peripheral tissues: implications for biological rhythms, J. Biol. Rhythms 16, 196–204 (2001).PubMedCrossRefGoogle Scholar
  67. 67.
    S. Ruff-Jamison, Z. Zhong, Z. Wen, et al., Epidermal growth factor and lipopolysaccharide activate Stat3 transcription factor in mouse liver, J. Biol. Chem. 269, 21,933–21,935 (1994).Google Scholar
  68. 68.
    R. Giacconi, C. Cipriano, M. Muzzioli, et al., Interrelationships among brain, endocrine and immune response in ageing and successful ageing: role of metallothionein III isoform, Mech. Ageing Dev. 124, 371–378 (2003).PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Čedomila Milin
    • 1
  • Marin Tota
    • 1
  • Robert Domitrović
    • 1
  • Jasminka Giacometti
    • 1
  • Radojka Pantovic
    • 1
  • Mira Ćuk
    • 2
  • Ines Mrakovčić-Šutić
    • 2
  • Hrvoje Jakovac
    • 2
  • Biserka Radošević-Stašić
    • 2
  1. 1.Department of Chemistry and BiochemistryMedical Faculty of RijekaRijekaCroatia
  2. 2.Department of Physiology and ImmunologyMedical Faculty of RijekaRijekaCroatia

Personalised recommendations