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

Abstract：

: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 PGI(2) synthesis) to renal tubular cells. This PGI(2) 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-kappaB) in adriamycin-treated renal tubular cells. Our results reveal that selective augmentation of PGI(2) production can protect rat renal tubular cells from adriamycin-induced apoptosis via the NF-kappaB signaling pathway. This implies the therapeutic potential of combined COX-1 and PGIS gene transfer in gene therapy for chronic renal diseases.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Chen CH,Lin H,Hsu YH,Sue YM,Cheng TH,Chan P,Chen TH

doi

10.1016/j.ejphar.2005.10.057

keywords:

subject

Has Abstract

pub_date

2006-01-04 00:00:00

pages

8-15

issue

1-3

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(05)01100-3

journal_volume

529

pub_type

杂志文章

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