Puromycin aminonucleoside nephrosis (PAN) is a model for human
minimal change nephropathy induced in rats by injection of
puromycin. In PAN, defective sialylation of a major
sialoprotein of podocytes,
podocalyxin, has been demonstrated and the consequent decrease of anionic charge suggested as a causative factor for increased glomerular permeability and
proteinuria. Whether defective sialylation is a general feature of PAN affecting also glomerular
glycosphingolipids is not known. We have shown that rat glomeruli are rich in
disialogangliosides GD3 and O-acetyl GD3, the functions of which are not known. Here, we made a sequential analysis of the glomerular
gangliosides, especially of GD3 and its O-acetyl derivative in acute PAN using immunohistochemical and biochemical techniques and compared the results with another rat model of glomerular disease,
Heymann nephritis. The prominent immunohistochemical finding was the almost total disappearance of glomerular O-acetyl GD3 and a substantial decrease of its precursor GD3 peaking
at 10 days after injection of
puromycin. Segmental areas lacking these
gangliosides remained in glomeruli still at 30 days after injection. The response was dose dependent. Semiquantitative analysis by thin layer chromatograms showed that O-acetyl GD3 was decreased by 41% already at 3 days and by 60%
at 10 days after injection of
puromycin. Also GD3, the immediate precursor of O-acetyl GD3, was decreased by 20 and 19%, respectively, at 3 and 10 days after injection. At 3 days after injection, overt
proteinuria had not started. At these times, no other changes were observed in the glomerular
gangliosides. The decrease of glomerular GD3 and O-acetyl GD3 indicates a decrease of GD3 synthase activity and perhaps of O-
acetyltransferase activity in PAN
nephrosis. As these changes preceded the overt
proteinuria, they may have a causal relationship to it. In the glomeruli of Heymann nephritic rats, no similar changes were seen, suggesting that the sialylation defect is not due to
proteinuria but is a consequence of targeted
puromycin action on cells.