Cyclosporin A inhibits protein kinase C activity: a contributing mechanism in the development of nephrotoxicity?

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Updated: Sep 22, 2026

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

R J Walker1, V A Lazzaro, G G Duggin

  • 1Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown NSW, Australia.

Biochemical and Biophysical Research Communications
|April 14, 1989
PubMed

Insights

Cyclosporin A (CSA) inhibits protein kinase C activity in kidney cells, potentially explaining its nephrotoxicity. CSA also blocks phorbol ester-induced PGE2 release in rat mesangial cells, further implicating protein kinase C.

Area of Science:

  • Nephrology
  • Cell Biology
  • Pharmacology

Background:

  • Cyclosporin A (CSA) is known to affect various cellular functions.
  • The precise mechanisms underlying CSA-induced nephrotoxicity are not fully understood.
  • Protein kinase C (PKC) plays a role in cellular signaling and function.

Purpose of the Study:

  • To investigate the interaction between Cyclosporin A and protein kinase C.
  • To determine if PKC inhibition is a mechanism for CSA nephrotoxicity.
  • To explore CSA's effect on PKC-mediated signaling pathways.

Main Methods:

  • Assessed protein kinase C activity in the cytosol of renal epithelial cells.
  • Used 12-O-tetradecanoylphorbol-13-acetate (phorbol ester) to activate PKC in rat mesangial cells.
  • Measured prostaglandin E2 (PGE2) release in response to phorbol ester stimulation.
  • Quantified the inhibitory effects of CSA on PKC activity and PGE2 release.

Main Results:

  • Cyclosporin A significantly inhibited protein kinase C activity in renal epithelial cells in a dose-dependent manner.
  • CSA significantly inhibited phorbol ester-stimulated PGE2 release in cultured rat mesangial cells.
  • These findings suggest PKC is a key intracellular target for CSA.

Conclusions:

  • Protein kinase C is a likely intracellular target for Cyclosporin A.
  • Inhibition of protein kinase C may mediate CSA's effects on intracellular functions and contribute to nephrotoxicity.
  • Further research into the CSA-PKC interaction could reveal new therapeutic strategies.

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