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Okadaic Acid‐Induced Apoptosis in Neuronal Cells: Evidence for an Abortive Mitotic Attempt
Author(s) -
Nuydens Rony,
De Jong Mirjam,
Van Den Kieboom Gerd,
Heers Cara,
Dispersyn Gwenda,
Cornelissen Frans,
Nuyens Roger,
Borgers Marcel,
Geerts Hugo
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70031124.x
Subject(s) - okadaic acid , biology , mitosis , microbiology and biotechnology , cell cycle , dna fragmentation , cyclin b1 , cyclin a , fragmentation (computing) , apoptotic dna fragmentation , anisomycin , cyclin b , programmed cell death , apoptosis , cyclin dependent kinase 1 , cyclin d1 , biochemistry , phosphatase , phosphorylation , kinase , ecology
There is increasing evidence that apoptosis in postmitotic neurons is associated with a frustrated attempt to reenter the mitotic cycle. Okadaic acid, a specific protein phosphatase inhibitor, is currently used in models of Alzheimer's research to increase the degree of phosphorylation of various proteins, such as the microtubule‐associated protein tau. Okadaic acid induces programmed cell death in the human neuroblastoma cell lines TR14 and NT2‐N, as evidenced by fragmentation of DNA and attenuation of this process by protein synthesis inhibitors. In differentiated TR14 cells, okadaic acid increases the fraction of cells in the S phase, induces the appearance of cyclin B 1 and cyclin D 1 markers of the cell cycle, and triggers a time‐dependent increase in DNA fragmentation after release of a thymidine block. Fully differentiated NT2‐N cells are forced to enter the mitotic cycle as shown by DNA staining. Chromatin condensation and chromosome formation are initiated, but the cells fail to complete their mitotic cycle. These data suggest that okadaic acid forces differentiated neuronal cells into the mitotic cycle. This pattern of cyclin up‐regulation and cell cycle shift is compared with apoptosis induced by neurotrophic factor deprivation in differentiated rat pheochromocytoma PC12 cells.