title: Expression of cell cycle-related genes during neuronal apoptosis: is there a distinct pattern?
abstract: An emerging hypothesis considers the process of neuronal apoptosis as a consequence of unscheduled and unsynchronized induction of cell cycle mediators. Induction of several cell cycle genes precedes neuronal apoptosis and may be involved in determination of cell fate. We have now characterized changes in expression of cell cycle genes during apoptosis induced by oxidative stress in chick post-mitotic sympathetic neurons. Induction of cyclin B occurred prior to the commitment of neurons to both dopamine- and peroxide-triggered apoptosis. Both the neuronal death and the rise in cyclin B were inhibited by antioxidant treatment, suggesting a functional role for cyclin B induction during neuronal apoptosis. Induction of the cyclin dependent kinase CDK5 protein coincided with the time point when neurons were irreversibly committed to die. Expression of other cell cycle mediators such as cyclin D1 and the cyclin dependent kinases CDC2 and CDK2 was undetected and not induced by exposure to oxidative stress. Comparative analysis of the profile of cell cycle mediators induced during neuronal apoptosis of different neuronal cell populations revealed no distinct pattern of events. There are no cell cycle stage-specific mediators that are ultimately stimulated during neuronal apoptosis, suggesting that multiple pathways of re-activating the dormant cell-cycle, converge to determine entry into apoptosis. Nevertheless, the existence of some cell cycle mediators, that were not reported so far to be induced in post mitotic neurons during oxidative stress, substantiate them as part of the strong differentiating forces.
authors.affiliation: Department of Neurology and Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Shirvan
authors.forename: I
authors.initials: I
authors.lastname: Ziv
authors.forename: R
authors.initials: R
authors.lastname: Zilkha-Falb
authors.forename: T
authors.initials: T
authors.lastname: Machlyn
authors.forename: A
authors.initials: A
authors.lastname: Barzilai
authors.forename: E
authors.initials: E
authors.lastname: Melamed
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002478:Cells, Cultured; D002642:Chick Embryo; D019926:Cyclin B / Q000096:biosynthesis; D051357:Cyclin-Dependent Kinase 2; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D004229:Dithiothreitol / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000166:cytology* / Q000502:physiology*; D005786:Gene Expression Regulation; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D019926:Cyclin B; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D051360:Cyclin-Dependent Kinase 5; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D004229:Dithiothreitol; D004298:Dopamine