Inhibition of chondroitin sulfate incorporation into human thyroglobulin by p-nitrophenyl-beta-D-xylopyranoside

Endocrinology
L Fogelfeld, A B Schneider

Abstract

Human thyroglobulin (TG) is unique among glycoproteins and TGs of other species in having a chondroitin sulfate chain. We studied the effects of p-nitrophenol-beta-D-xylopyranoside (PNXP), an inhibitor of chondroitin sulfate incorporation into core protein of proteoglycans, on the synthesis of human TG. Fragments of normal thyroid tissue from two patients were preincubated for 1 h with PNXP before adding [35S] sulfate and [3H]leucine. TG was purified by ammonium sulfate precipitation, sucrose gradient centrifugation, and CsCl equilibrium density gradient centrifugation. Chondroitin ABC lyase released 38-42% of the [35S]sulfate from control TG, synthesized in the absence of inhibitor, demonstrating the presence of chondroitin sulfate units. In the samples incubated with increasing concentrations of PNXP (0.2 and 1 mM), the fraction of [35S] sulfate released by ABC lyase decreased progressively (14-23% and 8-11%, respectively). This confirms that, as in chondroitin sulfate proteoglycans, chondroitin sulfate synthesis in TG is initiated by the transfer of a galactose unit, by galactosyltransferase, to a xylosyl-serine in the TG peptide backbone. This step is prevented by PNXP, which is a competitive acceptor of galactose. The dens...Continue Reading

Citations

Feb 1, 1997·Thyroid : Official Journal of the American Thyroid Association·P ArvanS Abu Hossain
Nov 22, 2019·Molecular and Cellular Endocrinology·Héctor M TargovnikCarina M Rivolta
Mar 11, 2021·Molecular and Cellular Endocrinology·Cintia E CitterioHéctor M Targovnik

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