THE CYCLOSPORINE-A-INDUCED DECREASE IN RAT RENAL CALBINDIN-D28KDA PROTEIN AS A CONSEQUENCE OF A DECREASE IN ITS MESSENGER-RNA

Cyclosporine A (CsA) is a potent immunosuppressant with the drawback o f renal side-effects. We recently reported that relatively high doses of CsA markedly decreased the calcium binding protein calbindin-D28kDa in kidneys of male Wistar rats, and showed that this decrease could b e associated with some of the drug-induced adverse renal effects. To i nvestigate the events leading to this decrease, the calbindin-D28kDa m RNA level in kidneys of rats treated with 15 or 50 mg/kg/day CsA for 1 2 days was analysed by reverse transcription followed by polymerase ch ain reaction. At both doses, a marked dose-dependent decrease in the c albindin-D28kDa mRNA level was found, one very similar to the decrease measured in the calbindin-D28kDa protein abundance. Thus, the CsA-med iated down-regulation of the renal calbindin-D28kDa protein is most li kely the result of a decrease in the calbindin-D28kDa mRNA level. (C) 1998 Elsevier Science Inc.