Puromycin aminonucleoside (NSC-3056) increases podocyte permeability by modulating ZO-1 in an oxidative stress-dependent manner.

Puromycin aminonucleoside -induced podocyte apoptosis is p53 dependent. Puromycin aminonucleoside causes podocyte apoptosis in a time-dependent manner. The IC50 values for PMAT-expressing and vector-transfected cells are 48.9 and 122.1 μM, respectively, suggesting expression of PMAT-enhanced cell sensitivity to Puromycin aminonucleoside. Puromycin aminonucleoside uptake in PMAT-expressing cells is fourfold higher at pH 6.6 than that at pH 7.4. Puromycin aminonucleoside (30 μg/mL) markedly enhances p53 protein levels in podocytes. Puromycin aminonucleoside (250 μM) is toxic to both PMAT-expressing and vector-transfected cells [2][4].

Rats administered Puromycin aminonucleoside (100 mg/kg, s.c.) exhibited reduced weight gain and elevated serum creatinine levels compared to controls. The podocyte count per glomerulus in control rats stood at 95.5±17.6, dropping to 90.7 by Day 4 in rats with Puromycin aminonucleoside (8 mg/100 g, i.v.)-induced nephrosis. Furthermore, nephrin levels per glomerulus in controls were 1.02±0.11 fmol, which decreased significantly in nephrosis rats to 0.46±0.06 fmol and 0.35±0.04 fmol on Days 4 and 7, respectively. This reduction in nephrin per podocyte was closely linked to proteinuria development in rats affected by Puromycin aminonucleoside nephrosis [5][6].