Cytosolic calcium and protein kinase C reduce complement-mediated glomerular epithelial injury

Kidney Int. 1990 Nov;38(5):803-11. doi: 10.1038/ki.1990.274.


In rat membranous nephropathy, protein-uria is due to formation of the C5b-9 membrane attack complex of complement (C), and is associated with morphological evidence of glomerular epithelial cell (GEC) injury. Analogous morphological changes are induced by C5b-9 in cultured GEC. In addition, in cultured GEC C5b-9 induces Ca2+ influx, as well as Ca2+ mobilization and increased 1,2-diacylglycerol due to the activation of phospholipase C. In this study we investigated how this GEC activation pattern might influence C-mediated GEC injury. We demonstrate that the C5b-9-induced increase in cytosolic Ca2+ concentration ([Ca2+]i) did not impair ATP generation by mitochondria, suggesting that it does not contribute to cytotoxicity. Moreover, this increase in [Ca2+]i protected GEC from C-mediated cytolysis. However, a large increase in [Ca2+]i (produced by the Ca2+ ionophore A23187) impaired ATP generation and aggravated C-mediated cytotoxicity, suggesting that intact mitochondrial activity is necessary for GEC to withstand C attack. Activation of protein kinase C (PKC) by phorbol myristate acetate (PMA) also decreased C-mediated cytolysis. Conversely, C lysis was enhanced in GEC that had been pretreated for 18 hours with a high dose of PMA to deplete PKC, and following PKC inhibition with H-7. Therefore, PKC activation, possibly resulting from C5b-9-induced increase in 1,2-diacylglycerol, triggered mechanisms that protected GEC from C-mediated injury. Thus, as a consequence of C5b-9-induced phospholipase activation, the amount of C-induced GEC injury is diminished.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Calcium / pharmacology*
  • Cell Survival
  • Complement Membrane Attack Complex / immunology*
  • In Vitro Techniques
  • Kidney Glomerulus / immunology*
  • Kidney Glomerulus / pathology
  • Phospholipases / metabolism
  • Protein Kinase C / pharmacology*
  • Rats


  • Complement Membrane Attack Complex
  • Adenosine Triphosphate
  • Protein Kinase C
  • Phospholipases
  • Calcium