caa a22 4500 606234950 CHVBK 20210128101240.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s11010-014-2208-y doi (NATIONALLICENCE)springer-10.1007/s11010-014-2208-y Ouabain elicits human glioblastoma cells apoptosis by generating reactive oxygen species in ERK-p66SHC-dependent pathway [Elektronische Daten] [Xiaofei Yan, FenLi Liang, Dongmin Li, Jin Zheng] Excessive reactive oxygen species (ROS) generation has been implicated as one of main agents in ouabain-induced anticancer effect. Unfortunately, the signaling pathways under it are not very clarified. In the present study, we investigated the molecular mechanism involved in ouabain-induced ROS generation and cell apoptosis on human U373MG and U87MG glioma cells. Ouabain-induced glioblastoma cells apoptosis and increased ROS generation. Clearance ROS by three different ROS scavenger partly, but not totally, reversed ouabain's effect on cell apoptosis. Ouabain-induced ROS generation was not regulated by calcium overload, reduced nicotinamide adenine dinucleotide phosphate oxidation, but by p66Shc phosphorylation. Ouabain treatment increased p66Shc Ser36 phosphorylation. Knockdown of p66Shc by siRNA significantly inhibited ROS generations in response to ouabain. Ouabain-induced p66Shc phosphorylation through Src/Ras/extracellular signal-regulated kinase signal pathway. Our results uncovered a novel signaling pathway with p66Shc, ouabain-induced ROS generation, and glioblastoma cell apoptosis. Springer Science+Business Media New York, 2014 Glioblastoma nationallicence Ouabain nationallicence ROS nationallicence p66Shc nationallicence Na+/K+-ATPase nationallicence Yan Xiaofei Department of Biochemistry and Molecular Biology, Medical School, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut Liang FenLi Center for Cancer Research, Medical School, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut Li Dongmin Department of Biochemistry and Molecular Biology, Medical School, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut Zheng Jin First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 95-104 0300-8177 398:1-2<95 2015 398 11010 https://doi.org/10.1007/s11010-014-2208-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2208-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yan Xiaofei Department of Biochemistry and Molecular Biology, Medical School, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut NATIONALLICENCE 700 1- Liang FenLi Center for Cancer Research, Medical School, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut NATIONALLICENCE 700 1- Li Dongmin Department of Biochemistry and Molecular Biology, Medical School, Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut NATIONALLICENCE 700 1- Zheng Jin First Affiliated Hospital of Medical College of Xi'an Jiaotong University, 710061, Xi'an, Shaanxi, People's Republic of China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 398/1-2(2015-01-01), 95-104 0300-8177 398:1-2<95 2015 398 11010