Ukr.Biochem.J. 2014; Volume 86, Issue 3, May-Jun, pp. 107-113

doi: http://dx.doi.org/10.15407/ubj86.03.107

Trace elements storage peculiarities and metallothionein content in human thyroid gland under iodine deficiency euthyroid nodular goiter

H. I. Falfushynska1,2, L. L. Gnatyshyna1, O. Osadchuk2, V. O. Shidlovski2, О. B. Stoliar1

1Ternopil Volodymyr Hnatiuk National Pedagogical University, Ukraine;
2I.Ya. Horbachevski Ternopil State Medical University, Ukraine;
e-mail: halynka.f@gmail.com

Accumulation of iodine and copper in the node, paranodular and contralateral (not affected tissue by node) tissues of thyroid gland in relation to the level of metal-binding proteins, potential antioxidants and oxidative changes in tissue was investigated. To assess the severity of the pathological process the molecular markers of cytotoxicity were used. The reduction of total iodine (by 19.5%), increase of inorganic iodine fraction (by 82.4%) and total copper content (twice) in paranodular and nodular tissues compared with contrlateral part have been established. Excess of copper in goitrous-changes tissue was partially accumulated in the metallothioneins. The level of metal-binding form of metallothioneins and reserve of free thiols of these proteins was higher two-three times and lower content of reduced glutathione in node-affected tissue compared to the contralateral part. Signs of cytotoxicity among them: higher cathepsine D free activity (up to 84.6% and 134.4% in paranodular tissue and node respectively) and higher level of DNA strand breaks in the node (up to 22.6%) were observed. In paranodular tissue the range of indices variability compared with parenchyma of contralateral part is shorter than in the node. Thus, under low level of iodine organification and high copper level in goitrous-modified tissue of thyroid gland metallothionein may provide a partial compensatory effect on prooxidative processes.

Keywords: , , , , , ,


References:

  1. Maier J, van Steeg H, van Oostrom C, Paschke R, Weiss RE, Krohn K. Iodine deficiency activates antioxidant genes and causes DNA damage in the thyroid gland of rats and mice. Biochim Biophys Acta. 2007 Jun;1773(6):990-9. PubMed, CrossRef
  2. Erdamar H, Cimen B, Gülcemal H, Saraymen R, Yerer B, Demirci H. Increased lipid peroxidation and impaired enzymatic antioxidant defense mechanism in thyroid tissue with multinodular goiter and papillary carcinoma. Clin Biochem. 2010 May;43(7-8):650-4. PubMed, CrossRef
  3. Polyanskyi I., Sheremet M., Chamray G. Activity of the peroxidation processes and state of the antioxidant system of patients with nodular euthyroid goiter, and possibility of curing. Clin Endocrin Endocrine Surgery. 2003;(3(4)):34-38.
  4. Falfushynska H. I., Gnatyshyna L. L., Osadchuk D. V., Shidlovski V. O., Stoliar О. B. Metal-binding functions and antioxidant properties in human thyroid gland under iodine deficient nodular colloidal goiter. Ukr Biokhim Zhurn. 2011 Nov-Dec;83(6):92-7.  PubMed
  5. Freake HC, Govoni KE, Guda K, Huang C, Zinn SA. Actions and interactions of thyroid hormone and zinc status in growing rats. J Nutr. 2001 Apr;131(4):1135-41. PubMed
  6. Biggs TW, D’Anna H. Rapid increase in copper concentrations in a new marina, San Diego Bay. Mar Pollut Bull. 2012 Mar;64(3):627-35.  PubMed, CrossRef
  7. Ethical aspects in the prevention of iodine-related diseases: round table discussions.  III National Congress on bioethics. Kyiv, 2007.
  8. Stolyar OB, Loumbourdis NS, Falfushinska HI, Romanchuk LD. Comparison of metal bioavailability in frogs from urban and rural sites of Western Ukraine. Arch Environ Contam Toxicol. 2008 Jan;54(1):107-13. PubMed, CrossRef
  9. Bozhkov AI. Three dose-dependent stages of the effect of copper ions on functional activity of biological systems. Biochemistry (Mosc). 1997 Feb;62(2):149-57. PubMed
  10. Maret W. Redox biochemistry of mammalian metallothioneins. J Biol Inorg Chem. 2011 Oct;16(7):1079-86. Review. PubMed, CrossRef
  11. Ferrario C, Lavagni P, Gariboldi M, Miranda C, Losa M, Cleris L, Formelli F, Pilotti S, Pierotti MA, Greco A. Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma. Lab Invest. 2008 May;88(5):474-81. PubMedCrossRef
  12. Falfushynska HI, Gnatyshyna LL, Stoliar OB. Population-related molecular responses on the effect of pesticides in Carassius auratus gibelio. Comp Biochem Physiol C Toxicol Pharmacol. 2012 Mar;155(2):396-406. PubMedCrossRef
  13. Viarengo A, Ponzano E, Dondero F, Fabbri R. A simple spectrophotometric method for metallothionein evaluation in marine organisms: an application to Mediterranean and Antarctic molluscs. Mar Environ Res. 1997;44(1):69–84.  CrossRef
  14. Nielson KB, Winge DR. Independence of the domains of metallothionein in metal binding. J Biol Chem. 1985 Jul 25;260(15):8698-701.  PubMed
  15. Anderson ME. Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol. 1985;113:548-55. PubMed, CrossRef
  16. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974 Nov 25;249(22):7130-9. PubMed
  17. Viarengo A, Burlando B, Cavaletto M, Marchi B, Ponzano E, Blasco J. Role of metallothionein against oxidative stress in the mussel Mytilus galloprovincialis. Am J Physiol. 1999 Dec;277(6 Pt 2):R1612-9. PubMed
  18. Olive PL. DNA precipitation assay: a rapid and simple method for detecting DNA damage in mammalian cells. Environ Mol Mutagen. 1988;11(4):487–495. PubMed, CrossRef
  19. Dingle JT, Barrett AJ, Weston PD. Cathepsin D. Characteristics of immunoinhibition and the confirmation of a role in cartilage breakdown. Biochem J. 1971 Jun;123(1):1-13. PubMed, PubMedCentral
  20. Pat. 45298 UA IPC 2009. The method of integral assessment of the biological response to the state of the aquatic environment / Stolyar O. B., Falfushynska H. I., Mishchuk O. V. – Publ. 10.11.2009, Bul. N 21.
  21. Shidlovskyi O.V., Osadchuk D.V.,  Falfushynska H.I. Intrathyroid iodine in patients w ith unilateral nodular colloid endemic goiter. Endokrynologia. 2013;18(3):11–15.
  22. Stoliar O. B., Lushchak V. I. Oxidative Stress – Environmental Induction And Dietary Antioxidants. Ed. Dr. Volodymyr Lushchak.  InTech, 2012.  P. 131–166.
  23. Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 2012 Dec;45(6):487-98. Review. PubMed, CrossRef
  24. Dunn AD, Crutchfield HE, Dunn JT. Thyroglobulin processing by thyroidal proteases. Major sites of cleavage by cathepsins B, D, and L. J Biol Chem. 1991 Oct 25;266(30):20198-204. PubMed
  25. Tsukuba T, Okamoto K, Yasuda Y, Morikawa W, Nakanishi H, Yamamoto K. New functional aspects of cathepsin D and cathepsin E. Mol Cells. 2000 Dec 31;10(6):601-11. Review. PubMed, CrossRef
  26. Marchi B, Burlando B, Moore MN, Viarengo A. Mercury- and copper-induced lysosomal membrane destabilisation depends on [Ca2+]i dependent phospholipase A2 activation. Aquat Toxicol. 2004 Feb 10;66(2):197-204. PubMed, CrossRef
  27. Persson HL. Iron-dependent lysosomal destabilization initiates silica-induced apoptosis in murine macrophages. Toxicol Lett. 2005 Nov 15;159(2):124-33. PubMed, CrossRef
  28. Hidalgo J, Garvey JS, Armario A. On the metallothionein, glutathione and cysteine relationship in rat liver. J Pharmacol Exp Ther. 1990 Nov;255(2):554-64. PubMed
  29. Thornalley PJ, Vasák M. Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with superoxide and hydroxyl radicals. Biochim Biophys Acta. 1985 Jan 21;827(1):36-44. PubMed, CrossRef

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