title: The role of p38 MAP kinase and c-Jun N-terminal protein kinase signaling in the differentiation and apoptosis of immortalized neural stem cells.
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.
authors.affiliation: Laboratory of Stem Cell and Tumor Biology, Department of Veterinary Public Health, College of Veterinary Medicine, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Se-Ran
authors.initials: SR
authors.lastname: Yang
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Nam-Shik
authors.initials: NS
authors.lastname: Ahn
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Jung
authors.forename: Joon-Suk
authors.initials: JS
authors.lastname: Park
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Jo
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Hwang
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Bong-Hee
authors.initials: BH
authors.lastname: Lee
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Yong-Soon
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002461:Cell Line, Transformed; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one