The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells |
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Authors: | Yang Se-Ran Cho Sung-Dae Ahn Nam-Shik Jung Ji-Won Park Joon-Suk Jo Eun-Hye Hwang Jae-Woong Kim Sung-Hoon Lee Bong-Hee Kang Kyung-Sun Lee Yong-Soon |
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Institution: | aLaboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea bOriental Medical College of Natural Science, Kyunghee University, Suwon, Republic of Korea cDepartment of Anatomy and Neurobiology, College of Medicine, Cheju National University, Cheju, Republic of Korea |
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Abstract: | The two distinct members of the mitogen-activated protein (MAP) kinase family c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, play an important role in central nervous system (CNS) development and differentiation. However, their role and functions are not completely understood in CNS. To facilitate in vitro study, we have established an immortal stem cell line using SV40 from fetal rat embryonic day 17. In these cells, MAP kinase inhibitors (SP600125, SB202190, and PD98059) were treated for 1, 24, 48, and 72 h to examine the roles of protein kinases. Early inhibition of JNK did not alter phenotypic or morphological changes of immortalized cells, however overexpression of Bax and decrease of phosphorylated AKT was observed. The prolonged inhibition of JNK induced polyploidization of immortalized cells, and resulted in differentiation and inhibition of cell proliferation. Moreover, JNK and p38 MAP kinase but not ERK1/2 was activated, and p21, p53, and Bax were overexpressed by prolonged inhibition of JNK. These results indicate that JNK and p38 MAP kinase could play dual roles on cell survival and apoptosis. Furthermore, this established cell line could facilitate study of the role of JNK and p38 MAP kinase on CNS development or differentiation/apoptosis. |
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Keywords: | Neural stem cells c-Jun N-terminal protein kinase p38 MAP kinase Extracellular regulated kinase 1/2 Immortalization Simian virus 40 (SV40) large |
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