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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Preferential Fas-mediated apoptotic execution at G1 phase: the resistance of mitotic cells to the cell death
T Hashimoto1, K Juso, M Nakano
1Biosignal Research Center, Kobe University, Kobe, Japan.
Abstract:
Apoptosis is induced by various stresses generated from the extracellular and intracellular environments. The fidelity of the cell cycle is monitored by surveillance mechanisms that arrest its further progression if any crucial process has not been completed or damages are sustained, and then the cells with problems undergo apoptosis. Although the molecular mechanisms involved in the regulation of the cell cycle and that of apoptosis have been elucidated, the links between them are not clear, especially that between cell cycle and death receptor-mediated apoptosis. By using the HeLa.S-Fucci (fluorescent ubiquitination-based cell cycle indicator) cells, we investigated the relationship between the cell cycle progression and apoptotic execution. To monitor apoptotic execution during cell cycle progression, we observed the cells after induction of apoptosis with time-lapse fluorescent microscopy. About 70% of Fas-mediated apoptotic cells were present at G(1) phase and about 20% of cells died immediately after cytokinesis, whereas more than 60% of etoposide-induced apoptotic cells were at S/G(2) phases in random culture of the cells. These results were confirmed by using synchronized culture of the cells. Furthermore, mitotic cells showed the resistance to Fas-mediated apoptosis. In conclusion, these findings suggest that apoptotic execution is dependent on cell cycle phase and Fas-mediated apoptosis preferentially occurs at G(1) phase.
Insights
Cell cycle phase dictates apoptosis execution. Fas-mediated apoptosis primarily occurs in the G1 phase, while etoposide-induced apoptosis targets S/G2 phases, revealing distinct cell death pathway dependencies.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis (programmed cell death) is crucial for development and tissue homeostasis.
- Cell cycle surveillance mechanisms ensure genomic integrity and trigger apoptosis upon damage.
- The precise relationship between cell cycle progression and apoptosis, particularly death receptor-mediated pathways, remains incompletely understood.
Purpose of the Study:
- To investigate the cell cycle phase-specific execution of apoptosis.
- To elucidate the relationship between cell cycle progression and Fas-mediated apoptosis.
- To compare cell cycle dependency in Fas-mediated versus etoposide-induced apoptosis.
Main Methods:
- Utilized HeLa.S-Fucci cells for real-time cell cycle monitoring.
- Employed time-lapse fluorescent microscopy to observe apoptotic execution.
- Investigated apoptosis in both random and synchronized cell cultures.
- Induced apoptosis using Fas-mediated and etoposide treatments.
Main Results:
- Fas-mediated apoptosis predominantly occurred in the G1 phase (approx. 70%).
- Approximately 20% of cells undergoing Fas-mediated apoptosis died post-cytokinesis.
- Etoposide-induced apoptosis was significantly higher in the S/G2 phases (over 60%).
- Mitotic cells exhibited resistance to Fas-mediated apoptosis.
Conclusions:
- Apoptotic execution is significantly dependent on the cell cycle phase.
- Fas-mediated apoptosis preferentially targets cells in the G1 phase.
- Distinct apoptotic stimuli exhibit differential cell cycle phase preferences for induction.
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