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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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To examine the effect of diazoxide on hypoxia-induced soluble fms-like tyrosin kinase-1 (sFlt-1) release in JEG-3 choriocarcinoma cells.Methods: Cells were cultured under normoxia (20% O2) or hypoxia (1% O2), and expression of sFlt-1 mRNA and protein release was determined by quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) assays and enzyme-linked immunosorbent assay (ELISA). Results: Tumor necrosis factor-alpha (TNF-α) as well as hypoxia stimulated sFlt-1 release and diazoxide inhibited both of them. The selective inhibitor of mitochondrial adenosine triphosphat (ATP)-sensitive K+ channel opener (KATP) 5-hydroxydecanoate (5-HD) completely reversed the diazoxide-induced inhibition of hypoxia-stimulated sFlt-1 release. qRT-PCR and Western blot analyses showed that diazoxide up-regulated the heme oxygenase-1 (HO-1) expression. In addition, the HO-1 inducer cobalt protoporphyrin (CoPP) and the metabolic product of HO-1 bilirubin mimicked diazoxide to inhibit sFlt-1 release and reactive oxygen species (ROS) production under hypoxia, whereas the HO-1 inhibitor zinc protoporphyrin IX (ZnPP IX) antagonized the effect of diazoxide. In cells transfected with the HO-1 siRNA, diazoxide did not exert any effect on sFlt-1 release and ROS production under hypoxia.Conclusion: These results, taken together, strongly suggest that up-regulation of the HO-1 expression is the crucial mechanism responsible for the diazoxide-induced inhibition of the sFlt-1 release and ROS production under hypoxia. (J Menopausal Med 2014;20:21-31)
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참고문헌 (23)
참고문헌 신청
Ahmad S / 2001 / Regulation of soluble VEGFR-1 by VEGF and oxygen and its elevation in pre-eclampsia and fetal growth restriction / Placenta 22 : 7 ~
Ahmad S / 2004 / Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia / Circ Res 95 : 884 ~ 891
Ahmed A / 1995 / Whittle MJ, Rushton DI, Rollason T. Colocalisation of vascular endothelial growth factor and its Flt-1 receptor in human placenta / Growth Factors 12 : 235 ~
Anthony FW / 1997 / Variation in detection of VEGF in maternal serum by immunoassay and the possible influence of binding proteins / Ann Clin Biochem 34 : 276 ~ 280
Bergmann A / 2010 / Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model / Cell Mol Med 14 : 1857 ~ 1867
Ahmad S / 2004 / Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia / Circ Res 95 : 884 ~ 891
Ahmed A / 1995 / Whittle MJ, Rushton DI, Rollason T. Colocalisation of vascular endothelial growth factor and its Flt-1 receptor in human placenta / Growth Factors 12 : 235 ~
Anthony FW / 1997 / Variation in detection of VEGF in maternal serum by immunoassay and the possible influence of binding proteins / Ann Clin Biochem 34 : 276 ~ 280
Bergmann A / 2010 / Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model / Cell Mol Med 14 : 1857 ~ 1867
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