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Mst3 plays an important role in the hypoxia‐induced apoptosis of human trophoblasts
Author(s) -
Wu HungYi,
Lin ChiaYing,
Pan ShienTung,
Yuan ChiunJye
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.703.12
Subject(s) - apoptosis , microbiology and biotechnology , downregulation and upregulation , hypoxia (environmental) , oxidative stress , trophoblast , biology , chemistry , endocrinology , biochemistry , oxygen , placenta , gene , organic chemistry , pregnancy , fetus , genetics
Mammalian Ste20‐like protein kinase 3 (Mst3), a key player in the apoptosis of cell lines, was recently found to be highly expressed in human trophoblast in response to hypoxia. Mst3 is postulated to be activated by hypoxia and to trigger the apoptosis of human trophoblasts. In this study, this hypothesis was confirmed by the observation that hypoxia‐induced apoptosis of 3A‐sub‐E, a human trophoblast cell line, was markedly suppressed by selective knockdown of Mst3. Hypoxia was shown to induce the expression of Mst3 and the subsequent apoptotic events via the activation of nitric oxide synthase (NOS). The hypoxia‐induced Mst3 expression and the apoptosis in human trophoblasts were markedly suppressed by the inhibitor of NOS. Oxidative stress was demonstrated to be induced by NOS and to participate in the upregulation of Mst3. The hypoxia‐induced apoptosis of trophoblasts can be effectively suppressed by DL‐£\‐lipoic acid, a ROS scavenger, and apocynin, a specific inhibitor for NADPH oxidase. C‐Jun N‐terminal kinase‐1 was shown to be activated by oxidative stress and induce the upregulation of Mst3. In conclusion, Mst3 was shown to play a role in the apoptosis of placental trophoblasts in response to hypoxia. Oxidative stress was found to be elevated by hypoxia, which further induced the expression of Mst3 that triggers trophoblast apoptosis.