title: Inhibition of BCL-2 leads to increased apoptosis and delayed neuronal differentiation in human ReNcell VM cells in vitro.
abstract: BCL-2 is a multifunctional protein involved in the regulation of apoptosis, cell cycle progression and neural developmental processes. Its function in the latter process is not well understood and needs further elucidation. Therefore, we characterized the protein expression kinetics of BCL-2 and associated regulatory proteins of the intrinsic apoptosis pathway during the process of neuronal differentiation in ReNcell VM cells with and without functional inhibition of BCL-2 by its competitive ligand HA14-1. Inhibition of BCL-2 caused a diminished BCL-2 expression and higher levels of cleaved BAX, activated Caspase-3 and cleaved PARP, all pro-apoptotic markers, when compared with untreated differentiating cells. In parallel, flow cytometric analysis of HA14-1-treated cells revealed a delayed differentiation into HuC/D+ neuronal cells when compared to untreated differentiating cells. In conclusion, BCL-2 possess a protective function in fully differentiated ReNcell VM cells. We propose that the pro-survival signaling of BCL-2 is closely connected with its stimulatory effects on neurogenesis of human neural progenitor cells.
authors.affiliation: University of Rostock, Institute of Biological Sciences, Cell Biology and Biosystems Technology, Albert-Einstein-Straße 3, D-18051 Rostock, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fröhlich
authors.affiliation: University of Rostock, Institute of Biological Sciences, Cell Biology and Biosystems Technology, Albert-Einstein-Straße 3, D-18051 Rostock, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Jaeger
authors.affiliation: University of Rostock, Institute of Biological Sciences, Cell Biology and Biosystems Technology, Albert-Einstein-Straße 3, D-18051 Rostock, Germany.
authors.forename: Dieter G
authors.initials: DG
authors.lastname: Weiss
authors.affiliation: University of Rostock, Institute of Biological Sciences, Cell Biology and Biosystems Technology, Albert-Einstein-Straße 3, D-18051 Rostock, Germany; Department of Safety and Radiation Protection, Radiation Biology Unit, Forschungszentrum Jülich GmbH, D-52425, Jülich, Germany. Electronic address: r.kriehuber@fz-juelich.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kriehuber
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D000067778:ELAV-Like Protein 3 / Q000378:metabolism; D000067779:ELAV-Like Protein 4 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001578:Benzopyrans; D000067778:ELAV-Like Protein 3; D000067779:ELAV-Like Protein 4; D004791:Enzyme Inhibitors; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate
keywords: Apoptosis; BCL-2; HA14-1; Human neural progenitor cells; Neuronal differentiation