Inhibition of BCL‐2 leads to increased apoptosis and delayed neuronal differentiation in human ReNcell VM cellsin vitro
| Autor: | Alexandra Jaeger, Michael Fröhlich, Ralf Kriehuber, Dieter G. Weiss |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Time Factors Poly ADP ribose polymerase Apoptosis ELAV-Like Protein 3 ELAV-Like Protein 4 Biology 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Nitriles Humans Benzopyrans Enzyme Inhibitors Cell Line Transformed bcl-2-Associated X Protein Neurons Neurogenesis Intrinsic apoptosis Cell Differentiation Flow Cytometry Ligand (biochemistry) Neural stem cell In vitro Cell biology 030104 developmental biology Gene Expression Regulation Proto-Oncogene Proteins c-bcl-2 Mitochondrial Membranes Immunology 030217 neurology & neurosurgery Function (biology) Developmental Biology |
| Zdroj: | International Journal of Developmental Neuroscience. 48:9-17 |
| ISSN: | 1873-474X 0736-5748 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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