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Updated: Apr 30, 2026

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

Published on: January 7, 2013

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Role of protein kinase A signaling pathway in cyclosporine nephrotoxicity

F D França1, A F Ferreira, R C Lara

  • 1Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte - MG , Brasil .

Toxicology Mechanisms and Methods
|May 3, 2014
PubMed

Insights

Inhibiting the protein kinase A (PKA) pathway may reduce cyclosporine-induced kidney damage. This study found PKA inhibition lessened cell death and altered inflammatory markers, suggesting a protective effect against nephrotoxicity.

Area of Science:

  • Nephrology
  • Molecular Pharmacology
  • Cell Biology

Background:

  • Cyclosporine is a vital immunosuppressant with significant nephrotoxicity.
  • The protein kinase A (PKA) signaling pathway's role in cyclosporine-induced kidney damage is not fully understood.

Purpose of the Study:

  • To investigate the impact of inhibiting the PKA signaling pathway on cyclosporine-induced nephrotoxicity.
  • To assess effects on cell viability, pro-inflammatory cytokines (IL-6, TNF-α), and nitric oxide (NO) production.

Main Methods:

  • Utilized LLC-PK1 and MDCK cell lines.
  • Assessed cell viability via MTT assay.
  • Measured DNA fragmentation using flow cytometry (propidium iodide).
  • Analyzed PKA pathway activation and cytokine levels via western blot.

Main Results:

  • Cyclosporine induced cytotoxicity, DNA fragmentation, and PKA activation in both cell lines.
  • PKA inhibition (H89) significantly reduced DNA fragmentation in MDCK cells.
  • IL-6 production was PKA-dependent, while TNF-α was not affected.
  • NO production increased with H89 pre-incubation followed by cyclosporine, dependent on the PKA pathway.

Conclusions:

  • Inhibition of the PKA signaling pathway shows potential in mitigating cyclosporine-induced nephrotoxicity.
  • Targeting PKA may offer a therapeutic strategy to reduce kidney damage associated with cyclosporine treatment.
Keywords:
CyclosporineIL-6NOPKATNF-αnephrotoxicity

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