Renal epithelial gene expression profile and bismuth-induced resistance against cisplatin nephrotoxicity.
Nephrotoxicity is the most important dose-limiting factor in cisplatin based anti-neoplastic treatment. Pretreatment with bismuth salts, used as pharmaceuticals to treat gastric disorders, has been demonstrated to reduce cisplatin-induced renal cell death in clinical settings and during in vivo and in vitro animal experiments. To investigate the genomic basis of this renoprotective effect, we exposed NRK-52E cells, a cell line of rat proximal tubular epithelial origin, to 33 microM Bi3+ for 12 hours, which made them resistant to cisplatin-induced apoptosis. Differentially expressed genes in treated and untreated NRK-52E cells were detected by subtraction PCR and microarray techniques. Genes found to be down regulated (0.17-0.31-times) were cytochrome c oxidase subunit I, BAR (an apoptosis regulator), heat-shock protein 70-like protein, and three proteins belonging to the translation machinery (ribosomal proteins S7 and L17, and S1, a member of the elongation factor 1-alpha family). The only up-regulated gene was glutathione S-transferase subunit 3A (1.89-times). Guided by the expression levels of these genes, it may be possible to improve renoprotective treatments during anti-neoplastic therapies.
Leussink
Berend T
BT
Toxicology Laboratory, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands.
Baelde
Hans J
HJ
Broekhuizen-van den Berg
Thirza M
TM
de Heer
Emile
E
van der Voet
Gijsbert B
GB
Slikkerveer
Anja
A
Bruijn
Jan A
JA
de Wolff
Frederik A
FA
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D001729:Bismuth / Q000627:therapeutic use*; D002478:Cells, Cultured; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007687:Kidney Tubules, Proximal / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction; D051381:Rats
D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D002945:Cisplatin; D001729:Bismuth