title: Sequential expression patterns of apoptosis- and cell cycle-related proteins in neuronal response to severe or mild transient hypoxia.
abstract: Severe hypoxia was shown to induce apoptotic death in developing brain neurons, whereas mild hypoxia was demonstrated to stimulate neurogenesis. Since the apoptotic process may share common pathways with mitosis, expression profiles of proteins involved in apoptosis or the cell cycle were analyzed by immunohistochemistry and/or western blotting, in relation with cell outcome of cultured neurons from fetal rat forebrain subjected to either lethal (6 h) or non-lethal (3 h) hypoxia (95% N(2)/5% CO(2)). Hypoxia for 6 h led to apoptosis that was inhibited by the cell cycle blocker olomoucine. Transient overexpression of proliferating cell nuclear antigen was followed by increasing expression of p53, p21, Bax and caspases, whereas Bcl-2 and heat shock proteins were progressively repressed. Conversely, a 3-h hypoxic insult initiated neuronal mitosis, with increased thymidine incorporation. In these conditions, levels of proliferating cell nuclear antigen, Rb, Bcl-2 and heat shock proteins were persistently elevated, while expression of p53, p21, Bax and caspases gradually decreased. These data confirm that hypoxia promotes cell cycle activation, whatever the stress intensity. This process is then aborted following apoptosis-inducing hypoxia, whereas sublethal insult would trigger neurogenesis, at least in developing brain neurons in vitro, by stimulating timed expression of neurogenic and survival-associated proteins.
authors.affiliation: Adaptation Néonatale and Développement (JE 2164), Université Henri Poincaré, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Bossenmeyer-Pourié
authors.forename: V
authors.initials: V
authors.lastname: Lièvre
authors.forename: S
authors.initials: S
authors.lastname: Grojean
authors.forename: V
authors.initials: V
authors.lastname: Koziel
authors.forename: T
authors.initials: T
authors.lastname: Pillot
authors.forename: J L
authors.initials: JL
authors.lastname: Daval
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D053938:DNA Fragmentation / Q000502:physiology*; D005260:Female; D005333:Fetus; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; C493958:Cdkn1a protein, rat; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018840:HSP70 Heat-Shock Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D020170:Caspase 1