Abstract
Immunosuppressant such as cyclosporine A and tacrolimus is used to suppress the immune response for the therapeutic purposes of organ and tissue transplantation. However, clinical application of these drugs is limited by severe side effects. One of harmful effect is hypomagnesemia which may be caused by a reduction of renal magnesium reabsorption. In the present study, we examined the effect of cyclosporine A on the expression of magnesium channel TRPM6 and TRPM7 in renal epithelial NRK-52 cells. In RT-PCR and Western blotting analysis, cyclosporine A dose-dependently decreased in TRPM6 without TRPM7. The addition of extracellular MgCl2 under the Mg2+-free conditions caused an increase of intracellular free Mg2+ concentration ([Mg2+]i). The increase of [Mg2+]i was significantly inhibited by cyclosporine A. Gene silencing using siRNA against TRPM6 caused a decrease of TRPM6 without TRPM7. The increase in [Mg2+]i caused by MgCl2 addition was inhibited by siRNA transfection. Next, we investigated the effect of cyclosporine A on the expression of transcriptional factors, c-fos and c-jun. Cyclosporine A dose-dependently decreased in c-fos without c-jun. We suggest that cyclosporine A causes the reduction of renal magnesium reabsorption mediated by decrease in TRPM6 and c-fos expressions, resulting in a hypomagnesemia. [J Physiol Sci. 2007;57 Suppl:S127]
