Hydrogen Peroxide-induced Production of a 40 KDa Immunoreactive Thyroglobulin Fragment in Human Thyroid Cells: the Onset of Thyroid Autoimmunity?

Overview

Journal Biochem J

Specialty Biochemistry

Date 2001 Dec 12

PMID 11736644

Citations 20

Authors

C Duthoit

V Estienne

A Giraud

A K Rasmussen

U Feldt-Rasmussen

P Carayon

J Ruf

Affiliations

Soon will be listed here.

Abstract

We recently reported that, during in vitro thyroid-hormone synthesis, H(2)O(2) stress cleaved thyroglobulin (Tg) into C-terminal peptides. These peptides were found to contain the immunodominant region of Tg recognized by Tg autoantibodies from patients with an autoimmune thyroid disease. To test the hypothesis that Tg fragmentation is an early upstream initiating event involved in Tg autoimmune response and the consequence of oxidative injuries, we studied the effect of H(2)O(2) stress on human thyroid cells. In culture conditions allowing Tg synthesis and iodine organification by the cells, we found that bolus addition of increasing millimolar doses of H(2)O(2) induced a dose-response appearance of floating cells in the culture medium. These cells apparently resulted from a necrotic process, and they bore iodinated Tg fragments. These fragments were found to be similar to those previously obtained in vitro from purified Tg. In both cases, Tg peptides were recognized by a well-defined monoclonal antibody directed to the immunodominant region of Tg. The smallest immunoreactive Tg peptide had a molecular mass of 40 kDa and entered human thyrocytes more efficiently than the entire Tg. These data suggest that thyrocytes exposed to locally increased H(2)O(2) doses accumulate fragmented Tg for further delivery into surrounding living thyrocytes in the course of an autoimmune response.

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References

Rasmussen A, Kayser L, Perrild H, Brandt M, Bech K, Feldt-Rasmussen U . Human thyroid epithelial cells cultured in monolayers. I. Decreased thyroglobulin and cAMP response to TSH in 12-week-old secondary and tertiary cultures. Mol Cell Endocrinol. 1996; 116(2):165-72. DOI: 10.1016/0303-7207(95)03711-x. View

Kong Y, McCormick D, Wan Q, Motte R, Fuller B, Giraldo A . Primary hormonogenic sites as conserved autoepitopes on thyroglobulin in murine autoimmune thyroiditis. Secondary role of iodination. J Immunol. 1995; 155(12):5847-54. View

Gardner A, Xu F, Fady C, Jacoby F, Duffey D, Tu Y . Apoptotic vs. nonapoptotic cytotoxicity induced by hydrogen peroxide. Free Radic Biol Med. 1997; 22(1-2):73-83. DOI: 10.1016/s0891-5849(96)00235-3. View

Giraud A, Siffroi S, LANET J, Franc J . Binding and internalization of thyroglobulin: selectivity, pH dependence, and lack of tissue specificity. Endocrinology. 1997; 138(6):2325-32. DOI: 10.1210/endo.138.6.5195. View

Landry S . Local protein instability predictive of helper T-cell epitopes. Immunol Today. 1997; 18(11):527-32. DOI: 10.1016/s0167-5699(97)01152-3. View

Braley-Mullen H, Sharp G . A thyroxine-containing thyroglobulin peptide induces both lymphocytic and granulomatous forms of experimental autoimmune thyroiditis. J Autoimmun. 1998; 10(6):531-40. DOI: 10.1006/jaut.1997.0160. View

Riou C, Remy C, Rabilloud R, Rousset B, Fonlupt P . H2O2 induces apoptosis of pig thyrocytes in culture. J Endocrinol. 1998; 156(2):315-22. DOI: 10.1677/joe.0.1560315. View

Catalfamo M, Serradell L, Kolkowski E, Sospedra M, Vives-Pi M, Pujol-Borrell R . HLA-DM and invariant chain are expressed by thyroid follicular cells, enabling the expression of compact DR molecules. Int Immunol. 1999; 11(2):269-77. DOI: 10.1093/intimm/11.2.269. View

Wu Z, Biro P, Mirakian R, Hammond L, Curcio F, Ambesi-Impiombato F . HLA-DMB expression by thyrocytes: indication of the antigen-processing and possible presenting capability of thyroid cells. Clin Exp Immunol. 1999; 116(1):62-9. PMC: 1905228. DOI: 10.1046/j.1365-2249.1999.00831.x. View

10.

Riou C, Tonoli H, Rabilloud R, Fonlupt P, Rousset B . Susceptibility of differentiated thyrocytes in primary culture to undergo apoptosis after exposure to hydrogen peroxide: relation with the level of expression of apoptosis regulatory proteins, Bcl-2 and Bax. Endocrinology. 1999; 140(5):1990-7. DOI: 10.1210/endo.140.5.6725. View

11.

Marino M, Friedlander J, McCluskey R, Andrews D . Identification of a heparin-binding region of rat thyroglobulin involved in megalin binding. J Biol Chem. 1999; 274(43):30377-86. DOI: 10.1074/jbc.274.43.30377. View

12.

Dupuy C, Ohayon R, Valent A, Noel-Hudson M, Deme D, Virion A . Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas. J Biol Chem. 1999; 274(52):37265-9. DOI: 10.1074/jbc.274.52.37265. View

13.

Antunes F, Cadenas E . Estimation of H2O2 gradients across biomembranes. FEBS Lett. 2000; 475(2):121-6. DOI: 10.1016/s0014-5793(00)01638-0. View

14.

Duthoit C, Estienne V, Delom F, Mallet B, Carayon P, Ruf J . Production of immunoreactive thyroglobulin C-terminal fragments during thyroid hormone synthesis. Endocrinology. 2000; 141(7):2518-25. DOI: 10.1210/endo.141.7.7573. View

15.

Marino M, McCluskey R . Megalin-mediated transcytosis of thyroglobulin by thyroid cells is a calmodulin-dependent process. Thyroid. 2000; 10(6):461-9. View

16.

Palazzo F, Hammond L, Goode A, Mirakian R . Death of the autoimmune thyrocyte: is it pushed or does it jump?. Thyroid. 2000; 10(7):561-72. DOI: 10.1089/thy.2000.10.561. View

17.

Komosinska-Vassev K, Olczyk K, Kucharz E, Marcisz C, Winsz-Szczotka K, Kotulska A . Free radical activity and antioxidant defense mechanisms in patients with hyperthyroidism due to Graves' disease during therapy. Clin Chim Acta. 2000; 300(1-2):107-17. DOI: 10.1016/s0009-8981(00)00306-5. View

18.

Antunes F, Cadenas E . Cellular titration of apoptosis with steady state concentrations of H(2)O(2): submicromolar levels of H(2)O(2) induce apoptosis through Fenton chemistry independent of the cellular thiol state. Free Radic Biol Med. 2001; 30(9):1008-18. DOI: 10.1016/s0891-5849(01)00493-2. View

19.

Antunes F, Cadenas E, Brunk U . Apoptosis induced by exposure to a low steady-state concentration of H2O2 is a consequence of lysosomal rupture. Biochem J. 2001; 356(Pt 2):549-55. PMC: 1221868. DOI: 10.1042/0264-6021:3560549. View

20.

Delom F, Nlend M, LANET J, Franc J, Giraud A . Identification of thyroglobulin domain(s) involved in cell-surface binding and endocytosis. J Endocrinol. 2001; 170(1):217-26. DOI: 10.1677/joe.0.1700217. View