PMID- 25371888
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141105
LR  - 20211021
IS  - 2288-6478 (Print)
IS  - 2288-6761 (Electronic)
IS  - 2288-6478 (Linking)
VI  - 20
IP  - 1
DP  - 2014 Apr
TI  - Mitochondrial Channel Opener Diazoxide Attenuates Hypoxia-Induced sFlt-1 Release 
      in Human Choriocarcinoma Cells.
PG  - 21-31
LID - 10.6118/jmm.2014.20.1.21 [doi]
AB  - OBJECTIVES: 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-alpha) 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.
FAU - Shin, Byeong Seop
AU  - Shin BS
AD  - Department of Obstetrics and Gynecology, Pusan National University School of 
      Medicine, Busan, Korea.
FAU - Kim, Hwi Gon
AU  - Kim HG
AD  - Department of Obstetrics and Gynecology, Pusan National University School of 
      Medicine, Busan, Korea.
FAU - Choi, Ook Hwan
AU  - Choi OH
AD  - Department of Obstetrics and Gynecology, Pusan National University School of 
      Medicine, Busan, Korea.
LA  - eng
PT  - Journal Article
DEP - 20140428
PL  - Korea (South)
TA  - J Menopausal Med
JT  - Journal of menopausal medicine
JID - 101632648
PMC - PMC4217563
OTO - NOTNLM
OT  - Diazoxide
OT  - Heme oxygenase-1
OT  - Reactive oxygen speciese
OT  - Vascular endothelial growth factor receptor-1
EDAT- 2014/11/06 06:00
MHDA- 2014/11/06 06:01
PMCR- 2014/04/01
CRDT- 2014/11/06 06:00
PHST- 2014/02/25 00:00 [received]
PHST- 2014/03/07 00:00 [revised]
PHST- 2014/03/07 00:00 [accepted]
PHST- 2014/11/06 06:00 [entrez]
PHST- 2014/11/06 06:00 [pubmed]
PHST- 2014/11/06 06:01 [medline]
PHST- 2014/04/01 00:00 [pmc-release]
AID - 10.6118/jmm.2014.20.1.21 [doi]
PST - ppublish
SO  - J Menopausal Med. 2014 Apr;20(1):21-31. doi: 10.6118/jmm.2014.20.1.21. Epub 2014 
      Apr 28.