Glomerular basement membrane heparan sulfate glycosaminoglycan in aminonucleoside of puromycin nephrosis.

Proteinuria in aminonucleoside of puromycin (PAN) nephrosis is due to an alteration of the glomerular charge- and size-selective barrier. Heparan sulfate seems to play a role in glomerular charge permeability to plasma proteins. We report a quantitative analysis and metabolism of glomerular basement membrane (GBM) heparan sulfate in PAN nephrosis. Studies were performed 5 and 10 days post-PAN administration (15 mg/100 g) to Sprague-Dawley rats. GBM heparan sulfate glycosaminoglycan was measured using the dimethylmethylene blue test after chromatographic separation of the digested GBM. Sulfate-35 uptake by GBM and catabolism of GBM-sulfated compounds were studied using glomerular cultures. The heparan sulfate glycosaminoglycans concentration on day 5 (1.42 micrograms/mg GBM protein) was within the normal range (1.17 +/- 0.25), but the concentration on day 10 was below the limit of detection (0.57 micrograms/mg). The sulfate-35 incorporated in the GBM glycosaminoglycan on day 5 (158 cpm/micrograms glycosaminoglycan) was lower than the uptake of control GBM (270 cpm/micrograms glycosaminoglycan), and markedly lower than the uptake on day 10 (1,590 cpm/micrograms glycosaminoglycan). The catabolism of the GBM sulfated compounds on day 5 and 10 was not different than the one seen in controls. These data suggest that PAN administration is associated with a decrease in synthesis of GBM-sulfated compounds on day 5 and a decrease in GBM heparan sulfate glycosaminoglycan on day 10. However, on day 10, an increased compensatory synthesis is observed. This may subsequently normalize the GBM heparan sulfate concentration and explain the resolution of the proteinuria.