Cathepsin C and plasma glutamate carboxypeptidase secreted from Fischer rat thyroid cells liberate thyroxin from the N-terminus of thyroglobulin

The release of a thyroid hormone from thyroglobulin is controlled by a complex regulatory system. We focused on the extracellular action of two lysosomal enzymes, cathepsin C (catC, dipeptidyl peptidase I) and PGCP (lysosomal dipeptidase), on thyroglobulin, and their ability to liberate the hormone...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Biochimie 2012-03, Vol.94 (3), p.719-726
Hauptverfasser: Suban, Dejan, Zajc, Tajana, Renko, Miha, Turk, Boris, Turk, Vito, Dolenc, Iztok
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The release of a thyroid hormone from thyroglobulin is controlled by a complex regulatory system. We focused on the extracellular action of two lysosomal enzymes, cathepsin C (catC, dipeptidyl peptidase I) and PGCP (lysosomal dipeptidase), on thyroglobulin, and their ability to liberate the hormone thyroxin. Cathepsin C, an exopeptidase, removes dipeptides from the N-terminus of substrates, and PGCP hydrolyses dipeptides to amino acids. In vitro experiments proved that cathepsin C removes up to 12 amino acids from the N-terminus of porcine thyroglobulin, including a dipeptide with thyroxin on position 5. The newly formed N-terminus, Arg-Pro-, was not hydrolysed further by cathepsin C. Cell culture experiments with FRTL-5 cell line showed localization of cathepsin C and PGCP and their secretion into the medium. Secretion of the active cathepsin C from FRTL-5 cells is stimulated by TSH, insulin, and/or somatostatin. The released enzymes liberate thyroxin from porcine thyroglobulin added to media. The hormone liberation can be reduced by synthetic inhibitors of cysteine proteinases and metalloproteinases. Additionally, we show that TSH, insulin, and/or somatostatin induce up-regulation of N-acetylglucosaminyltransferase 1, the enzyme responsible for the initiation of biosynthesis of hybrid and complex N-glycosylation of proteins. ► Extracellular cathepsin C and PGCP liberate thyroxin from thyroglobulin. ► Cathepsin C removes up to 12 amino acids from the N-terminal part of thyroglobulin. ► Cathepsin C and PGCP are secreted from FRTL-5 cells. ► The expression of Mgat1 is up-regulated by TSH, insulin, and/or somatostatin.
ISSN:0300-9084
1638-6183
DOI:10.1016/j.biochi.2011.10.018