A prostacyclin analog beraprost sodium attenuates radiocontrast media-induced LLC-PK1 cells injury

Takahisa Yano, Yoshinori Itoh, Toshio Kubota, Toshiaki Sendo, Ryozo Oishi

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Background. We previously reported that the apoptotic injury in a porcine renal tubular cell line LLC-PK1 cells induced by radiographic contrast media is attenuated by dibutyl cyclic adenosine monophosphate (cAMP) in a manner dependent on protein kinase A (PKA). The present study was designed to determine whether the elevation of endogenous cAMP with beraprost sodium, a prostacyclin analog, reduces the contrast material-induced renal tubular injury. Methods. The cell injury was induced by the exposure to ioversol for 30 minutes followed by further incubation for 24 hours in the absence of the contrast medium, and assessed by propidium iodide uptake and WST-8 assay. Apoptosis was determined by annexin V stain and DNA electrophoresis. Caspase activity was assessed by the enzymatic degradation of specific substrate peptides. Bax and bcl-2 mRNA expression were determined by reverse transcription-polymerase chain reaction (RT-PCR). The phosphorylation of cAMP-responsive element binding protein (CREB) was measured by an immunofluorescent method. Results. Beraprost sodium (10 to 1000 nmol/L) attenuated concentration dependently the ioversol-induced decrease in cell viability, in which the protective effect of beraprost sodium was dependent on the elevation of cellular cAMP content. The phosphorylation of CREB was enhanced by beraprost sodium in PKA-dependent manner. In addition, beraprost sodium reversed the ioversol-induced increase in bax mRNA with a concomitant decrease in bcl-2 mRNA and subsequent activation of caspase-3 and -9, thereby resulting in the inhibition of the nuclear damage. Conclusion. Beraprost sodium reversed the contrast media-induced renal tubular cells in culture by activating cAMP/protein kinase A-dependent phosphorylation of CREB and subsequent enhancement of bcl-2 expression.

Original languageEnglish
Pages (from-to)1654-1663
Number of pages10
JournalKidney International
Volume65
Issue number5
DOIs
Publication statusPublished - May 2004

Keywords

  • Apoptosis
  • Prostacyclin
  • Protein kinase A
  • Radiographic contrast media
  • Renal tubular cells
  • cAMP
  • cAMP response element binding protein

ASJC Scopus subject areas

  • Nephrology

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