title: Amyloid precursor protein is involved in staurosporine induced glial differentiation of neural progenitor cells.
abstract: Staurosporine (STS) has been reported as not only a pro-apoptotic agent, but also a terminal differentiation inducer in several neuroblastoma cell lines. Here, we report involvement of amyloid precursor protein (APP) in a STS induced astrocytic differentiation of human neural progenitor cells (NT-2/D1). We found that STS-treated NT-2/D1 cells expressed astrocyte-specific glial fibrillary acidic protein (GFAP), aspartate transporter, and glutamate transporter-1 with a distinctive astrocytic morphology. STS treatment increased GFAP promoter activity and increased expression and secretion of APP in NT-2/D1 cell culture. Overexpressed APP enhanced GFAP promoter activity and expression of GFAP, while gene silencing of APP by RNA interference decreased GFAP expression. These results indicate involvement of APP in STS induced astrocytic differentiation of NT-2/D1 cells. Furthermore, suppression of ERK1/2 phosphorylation, which is known to regulate APP expression by a MEK1 inhibitor, PD098059, reduced both APP and GFAP expression in STS treated NT-2/D1 cells. Thus, STS may induce astrocytic differentiation of NT-2/D1 by increasing APP levels associate with activation of ERK pathway.
authors.affiliation: Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816, USA.
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Kwak
authors.forename: Elena
authors.initials: E
authors.lastname: Choumkina
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Sugaya
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors; D034622:RNA Interference; D019311:Staurosporine / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
chemical_list: D016564:Amyloid beta-Protein Precursor; D027341:Excitatory Amino Acid Transporter 1; D005419:Flavonoids; D005904:Glial Fibrillary Acidic Protein; D047428:Protein Kinase Inhibitors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1; D019311:Staurosporine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one