title: Edaravone protects against cobalt chloride-induced dysfunctions in apoptosis and invasion in trophoblast cells.
abstract: This study was performed to investigate the effects of edaravone on hypoxia-induced trophoblast cell proliferation, apoptosis, and invasion. The trophoblast cell line HTR-8 (H8) was treated with cobalt chloride (CoCl2 ) with or without a 1-hr edaravone pretreatment, followed by assessment of intracellular reactive oxygen species (ROS) levels, cell proliferation, apoptosis, migration, and invasion. Metrics of apoptosis included measurement of cysteine-aspartic acid protease 3 (CASP3) activity as well as BAX and BCL2 expression. Migration and invasion phenotypes were complemented with expression analysis of matrix metalloproteinase 2 (MMP2) and tissue inhibitor of metalloproteinase 2 (TIMP2) at the transcript and protein levels. CoCl2 inhibited the proliferation of H8 cells, promoted apoptosis, and up-regulated CASP3 activation and BAX expression while inhibiting BCL2 expression. CoCl2 treatment also reduced the invasiveness of H8 cells by inhibiting MMP2 activity. Edaravone significantly increased H8 cell proliferation; inhibited apoptosis by down-regulating CASP3 activation and BAX production while promoting BCL2 stability; and ameliorated the migration and invasion phenotypes associated with CoCl2 treatment. These results suggest that edaravone may rescue hypoxia-induced abnormalities in H8 cell proliferation, apoptosis, and invasion, thereby protecting the trophoblast lineage against hypoxia. Mol. Reprod. Dev. 83: 576-587, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: YanFang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: QingQing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: XiaoXia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: XiaoPing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
mesh_terms: D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology*; D000077553:Edaravone; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism* / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D017382:Reactive Oxygen Species; C560823:TIMP2 protein, human; D051028:bcl-2-Associated X Protein; D019716:Tissue Inhibitor of Metalloproteinase-2; D003035:Cobalt; C505407:CASP3 protein, human; D053148:Caspase 3; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C018021:cobaltous chloride; D000077553:Edaravone; D000983:Antipyrine