title: Oxidative stress produced by xanthine oxidase induces apoptosis in human extravillous trophoblast cells.
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 (H(2)O(2)) 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 H(2)O(2) in substitution for X/XO. We assessed the effects of H(2)O(2) 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 H(2)O(2). 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. H(2)O(2) also decreased the relative cell number. Pretreatment with H(2)O(2) significantly inhibited the invasion ability, tube-like formation and HIF1A and ITGAV of TCL1. H(2)O(2) also induced apoptosis in primary cultured trophoblasts. In conclusion, ROS produced by XO induced apoptosis and affected EVT function including invasion and differentiation.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Murata
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fukushima
authors.forename: Tomoka
authors.initials: T
authors.lastname: Takao
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.forename: Satoru
authors.initials: S
authors.lastname: Takeda
authors.forename: Norio
authors.initials: N
authors.lastname: Wake
mesh_terms: D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018384:Oxidative Stress; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D014527:Uric Acid; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D019331:NG-Nitroarginine Methyl Ester