Sildenafil Inhibits Advanced Glycation End Products-induced sFlt-1 Release Through Upregulation of Heme Oxygenase-1.
- Author:
Jae Hyeok JEONG
1
;
Hwi Gon KIM
;
Ook Hwan CHOI
Author Information
- Publication Type:Original Article
- Keywords: Advanced glycoxylation end products; sFLt-1; Sildenafil
- MeSH: Bilirubin; Choriocarcinoma; Citric Acid; Cobalt; Enzyme-Linked Immunosorbent Assay; Female; Glycosylation End Products, Advanced; Heme Oxygenase-1*; NF-kappa B; Pregnancy; Reactive Oxygen Species; RNA, Messenger; RNA, Small Interfering; Serum Albumin, Bovine; Up-Regulation*; Vascular Endothelial Growth Factor Receptor-1; Zinc; Sildenafil Citrate
- From:Journal of Menopausal Medicine 2014;20(2):57-68
- CountryRepublic of Korea
- Language:English
- 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-kappaB 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.
