title: Mammalian Ste20-like protein kinase 3 plays a role in hypoxia-induced apoptosis of trophoblast cell line 3A-sub-E.
abstract: Mammalian Ste20-like protein kinase 3 (Mst3) is a key player in inducing apoptosis in a variety of cell types and has recently been shown to participate in the signaling pathway of hypoxia-induced apoptosis of human trophoblast cell line 3A-sub-E (3A). It is believed that oxidative stress may occur during hypoxia and induce the expression of Mst3 in 3A cells via the activation of c-Jun N-terminal protein kinase 1 (JNK1). This hypothesis was demonstrated by the suppressive effect of dl-α-lipoic acid, a reactive oxygen species scavenger, in hypoxia-induced responses of 3A cells such as Mst3 expression, nitrotyrosine formation, JNK1 activation and apoptosis. Similar results were also observed in trophoblasts of human placental explants in both immunohistochemical studies and immunoblot analyses. These suggested that the activation of Mst3 might trigger the apoptotic process in trophoblasts by activating caspase 3 and possibly other apoptotic pathways. The role of nitric oxide synthase (NOS) and NADPH oxidase (NOX) in hypoxia-induced Mst3 up-regulation was also demonstrated by the inhibitory effect of N(G)-nitro-l-arginine and apocynin, which inhibits NOS and NOX, respectively. Oxidative stress was postulated to be induced by NOS and NOX in 3A cells during hypoxia. In conclusion, hypoxia induces oxidative stress in human trophoblasts by activating NOS and NOX. Subsequently, Mst3 is up-regulated and plays an important role in hypoxia-induced apoptosis of human trophoblasts.
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, 75 Po Ai Street, Hsinchu 300, Taiwan, ROC.
authors.forename: Hung-Yi
authors.initials: HY
authors.lastname: Wu
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Lin
authors.forename: Tai-Chang
authors.initials: TC
authors.lastname: Chen
authors.forename: Shien-Tung
authors.initials: ST
authors.lastname: Pan
authors.forename: Chiun-Jye
authors.initials: CJ
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D005260:Female; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D015854:Up-Regulation; D000099317:Hippo Kinases
chemical_list: D053148:Caspase 3; D048055:Mitogen-Activated Protein Kinase 8; D019255:NADPH Oxidases; D019001:Nitric Oxide Synthase; D017346:Protein Serine-Threonine Kinases; C109163:STK24 protein, human; D000099317:Hippo Kinases