Oxidative Stress Produced by Xanthine Oxidase Induces Apoptosis in Human Extravillous Trophoblast Cells

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概要

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• 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.

著者

• Wake Norio

  Department Of Gynecology And Obstetrics Kyushu University Graduate School Of Medical Sciences

• Takeda Satoru

  Department Of Cardiovascular Medicine Tohoku University Graduate School Of Medicine

• Murata Masaharu

  Department Of Advanced Medical Initiatives Faculty Of Medical Sciences Kyushu University

• Seki Hiroyuki

  Department Of Applied Chemistry Graduate School Of Engineering Kanagawa University

• Fukushima Kotaro

  Department Of Obstetrics And Gynecology Kyushu University Hospital Kyushu University

• TAKAO Tomoka

  Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

• MURATA Masaharu

  Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

• FUKUSHIMA Kotaro

  Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan

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