Oxidative Stress Produced by Xanthine Oxidase Induces Apoptosis in Human
Extravillous Trophoblast Cells |
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Authors: | Masaharu MURATA Kotaro FUKUSHIMA Tomoka TAKAO Hiroyuki SEKI Satoru TAKEDA Norio WAKE |
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Institution: | 1) Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan;2) Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, Saitama 350-8550, Japan;3) Department of Obstetrics and Gynecology, Juntendo University, Tokyo 113-8421, Japan |
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Abstract: | Oxidative stress has been recognized as an important factor in the pathophysiology of
preeclampsia. It has been reported that the expression of xanthine oxidase (XO) in the
cytotrophoblast and plasma hydrogen peroxide (H2O2) level are
significantly higher in preeclamptics than in control women. The aim of this study was to
clarify the biological influence of reactive oxygen species (ROS) produced by XO on
extravillous trophoblast (EVT) cells. TCL1 cells, a human immortalized EVT cell line, were
incubated with xanthine and XO (X/XO). We then measured the cell number, urate level of
the culture media and the apoptotic cell ratio. Similar experiments were performed with
additional administration of allopurinol, catalase, L-NAME or D-NAME, and with
administration of H2O2 in substitution for X/XO. We assessed the
effects of H2O2 on invasion ability, tube-like formation and protein
expression of HIF1A and ITGAV of TCL1. Finally, the apoptotic cell ratio using primary
cultured trophoblasts was measured following exposure to H2O2. X/XO
decreased the relative cell number and increased the urate level and apoptotic cell ratio
significantly. Elevation of the urate level and apoptotic cell ratio was attenuated by
allopurinol and catalase, respectively. L-NAME and D-NAME had no influence on these
effects. H2O2 also decreased the relative cell number. Pretreatment
with H2O2 significantly inhibited the invasion ability, tube-like
formation and HIF1A and ITGAV of TCL1. H2O2 also induced apoptosis
in primary cultured trophoblasts. In conclusion, ROS produced by XO induced apoptosis and
affected EVT function including invasion and differentiation. |
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Keywords: | Apoptosis Extravillous trophoblast Oxidative stress Xanthine oxidase |
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