Action of cyclosporine on mitochondrial calcium fluxes
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Cyclosporine (Cys A) is a potent immunosuppressor used to reduce rejection in transplantation surgery. We studied its action upon mitochondrial functions: oxidative phosphorylation and Ca2+ movements through mitochondrial membrane. We show that Cys A exhibits an inhibitory effect upon mitochondrial respiration. This result is in good agreement with previous works and may be correlated with Cys A toxicity. The action of cyclosporine on calcium fluxes is more pronounced. Indeed it blocks mitochondrial calcium efflux and allows mitochondria to accumulate a large amount of calcium. If this effect occurs in the cell, it would induce a Ca2+ decrease in cytosol. This action might be correlated with the inhibitory effect of Cys A upon the mitogenic stimulation of T lymphocytes.
- Borel, J. F., Feurer, C., Magnee, C., and Stahelin, H. (1977). Effect of the new antilymphocyte peptide Cyclosporine A in animals,Immunology 32, 1017.
- Caine, R. Y. (1979). Immunosuppression for organ grafting. Observation on Cyclosporine A,Immunol. Rev. 46, 113.
- Chance, B., and William, G. R. (1956). The respiratory chain and oxidative phosphorylation,Adv. Enzymol. 17, 65.
- Ducet, G., Gidrol, X., and Richaud, P. (1983). Membrane potential changes in coupled potato mitochondria,Physiol. Veg. 21, 385.
- Ferrero, M. E., and Marni, A. (1985). The effect of Cyclosporine on nucleotide content of rat lymphocytes,Int. J. Immunopharmacol. 7, 897.
- Fiskum, G. (1984).Metal Ions in Biological Systems. Volume 17:Calcium and Its Role in Biology, Marcel Dekker, New York and Basel, p. 187.
- Hay, R., Tammi, K., Ryffel, B., and Mihatsch, M. J. (1986). Alterations in molecular structure of renal mitochondria associated with Cyclosporine A treatment,Clin. Nephrol. 25, Suppl. 1, S 23.
- Johnson, G., and Lardy, H. A. (1967). Isolation of liver or kidney mitochondria,Methods Enzymol. 10, 94.
- Jung, K., and Pergande, M. (1985). Influence of Cyclosporine A on the respiration of isolated rat kidney mitochondria,FEBS Lett. 183, 167.
- Kamo, N., Mutatsugu, M., Hongoh, R., and Kobatake, Y. (1979). Membrane potential of mitochondria measured with an electrode sensitive to tetraphenylphosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state,J. Membr. Biol. 49, 105.
- Kay, J. E., Benzie, C. R., and Borghetti, A. F. (1983). Effect of Cyclosporine A on lymphocyte activation by the calcium ionophore A 23187,Immunology 50, 441.
- Morris, P. J. (1981). Cyclosporine A,Transplantation 32, 349.
- Nicchitta, C. V., Kamoun, M., and Williamson, J. R. (1985). Cyclosporine augments receptor-mediated cellular Ca2+ fluxes in isolated hepatocytes,J. Biol. Chem. 260, 13613.
- Tsien, R. Y., Pozzan, T., and Rink, T. J. (1982). T cell mitogens cause early changes in cytoplasmic free Ca2+ membrane potential in lymphocytes,Nature (London)295, 68.
- Verpooten, G. A., Wybo, I., Pattyn, V. M., Hendrix, P. G., Giuliano, R. A., Nouwen, E. J., Roels, F., and de Broe, M. E. (1986). Cyclosporine nephrotoxicity: comparative cytochemical study of rat kidney and human allograft biopsies,Clin. Nephrol. 25, Suppl. 1, S 18.
- Wright, B., Greig, R., and Poste, G. (1984). Inhibition of macrophage activation and tumor cell cytolysis by Cyclosporine A,Biochem. Biophys. Res. Commun. 123, 710.
- Action of cyclosporine on mitochondrial calcium fluxes
Journal of Bioenergetics and Biomembranes
Volume 19, Issue 3 , pp 297-303
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