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KMID : 0606620080040020093
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Korean Journal of Fetal Medicine
2008 Volume.4 No. 2 p.93 ~ p.93
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Effect of hypoxia on endothelial nitric oxide synthase, NO production, intracellular survival signalling (p-ERK1/2 production, intracellular survival signalling (p-ERK1/2
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Park Mi-Hye
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Abstract
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Objective: The objective of the study was to evaluate the effects of hypoxia on eNOS, activation of intracellular survival signalling (p-ERK and p-AKT) and apoptosis in human term trophoblast
Study Design: Human term trophoblasts were isolated from term placentas of uncomplicated human pregnancies.
Cytokeratin staining comfirmed cytotrophoblast (CT) cell type. CT cells were cultured in either 21% oxygen (control
condition) or 2% oxygen (Hypoxia condition) for 24, 48, and 72 hours. At each time point eNOS, p-NOS (Ser1177), p-ERK
and p-AKT protein were assessed by Western blot and apoptosis by dUTP nick end-labelling (TUNEL) assay. Media was
collected for NOx determination at each time point.
Results:
Compared with control condition, CT cells exposed to hypoxia showed :
(1) decreased eNOS expression at 48hours (p<.002) and 72hours (p<.02);
(2) increased p-eNOS (Ser1177) expression at at 48hours (p<.003) and 72hours (p=0.074)
(3) no difference in the total NOx production ;
(4) increased p-ERK expression at 24 hours 48hours and 72 hours (p<0.02. p<0.04 and p<0.04, respectively);
(5) increased p-AKT expression at 24hours (p<0.05) and
(6) increased apoptosis at 48hours (p<0.02) and 72hours (p=0.079) ;
Conclusion:
These results suggest that hypoxia decreases eNOS expression but increases phospho-eNOS (Ser1177) expression in
cultured human trophoblast and hypoxia increases activation of intracellular survival signalling expression in cultured human CT and hypoxia induced apoptosis is associated with insufficient activation of AKT.
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KEYWORD
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