Activity of calcium-sensitive phospholipid-dependent protein kinase C following nephron loss

Abstract

The localization and activity of the calcium-sensitive phospholipid-dependent protein kinase C (PKC) were examined following the loss of 50% of functioning nephron mass. Four hours following unilateral nephrectomy in rats, soluble (100,000 g supernatant) proteins in the contralateral kidney were increased by 11% compared to sham operated controls; the increase was 33% 144 hours following surgery. The specific activity of PKC did not change in the cytosol at any of the time periods examined and averaged 63.9 +/- 8.2 pmol.mg-1.min-1 in unilaterally nephrectomized animals four hours following surgery. Four hours following sham surgery total soluble PKC activity averaged 1667.0 +/- 278.4 pmol.kidney-1.min-1, whereas activity averaged 3067.7 +/- 415.4 pmol.kidney-1.min-1 in animals post-nephrectomy (N = 5, P less than 0.04). Similar data was seen 144 hours following surgery. To examine the PKC activity in plasma membranes of proximal tubular cells, brush border membranes were prepared from rat kidney cortex. Twenty-four hours following unilateral nephrectomy, activity averaged 193.8 +/- 14.9 pmol.mg-1.min-1, while activity in membranes isolated from sham operated animals averaged 76.6 +/- 8.0 pmol.mg-1.min-1 (N = 5, P less than 0.001). Similar data was evident 48 hours following surgery. A small increment in activity was seen in the basolateral membrane preparation 24 hours following unilateral nephrectomy but not at 48 hours. These data indicate that cellular PKC activity increases rapidly following reductions in renal mass, and there are selective increments in the brush border membrane of the proximal tubular cell. The localization of PKC to this membrane may have important consequences for adaptations following nephron loss.