β-Amyloid-activated cell cycle in SH-SY5Y neuroblastoma cells
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Primary cultures of rat cortical neurons exposed to toxic concentrations of β-amyloid peptide (βAP) begin an unscheduled mitotic cell cycle that does not progress beyond the S phase. To analyze possible signal transduction pathways involved in this effect, the action of βAP has been studied in SH-SY5Y neuroblastoma cells differentiated by a 7-d exposure to 10 µM retinoic acid. Treatment with the βAP fragment, βAP(25–35), (25 µM) for 24, 48, or 72 h caused apoptotic cell death, detected by flow cytometry as a prediploid cell population. Cell cycle analysis showed that βAP(25–35) modified cell cycle profiles by markedly increasing the number of cells in the S phase and reducing the population of the G2/M area. These effects seem to involve activation of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK1/2). Inhibition of this pathway by the specific inhibitor PD98059 (2 µM) completely prevented changes of cell cycle distribution induced by βAP and significantly reduced neuronal death. The data suggest that MAPK cascade can mediate the induction of cell cycle induced by βAP, thus contributing to the toxicity of the peptide.
Index EntriesCell cycle apoptosis cyclin Alzheimer’s disease mitosis
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