PMID- 21277991 OWN - NLM STAT- MEDLINE DCOM- 20110801 LR - 20211203 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 43 IP - 5 DP - 2011 May TI - Mammalian Ste20-like protein kinase 3 plays a role in hypoxia-induced apoptosis of trophoblast cell line 3A-sub-E. PG - 742-50 LID - 10.1016/j.biocel.2011.01.015 [doi] AB - 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-alpha-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. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Wu, Hung-Yi AU - Wu HY AD - Department of Biological Science and Technology, National Chiao Tung University, 75 Po Ai Street, Hsinchu 300, Taiwan, ROC. FAU - Lin, Chia-Ying AU - Lin CY FAU - Chen, Tai-Chang AU - Chen TC FAU - Pan, Shien-Tung AU - Pan ST FAU - Yuan, Chiun-Jye AU - Yuan CJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110126 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - EC 1.14.13.39 (Nitric Oxide Synthase) RN - EC 1.6.3.- (NADPH Oxidases) RN - EC 2.7.1.- (STK24 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - *Apoptosis MH - Caspase 3/metabolism MH - Cell Hypoxia MH - Cell Line MH - Female MH - Humans MH - Mitogen-Activated Protein Kinase 8/metabolism MH - NADPH Oxidases/metabolism MH - Nitric Oxide Synthase/metabolism MH - Oxidative Stress MH - Placenta/cytology MH - Pregnancy MH - Protein Serine-Threonine Kinases/*metabolism MH - Signal Transduction MH - Trophoblasts/*cytology/*enzymology/metabolism MH - Up-Regulation EDAT- 2011/02/01 06:00 MHDA- 2011/08/02 06:00 CRDT- 2011/02/01 06:00 PHST- 2010/11/19 00:00 [received] PHST- 2011/01/18 00:00 [revised] PHST- 2011/01/19 00:00 [accepted] PHST- 2011/02/01 06:00 [entrez] PHST- 2011/02/01 06:00 [pubmed] PHST- 2011/08/02 06:00 [medline] AID - S1357-2725(11)00032-X [pii] AID - 10.1016/j.biocel.2011.01.015 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2011 May;43(5):742-50. doi: 10.1016/j.biocel.2011.01.015. Epub 2011 Jan 26.