Sildenafil Inhibits Advanced Glycation End Products-induced sFlt-1 Release Through Upregulation of Heme Oxygenase-1.
OBJECTIVE
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-κB 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.


CONCLUSIONS
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.
Department Obstetrics and Gynecology, Pusan National University, School of Medicine, Yangsan, Korea.
Jae Hyeok
JH
Jeong
Department Obstetrics and Gynecology, Pusan National University, School of Medicine, Yangsan, Korea.
Hwi Gon
HG
Kim
Department Obstetrics and Gynecology, Pusan National University, School of Medicine, Yangsan, Korea.
Ook Hwan
OH
Choi
Advanced glycoxylation end products; Sildenafil; sFLt-1