Roles of NF-κB and Bcl-2 in Two Differential Modes of Cell Death of Mouse Cortical Collecting Duct Cells

Abstract

Recent data have implicated nuclear factor-ĸB (NF-ĸB) and Bcl-2 in the regulation of apoptotic and necrotic cell death in various cells. However, mechanisms of their effects on cell death of renal epithelial cells are not clear. First, we investigated the effect of specific inhibition of NF-ĸB and overexpression of Bcl-2 on necrotic cell death induced by hydrogen peroxide or cisplatin in renal collecting duct cells. M-1 cells, which were derived from outer cortical collecting duct, were stably transfected with the non-phosphorylatable mutant of inhibitory-ĸBα (I-ĸBα) and Bcl-2. Overexpression of I-ĸBα and Bcl-2 did not affect cisplatin-induced necrotic cell death, but overexpression of I-ĸBα significantly decreased H₂O₂-induced cell death. Regarding apoptotic cell death induced by cisplatin, serum deprivation and contact inhibition was increased by overexpression of I-ĸBα, whereas overexpression of bcl-2 inhibited the apoptotic cell death. I-ĸBα overexpression increased Bax expression and decreased cIAP-1 and -2 expression compared to vector-transfected cells, but did not alter SAPK/JNK activity in the presence or absence of cisplatin. NF-ĸB activity was significantly higher in bcl-2-overexpressing cells than in control cells. These data show that activation of NF-ĸB mediates H₂O₂-induced necrotic injury, but inhibits apoptotic cell death in renal collecting duct cells, and that Bcl-2 selectively protects apoptotic cell death in M-1 cells.