PMID- 15598682
OWN - NLM
STAT- MEDLINE
DCOM- 20050412
LR  - 20161124
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 90
IP  - 3
DP  - 2005 Mar
TI  - Hypoxia up-regulates hypoxia-inducible factor-1alpha expression through RhoA 
      activation in trophoblast cells.
PG  - 1712-9
AB  - During early pregnancy, trophoblast cells are exposed to relatively low-oxygen 
      tension. Recently, the Rho GTPase family has been shown to play a key role in 
      hypoxia-inducible factor-1 (HIF-1) alpha induction in renal cell carcinoma. The 
      present study was designed to investigate the effect of low-oxygen conditions on 
      RhoA expression in trophoblast cells isolated from early stages of human placenta 
      and in trophoblast-derived BeWo cells and JAR cells. Immunoblot and RT-PCR 
      analyses showed that low-oxygen conditions (1% O(2) or 250 mum CoCl(2)) 
      stimulated expression of RhoA protein and mRNA. Pull-down assays demonstrated 
      that these low-oxygen conditions increased RhoA activity. Preincubation of BeWo 
      cells with Clostridium botulinum C3 exoenzyme, a specific inhibitor of Rho, 
      inhibited hypoxia-induced HIF-1alpha expression. Under 1% O(2) or 250 mum 
      CoCl(2), BeWo cells, transfected with a dominant-negative RhoA, exhibited 
      decreased levels of HIF-1alpha protein and mRNA compared with the control vector 
      transfectants. BeWo cells expressing constitutively active RhoA showed enhanced 
      protein levels of not only HIF-1alpha but also vascular endothelial growth factor 
      (VEGF) and glucose transporter 1, which are target gene products of HIF-1alpha. 
      These findings suggest that up-regulation of RhoA induced by low-oxygen 
      conditions may play an important role in regulation of HIF-1alpha expression in 
      trophoblast cells.
FAU - Hayashi, Masami
AU  - Hayashi M
AD  - Department of Obstetrics and Gynecology, Osaka University, Faculty of Medicine, 
      2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
FAU - Sakata, Masahiro
AU  - Sakata M
FAU - Takeda, Takashi
AU  - Takeda T
FAU - Tahara, Masahiro
AU  - Tahara M
FAU - Yamamoto, Toshiya
AU  - Yamamoto T
FAU - Minekawa, Ryoko
AU  - Minekawa R
FAU - Isobe, Aki
AU  - Isobe A
FAU - Tasaka, Keiichi
AU  - Tasaka K
FAU - Murata, Yuji
AU  - Murata Y
LA  - eng
PT  - Journal Article
DEP - 20041214
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Glucose Transporter Type 1)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Monosaccharide Transport Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (SLC2A1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.4.2.- (ADP Ribose Transferases)
RN  - EC 2.4.2.- (exoenzyme C3, Clostridium botulinum)
RN  - EC 3.4.24.69 (Botulinum Toxins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - ADP Ribose Transferases/pharmacology
MH  - Botulinum Toxins/pharmacology
MH  - Cells, Cultured
MH  - Female
MH  - Gene Expression/physiology
MH  - Glucose Transporter Type 1
MH  - Humans
MH  - Hypoxia/metabolism/*physiopathology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Monosaccharide Transport Proteins/genetics
MH  - Oxygen/pharmacology
MH  - Pregnancy
MH  - RNA, Messenger/analysis
MH  - Transcription Factors/*genetics/metabolism
MH  - Trophoblasts/cytology/drug effects/*physiology
MH  - Vascular Endothelial Growth Factor A/genetics
MH  - rhoA GTP-Binding Protein/antagonists & inhibitors/*metabolism
EDAT- 2004/12/16 09:00
MHDA- 2005/04/13 09:00
CRDT- 2004/12/16 09:00
PHST- 2004/12/16 09:00 [pubmed]
PHST- 2005/04/13 09:00 [medline]
PHST- 2004/12/16 09:00 [entrez]
AID - jc.2004-1547 [pii]
AID - 10.1210/jc.2004-1547 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2005 Mar;90(3):1712-9. doi: 10.1210/jc.2004-1547. Epub 
      2004 Dec 14.