Role of protein kinase A signaling pathway in cyclosporine nephrotoxicity.
Nenhuma Miniatura disponível
Data
2014
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
Cyclosporine is an important immunosuppressive agent; however, nephrotoxicity is one of the
main adverse effects. The purpose of this study was to evaluate the effect of inhibiting
the protein kinase A (PKA) signaling pathway in nephrotoxicity caused by cyclosporine from the
assessment of cell viability, pro-inflammatory cytokines, and nitric oxide (NO) production in
LLC-PK1 and MDCK cell lines. Cyclosporine proved to be cytotoxic for both cell lines, as
assessed by the mitochondrial enzyme activity assay (MTT), caused DNA fragmentation,
determined by flow cytometry using the propidium iodide dye, and activated the PKA pathway
(western blot assay). In MDCK cells, the inhibition of the PKA signaling pathway (H89 inhibitor)
caused a significant reduction in DNA fragmentation. In both cell lines, the production of IL-6
proved to be a dependent PKA pathway, while TNF-a was not influenced by the inhibition of
the PKA pathway. The NO production was increased when cells were pre-incubated with H89
followed by cyclosporine, and this production was dependent on the PKA pathway in LLC-PK1
and MDCK cells lines. Therefore, considering the present study’s results, it can be concluded
that the inhibition of PKA signaling pathway can aid in reducing the degree of nephrotoxicity
caused by cyclosporine.
Descrição
Palavras-chave
Citação
FRANÇA, F. D. et al. Role of protein kinase A signaling pathway in cyclosporine nephrotoxicity. Toxicology Mechanisms and Methods, v. 24, p. 369-376, 2014. Disponível em: <http://www.tandfonline.com/doi/abs/10.3109/15376516.2014.920447?journalCode=itxm20>. Acesso em: 19 fev. 2017.