PMID- 17275903
OWN - NLM
STAT- MEDLINE
DCOM- 20160423
LR  - 20181201
IS  - 0143-4004 (Print)
IS  - 0143-4004 (Linking)
VI  - 28
IP  - 8-9
DP  - 2007 Aug-Sep
TI  - Hypoxia and lactate production in trophoblast cells.
PG  - 854-60
AB  - The etiology of preeclampsia is unknown but is thought to be related to hypoxia 
      in the placenta. We previously reported that the enzyme lactate dehydrogenase 
      (LDH) has increased activity and gene expression in placentas from preeclamptic 
      pregnancies [Tsoi SCM, Zheng J, Xu F, Kay HH. Differential expression of lactate 
      dehydrogenase isozymes (LDH) in human placenta with high expression of LDH-A(4) 
      isozyme in the endothelial cells of pre-eclampsia villi. Placenta 
      2001;22:317-22]. LDH is responsible for pyruvate conversion to lactate through 
      glycolysis. In this study, we further investigated the role of hypoxia in primary 
      trophoblast cells and a cultured cell line, JEG3 cells, to obtain a better 
      understanding of how it affects the activities of lactate dehydrogenase, lactate 
      production and regulatory genes, as a possible model for preeclampsia. Primary 
      trophoblast cells and JEG3 cells were cultured under 1% oxygen. At 6, 12 and 24h, 
      cells were analyzed for LDHA and LDHB isozyme activities, mRNA and protein 
      expression compared to standard culture conditions. Lactate was measured from 
      cell medium. The hypoxia inducible transcription factor (HIF-1alpha) protein 
      expression was confirmed by western blot. Two lactate transporters (MCT1 and 
      MCT4) mRNA and protein expression were also studied under hypoxia. Finally, 
      lactate was measured in plasma obtained from patients with severe preeclampsia. 
      Under hypoxic conditions, LDHA mRNA is increased in primary trophoblast cells and 
      JEG3 cells. The HIF-1alpha protein expression is higher in hypoxia-treated JEG3 
      cells than control. LDHA isozyme activity and its protein expression are 
      increased most significantly at 24h of culture under hypoxia. However, LDHB 
      protein is unchanged while its mRNA is decreased. Lactate secretion from JEG3 
      cells under hypoxia is increased, as is the lactate levels in the plasma from 
      preeclampsia patients. Of the two lactate transporters studied, MCT4 mRNA and 
      protein level are increased under hypoxia. Our findings support the role of 
      hypoxia in inducing HIF-1alpha activity in trophoblasts and increasing LDH 
      transcription as well as its activity. Higher levels of lactate are produced and 
      secreted which may contribute to the higher lactate levels in plasma of 
      preeclamptic patients. These mechanisms may be important in the pathophysiology 
      of preeclampsia.
FAU - Kay, H H
AU  - Kay HH
AD  - Department of Obstetrics and Gynecology, College of Medicine, University of 
      Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, 
      USA. hhkay@uams.edu
FAU - Zhu, S
AU  - Zhu S
FAU - Tsoi, S
AU  - Tsoi S
LA  - eng
PT  - Journal Article
DEP - 20070202
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 33X04XA5AT (Lactic Acid)
SB  - IM
MH  - Cell Line, Tumor
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - *Lactic Acid
MH  - Placenta/metabolism
MH  - Pre-Eclampsia/metabolism
MH  - *Trophoblasts/metabolism
EDAT- 2007/02/06 09:00
MHDA- 2016/04/24 06:00
CRDT- 2007/02/06 09:00
PHST- 2006/10/03 00:00 [received]
PHST- 2006/11/14 00:00 [revised]
PHST- 2006/11/15 00:00 [accepted]
PHST- 2007/02/06 09:00 [pubmed]
PHST- 2016/04/24 06:00 [medline]
PHST- 2007/02/06 09:00 [entrez]
AID - S0143-4004(06)00291-8 [pii]
AID - 10.1016/j.placenta.2006.11.011 [doi]
PST - ppublish
SO  - Placenta. 2007 Aug-Sep;28(8-9):854-60. doi: 10.1016/j.placenta.2006.11.011. Epub 
      2007 Feb 2.