caa a22 4500 475772555 CHVBK 20180406123621.0 cr unu---uuuuu 170329e20000801xx s 000 0 eng 10.1007/s001250051489 doi (NATIONALLICENCE)springer-10.1007/s001250051489 A specific structural alteration in the heparan sulphate of human glomerular basement membrane in diabetes [Elektronische Daten] [A. S. B. Edge, R. G. Spiro] Aims/hypothesis. Heparan sulphate proteoglycan is an important component of the glomerular anionic filtration barrier and its reduced amount in diabetes contributes to glomerular dysfunction. The objective of this study was to determine if there is also an alteration in the sulphation pattern of the diabetic heparan sulphate chains. Methods. The heparan sulphate in the glomerular basement membrane/mesangial matrix from human diabetic and nondiabetic kidneys obtained at autopsy was fragmented by a hydrazine/nitrous acid procedure and after radiolabelling with NaB[3H]4, the disaccharide products were chromatographically resolved and quantified. Results. Six sulphated disaccharides were identified in both the diabetic and nondiabetic samples and the molar distribution of these was similar, with the notable exception of the iduronic acid-2-O-sulphateα1 → 4glucosamine-3-O-sulphate species which occurred in the diabetic glomeruli in less than half the amount as in the nondiabetic samples (9.0 % compared to 18.7 % of total sulphated disaccharides, p < 0.005). Conclusion/interpretation. 3-O-sulphated glucosamine is a rare constituent of heparan sulphate occurring usually in a glucuronic acidβ1 → 4glucosamine-3-O-sulphate( ± 6-O-sulphate) sequence within the antithrombin-binding domain. In the glomerular basement membrane where the 3-O-sulphated glucosamine is present in substantial amounts, however, it occurs exclusively in an iduronic acid-containing sequence. It is likely that the recently discovered 3-O-sulphotransferase variant which specifically acts on the iduronic acidα1 → 4glucosamine sequence is decreased in human diabetes and moreover that this unusual disaccharide could be a component of a specific heparan sulphate domain which interacts with bioactive proteins. [Diabetologia (2000) 43: 1056-1059] Springer-Verlag Berlin Heidelberg, 2000 Keywords Glomerular basement membrane nationallicence diabetic glomerular basement membrane alterations nationallicence 3-O-sulphated glucosamine nationallicence heparan sulphate binding nationallicence heparan sulphate sulphation sites nationallicence hydrazine/nitrous acid fragmentation nationallicence iduronic acid nationallicence glomerular anionic filter nationallicence Edge A. S. B. Departments of Biological Chemistry and Medicine, Harvard Medical School and the Joslin Diabetes Center, Boston, Mass., USA, US aut Spiro R. G. Departments of Biological Chemistry and Medicine, Harvard Medical School and the Joslin Diabetes Center, Boston, Mass., USA, US aut https://doi.org/10.1007/s001250051489 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250051489 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Edge A. S. B. Departments of Biological Chemistry and Medicine, Harvard Medical School and the Joslin Diabetes Center, Boston, Mass., USA, US aut NATIONALLICENCE 700 1- Spiro R. G. Departments of Biological Chemistry and Medicine, Harvard Medical School and the Joslin Diabetes Center, Boston, Mass., USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer