We recently reported that, during in vitro thyroid-hormone synthesis, H2O2 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 H2O2 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 H2O2 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 40kDa and entered human thyrocytes more efficiently than the entire Tg. These data suggest that thyrocytes exposed to locally increased H2O2 doses accumulate fragmented Tg for further delivery into surrounding living thyrocytes in the course of an autoimmune response.
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December 2001
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Research Article|
December 10 2001
Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity?
Christine DUTHOIT;
Christine DUTHOIT
1
∗U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France
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Valérie ESTIENNE;
Valérie ESTIENNE
∗U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France
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Annie GIRAUD;
Annie GIRAUD
∗U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France
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Josée-Martine DURAND-GORDE;
Josée-Martine DURAND-GORDE
∗U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France
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Åse Krogh RASMUSSEN;
Åse Krogh RASMUSSEN
†Medical Department PE, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Ulla FELDT-RASMUSSEN;
Ulla FELDT-RASMUSSEN
†Medical Department PE, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Pierre CARAYON;
Pierre CARAYON
∗U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France
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Jean RUF
Jean RUF
2
∗U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, Marseille, France
2To whom correspondence should be addressed (e-mail Jean.Ruf@medecine.univ-mrs.fr).
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Publisher: Portland Press Ltd
Received:
June 29 2001
Revision Received:
August 24 2001
Accepted:
October 15 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 360 (3): 557–562.
Article history
Received:
June 29 2001
Revision Received:
August 24 2001
Accepted:
October 15 2001
Citation
Christine DUTHOIT, Valérie ESTIENNE, Annie GIRAUD, Josée-Martine DURAND-GORDE, Åse Krogh RASMUSSEN, Ulla FELDT-RASMUSSEN, Pierre CARAYON, Jean RUF; Hydrogen peroxide-induced production of a 40 kDa immunoreactive thyroglobulin fragment in human thyroid cells: the onset of thyroid autoimmunity?. Biochem J 15 December 2001; 360 (3): 557–562. doi: https://doi.org/10.1042/bj3600557
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