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 given Puromycin aminonucleoside (100 mg/kg, s.c.) gain less weight and their serum creatinine levels are higher than the control rats. The number of podocytes per glomerulus is 95.5±17.6 in the control rats, 90.7 on Day 4 in Puromycin aminonucleoside (8 mg/100 g, i.v.)-treated nephrosis rats. The amount of nephrin per glomerulus in control rats is 1.02±0.11 fmol and those in Puromycin aminonucleoside nephrosis rats are reduced to 0.46±0.06 fmol and 0.35±0.04 fmol on Day 4 and Day 7. The nephrin amount per podocyte is significantly decreased association with the development of proteinuria in Puromycin aminonucleoside nephrosis rats [5][6].