Sildenafil Inhibits Advanced Glycation End Products-induced sFlt-1 Release Through Upregulation of Heme Oxygenase-1
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Á¤ÀçÇõ(Jeong Jae-Hyeok) - Pusan National University School of Medicine Department of Obstetrics and Gynecology
±èÈÖ°ï(Kim Hwi-Gon) - Pusan National University School of Medicine Department of Obstetrics and Gynecology
(Choi Ook-Hwan) - Pusan National University School of Medicine Department of Obstetrics and Gynecology
Abstract
Objectives: We examined the effect of sildenafil citrate on advanced glycation end products (AGEs)-induced soluble fms-like tyrosine kinase 1 (sFlt-1) release in JEG-3 choriocarcinoma cells.
Methods: Cells were incubated with control bovine serum albumin (BSA) or AGEs-BSA, and expression of sFlt-1 mRNA and protein release was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. AGEs-BSA increased sFlt-1 mRNA expression and protein release in a dose-dependent manner.
Results: Sildenafil citrate suppressed sFlt-1 mRNA expression and protein release in cells treated with AGEs-BSA in a dose-dependent manner. Likewise, it inhibited the increase of reactive oxygen species (ROS) production and NF-¥êB activity in these cells. Cobalt protoporphyrin (CoPP) and bilirubin also inhibited sFlt-1 release and ROS production in cells treated with AGEs-BSA, whereas zinc protoporphyrin IX (ZnPP IX) antagonized the effect of sildenafil citrate. In cells transfected with the heme oxygenase-1 (HO-1) siRNA, sildenafil citrate failed to inhibit the sFlt-1 release and ROS production.
Conclusion: These results strongly suggest that sildenafil citrate inhibits sFlt-1 release and ROS production in cells treated with AGEs-BSA through upregulation of the HO-1 expression in JEG-3 cells.
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Advanced glycoxylation end products, sFLt-1, Sildenafil
KMID :
1007320140200020057
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