The protective effect of prostacyclin on adriamycin-induced apoptosis in rat renal tubular cells

Adriamycin-induced nephrosis in rats is a commonly used experimental model for pharmacological studies of human chronic renal diseases. Adriamycin-induced apoptosis of renal tubular cells has been reported in adriamycin-treated rats. In addition, prostacyclin (PGI(2)) is known to have various protective effects on many kinds of cells. To investigate the protective effect of PGI(2) on cells undergoing adriamycin-induced apoptosis, this study selectively augmented PGI(2) production via adenovirus-mediated transfer of genes for cyclooxygenase-1 (COX-1) and prostacyclin synthase (PGIS) (two key enzymes of PG12 synthesis) to renal tubular cells. This PG12 overexpression protected rat renal tubular cells from adriamycin-induced apoptosis. Ad-COX-1/PGIS transfection was found to reduce the adriamycin-stimulated activities of caspase-3 and caspase-9, inhibit adriamycin-induced release of cytochrome c, elevate the expression of Bcl-X-L, and suppress the activation and translocation of nuclear factor-kappaB (NF-kappa B) in adriamycin-treated renal tubular cells. Our results reveal that selective augmentation of PG12 production can protect rat renal tubular cells from adriamycin-induced apoptosis via the NF-kappa B signaling pathway. This implies the therapeutic potential of combined COX1 and PGIS gene transfer in gene therapy for chronic renal diseases. (c) 2005 Elsevier B.V. All rights reserved.