Role of peroxidase inhibition by insulin in the bovine thyroid cell proliferation mechanism.
Monolayer primary cultures of thyroid cells produce, in the presence of insulin, a cytosolic inhibitor of thyroid peroxidase (TPO), lacto peroxidase (LPO), horseradish peroxidase (HRPO) and glutathione peroxidase (GPX). The inhibitor, localized in the cytosol, is thermostable and hydrophylic. Its molecular mass is less than 2 kDa. The inhibitory activity, resistant to proteolytic and nucleolytic enzymes, disappears with sodium metaperiodate treatment, as an oxidant of carbohydrates, supporting its oligosaccharide structure. The presence of inositol, mannose, glucose, the specific inhibition of cyclic AMP-dependent protein kinase and the disappearance of peroxidase inhibition by alkaline phosphatase and alpha-mannosidase in purified samples confirms its chemical structure as inositol phosphoglycan-like. Purification by anionic interchange shows that the peroxidase inhibitor elutes like the two subtypes of inositol phosphoglycans (IPG)P and A, characterized as signal transducers of insulin action. Insulin significantly increases the concentration of the peroxidase inhibitor in a thyroid cell culture at 48 h. The addition of both isolated substances to a primary thyroid culture produces, after 30 min, a significant increase in hydrogen peroxide (H2O2) concentration in the medium, concomitantly with the disappearance of the GPX activity in the same conditions. The presence of insulin or anyone of both products, during 48 h, induces cell proliferation of the thyroid cell culture. In conclusion, insulin stimulates thyroid cell division through the effect of a peroxidase inhibitor, as its second messenger. The inhibition of GPX by its action positively modulates the H2O2 level, which would produce, as was demonstrated by other authors, the signal for cell proliferation.
Krawiec
León
L
Argentine National Research Council (CONICET), Buenos Aires, Argentina. krawiec@cnea.gov.ar
Pizarro
Ramón A
RA
Aphalo
Paula
P
de Cavanagh
Elena M V
EM
Pisarev
Mario A
MA
Juvenal
Guillermo J
GJ
Policastro
Lucía
L
Bocanera
Laura V
LV
D000818:Animals; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D007328:Insulin / Q000494:pharmacology*; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D007328:Insulin; D010544:Peroxidases