title: [The role of p53 in the regulation of proliferation and differentiation of the neural progenitors in mouse hippocampal organotypic culture].
abstract: In the present work we have studied the effects of p53 on the proliferation and differentiation of neural progenitor cells (NPC) in mouse hippocampal organotypic culture. To study the role of p53 the selective p53 inhibitor pifithrin-alpha (PFT) and activator tenovin 1 (TEN) were used in the experiments. Obtained data demonstrated that the injections of PFT did not affect on the amount of phospho-H3 positive cells in the subgranular zone of hippocampus. This data revealed that p53 inhibition does not change the proliferation level of the NPC. In opposite, at the TEN treatments we observed increased of the proliferation activity. Analysis of Pim-1 and Phb 1, which regulate cell cycle progression, demonstrated that p53 activation led to increased level of Pim-1 as well as the proliferation. Thus, our data correlate with published ones and proposed that Pim-1 positively regulates NPC cell cycle progression. In opposite to Pim-1, Phb 1 has anti-proliferative action. Our obtained data demonstrated that TEN diminished Phb 1 expression. Primarily PFT injections led to the increasing Phbl level, but then dramatically decreased it that accompanied with unchanged proliferation level. In other words, increased proliferation level after TEN treatments, which we observed, can be partly depend from the inhibition of anti-proliferative activity of Phb. In our study we demonstrated that both TEN and in a greater degree PFT stimulates neuronal differentiation by activation of CRMP-2 expression, but do not affect on gliogenesis. Thus, obtained data revealed that p53 is an important factor of neuronal differentiation and, probably, p53 action is mediated by cell cycle regulator protein such as Pim-1 and Phbl.
authors.forename: Yu S
authors.initials: YS
authors.lastname: Grigoreva
authors.forename: M V
authors.initials: MV
authors.lastname: Glazova
mesh_terms: D000083:Acetanilides / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D052160:Benzothiazoles / Q000494:pharmacology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D055495:Neurogenesis; D000091402:Prohibitins; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000083:Acetanilides; D000970:Antineoplastic Agents; D052160:Benzothiazoles; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000091402:Prohibitins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; C095114:collapsin response mediator protein-2; D014050:Toluene; C000594735:tenovin-1; C121565:pifithrin; C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1; D013890:Thiourea