Oxidant-induced cell death in renal epithelial cells: differential effects of inorganic and organic hydroperoxides.
This study was undertaken in order to examine the roles of lipid peroxidation and poly (ADP-ribose) polymerase (PARP) activation in oxidant-induced renal cell death. Opossum kidney cell cultures were used as the renal epithelial cell model, and an inorganic hydroperoxide H2O2 and an organic hydroperoxide t-butylhydroperoxide were employed as model oxidants. Cell death by both oxidants could be prevented by thiols (dithiothreitol and glutathione), iron chelators (deferoxamine and phenanthroline), and hydroxyl radical scavengers (dimethylthiourea and pyruvate). Phenolic antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD) and butylated hydroxyanisole had no effect on the H2O2-induced cell death. However, the t-butylhydroperoxide-induced cell death was effectively prevented by these antioxidants. The PARP inhibitor 3-aminobenzamide prevented the cell death induced by H2O2, but not cell death by t-butylhydroperoxide. The PARP activity was increased in cells exposed to H2O2 but not t-butylhydroperoxide. Unlike in opossum kidney cells, in rabbit renal cortical slices both oxidants H2O2 and t-butylhydroperoxide induced cell death through a lipid peroxidation-dependent and PARP-independent mechanism. Effects of DPPD and 3-aminobenzamide on H2O2-induced cell death in primary cultured rabbit proximal tubular cells were similar to those in opossum kidney cells. These results indicate that 1) the H2O2-induced cell death in cultured renal epithelial cells is associated with PARP activation but not lipid peroxidation, whereas the t-butylhydroperoxide-induced cell death is mediated by lipid peroxidation, and 2) the role of lipid peroxidation in H2O2 cytotoxicity may be different between freshly isolated renal tubular cells and cultured renal epithelial cells.
Park
Sung Min
SM
Department of Internal Medicine, College of Medicine, Pusan National University, Pusan, Korea.
Jung
Hyun Chul
HC
Koak
Im Soo
IS
Na
Ha Yun
HY
Woo
Jae Suk
JS
Jung
Jin Sup
JS
Kim
Yong Keun
YK
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology* / Q000187:drug effects; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009893:Opossums; D016877:Oxidants / Q000633:toxicity*; D010545:Peroxides / Q000633:toxicity*; D010655:Phenylenediamines / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011817:Rabbits; D020122:tert-Butylhydroperoxide / Q000633:toxicity
D001549:Benzamides; D002614:Chelating Agents; D016877:Oxidants; D010545:Peroxides; D010655:Phenylenediamines; C025160:3-aminobenzamide; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide; C004845:N,N'-diphenyl-4-phenylenediamine; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases