The Role of Na~+/Ca~(2+) Exchanger in Endothelin-1-Aggravated Hypoxia/Reoxygenation-Induced Injury in Renal Epithelial Cells

摘要

We analyzed the role of the Na~+/Ca~(2+) exchanger (NCX) in endothelin-1-aggravated hypoxia/reoxygenation-induced injury in renal epithelial LLC-PK_1 cells. KB-R7943, a selective NCX inhibitor, suppressed hypoxia/reoxygenation-induced cell damage, whereas over-expression of NCX1 into cells enhanced it. Endothelin-1 significantly aggravated hypoxia/reoxygenation-induced injury in parental and NCX1-overexpressing LLC-Pki cells. Such aggravation by endothelin-1 was not observed in cells overexpressing a deregulated NCX1 mutant, which displays no protein kinase C-dependent activation. These results suggest that Ca~(2+) overload via NCX plays a critical role in hypoxia/reoxygenation-induced renal tubular injury, and that endothelin-1 aggravates the cell damage through the activation of NCX.