A specific structural alteration in the heparan sulphate of human glomerular basement membrane in diabetes.
OBJECTIVE
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-sulphatectl--> 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).


CONCLUSIONS
3-O-sulphated glucosamine is a rare constituent of heparan sulphate occurring usually in a glucuronic acidbeta1--> 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 acidalpha1--> 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.
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Department of Biological Chemistry, Harvard Medical School and the Joslin Diabetes Center, Boston, Mass., USA.
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D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001485:Basement Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D003920:Diabetes Mellitus / Q000378:metabolism* / Q000473:pathology; D004187:Disaccharides / Q000737:chemistry; D019812:Heparan Sulfate Proteoglycans / Q000032:analysis / Q000737:chemistry*; D006497:Heparan Sulfate / Q000737:chemistry*; D006801:Humans; D007678:Kidney Glomerulus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D012016:Reference Values
D004187:Disaccharides; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate