Production of immunoreactive thyroglobulin C-terminal fragments during thyroid hormone synthesis.
Here, we studied the fragmentation of the prothyroid hormone, thyroglobulin (Tg), which occurs during thyroid hormone synthesis, a process which involves iodide, thyroperoxidase, and the H2O2-generating system, consisting of glucose and glucose oxidase. Various peptides were found to be immunoreactive to autoantibodies to Tg from patients and monoclonal antibodies directed against the immunodominant region of Tg. The smallest peptide (40 kDa) bore thyroid hormones and was identified at the C-terminal end of the Tg molecule, which shows homologies with acetylcholinesterase. Similar peptides were obtained by performing metal-mediated oxidation of Tg via a Fenton reaction. It was concluded that the oxidative stress induced during hormone synthesis generates free radicals, which, in turn, cleave Tg into immunoreactive peptides.
Duthoit
C
C
Unit 38 of the French Institute of Health and Medical Research, Faculté de Médecine Timone, Université de la Méditerranée, Marseille.
Estienne
V
V
Delom
F
F
Durand-Gorde
J M
JM
Mallet
B
B
Carayon
P
P
Ruf
J
J
D000595:Amino Acid Sequence / Q000235:genetics; D018604:Epitope Mapping; D006801:Humans; D007158:Immunologic Techniques; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013954:Thyroglobulin / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D013963:Thyroid Hormones / Q000096:biosynthesis*; D014018:Tissue Distribution
D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D013963:Thyroid Hormones; D013954:Thyroglobulin