DECREASE OF GLOMERULAR DISIALOGANGLIOSIDES IN PUROMYCIN NEPHROSIS OF THE RAT

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, podocalyx in, has been demonstrated and the consequent decrease of anionic charg e suggested as a causative factor for increased glomerular permeabilit y and proteinuria. Whether defective sialylation is a general feature of PAN affecting also glomerular glycosphingolipids is not known, We h ave shown that mt glomeruli are rich in disialogangliosides GD(3) and O-acetyl GD(3) the functions of which are not known, Here, we made a s equential analysis of the glomerular gangliosides, especially of GD(3) and its O-acetyl derivative in acute PAN using immunohistochemical an d biochemical techniques and compared the results with another rat mod el of glomerular disease, Heymann nephritis. The prominent immunohisto chemical finding was the almost total disappearance of glomerular O-ac etyl GD(3) and a substantial decrease of its precursor GD(3) peaking a t 10 days after injection of puromycin. Segmental areas lacking these gangliosides remained in glomeruli still at 30 clays after injection, The response was dose dependent. Semiquantitative analysis by thin lay er chromatograms showed that O-acetyl GD(3) was decreased by 41% alrea dy at 3 days and by 60% at 10 days after injection of puromycin. the i mmediate precursor of O-acetyl Also GD(3), the immediate precursor of O-acetyl GD(3), was decreased by 20 and 19%, respectively, at 3 and 10 days after injection. At 3 days after injection, overt proteinuria ha d not started. At these times, no other changes were observed in the g lomerular gangliosides. The decrease of glomerular GD(3) and O-acetyl GD(3) indicates a decrease of GD(3) synthase activity and perhaps of O -acetyltransferase activity in PAN nephrosis, As these changes precede d 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.