Selection of insulin-producing rat insulinoma (RINm) cells with improved resistance to oxidative stress.
The defense system against reactive oxygen species is believed to be crucial for the survival of insulin-producing cells after various injuries. The aim of our study was to select a subpopulation of insulin-producing RINm cells with higher resistance to oxidative stress. The cells resistant to hydrogen peroxide (RINmHP) were obtained by repeated exposure of parental RINm cells to 100 and 200 microM hydrogen peroxide (HP). The increased resistance of RINmHP cells to HP was confirmed by three different cytotoxicity assays. In addition, the selected cells also were resistant to the cytotoxic effect of activated rat splenocytes compared to parental cells. The half-life of HP in the RINmHP cell culture medium was about 2.5 times lower than that of the parental cells, corresponding to the increased level of catalase expression and activity in selected cells. The increased defense property of the selected cells was not associated with any significant changes in insulin content and insulin response to a mixture of glucose with isobutyl methyl xanthine or potassium chloride. In conclusion, repeated exposure to HP induces selection of RINm cells with improved resistance to oxidative stress. This improved defense characteristic probably is due to an increased level of catalase expression and activity in the selected cells.
Bloch
Konstantin O
KO
Diabetes and Obesity Research Laboratory, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petah Tikva, Israel. kbloch@post.tau.ac.il
Vorobeychik
Marina
M
Yavrians
Karina
K
Vardi
Pnina
P
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007340:Insulinoma / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D014118:Toxins, Biological / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007328:Insulin; D014118:Toxins, Biological; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase