title: [Inhibition of Bcl-2 stimulates neuronal stem proliferation in organotypic cultures of mice hippocampus].
abstract: In the current study, we investigated the participation of Bcl-2 in both processes of hippocampus neuronal stem cells (NSC) proliferation and differentiation. Present experiments are performed on organotypic cultures of mice hippocampus. A selective inhibitor Bcl-2 HA14-1 (10 μM) is supplied in incubating medium and the concentration is maintained at a constant level. Our data demonstrate that per cent of surviving cells is significantly higher in the group with the supplement HA14-1 then in the control group. In additional, expressions both phospho-histone H3 and Oct3/4 significantly increase in the group with supplement HA14-1. The facts suggest about activation of NSCs proliferation. After 6 weeks incubation, formation of embryoid bodies is observed in the group with HA14-1, that also suggest about NSCs proliferation, but not their differentiation. Also we estimate the level of NSCs differentiation. Our data have shown that the level of CRMP-2 (a protein which participates in axon growth during NSCs differentiation) decreases in the group with HA14-1. We also estimate level of ERK1/2 kinase activity of the MAPK signaling pathway, which immediately regulates neuronal differentiation. Decreasing of both activities ERK1/2 and CRMP-2 indicates diminution of neuronal differentiation in the experimental group. Thus, we demonstrate that inhibition of Bcl-2 increasingly stimulates NSCs proliferation, so that, it suggests that Bcl-2 controls NSCs differentiation to neurons.
authors.forename: Ia S
authors.initials: IaS
authors.lastname: Beliaeva
authors.forename: L S
authors.initials: LS
authors.lastname: Nikitina
authors.forename: E V
authors.initials: EV
authors.lastname: Chernigovskaia
authors.forename: M V
authors.initials: MV
authors.lastname: Glazova
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D009570:Nitriles / Q000008:administration & dosage; D009924:Organ Culture Techniques; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate