The cyclosporine A-induced decrease in rat renal calbindin-D28kDa protein as a consequence of a decrease in its mRNA.
Cyclosporine A (CsA) is a potent immunosuppressant with the drawback of 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 be associated with some of the drug-induced adverse renal effects. To investigate the events leading to this decrease, the calbindin-D28kDa mRNA level in kidneys of rats treated with 15 or 50 mg/kg/day CsA for 12 days was analysed by reverse transcription followed by polymerase chain reaction. At both doses, a marked dose-dependent decrease in the calbindin-D28kDa mRNA level was found, one very similar to the decrease measured in the calbindin-D28kDa protein abundance. Thus, the CsA-mediated down-regulation of the renal calbindin-D28kDa protein is most likely the result of a decrease in the calbindin-D28kDa mRNA level.
Grenet
O
O
Preclinical Safety, Novartis Pharma AG, Basel, Switzerland.
Varela
M C
MC
Staedtler
F
F
Steiner
S
S
D000818:Animals; D064026:Calbindins; D016572:Cyclosporine / Q000494:pharmacology*; D003864:Depression, Chemical; D004797:Enzyme-Linked Immunosorbent Assay; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis* / Q000235:genetics
D064026:Calbindins; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D016572:Cyclosporine