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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
Clustering of apoptotic cells via bystander killing by peroxides
K Reznikov1, L Kolesnikova, A Pramanik
1Experimental Alcohol and Drug Addiction Research Section, Department of Clinical Neuroscience and. Department of Medical Biochemistry and Biophysics, Karolinska Institute S-171 76, Stockholm, Sweden.
Abstract:
Clustering of apoptotic cells is a characteristic of many developing or renewing systems, suggesting that apoptotic cells kill bystanders. Bystander killing can be triggered experimentally by inducing apoptosis in single cells and may be based on the exchange of as yet unidentified chemical cell death signals between nearby cells without the need for cell-to-cell communication via gap junctions. Here we demonstrate that apoptotic cell clusters occurred spontaneously, after serum deprivation or p53 transfection in cell monolayers in vitro. Clustering was apparently induced through bystander killing by primary apoptotic cells. Catalase, a peroxide scavenger, suppressed bystander killing, suggesting that hydrogen peroxide generated by apoptotic cells is the death signal. Although p53 expression increased the number of apoptoses, clustering was found to be similar around apoptotic cells whether or not p53 was expressed, indicating that there is no specific p53 contribution to bystander killing. Bystander killing through peroxides emitted by apoptotic cells may propagate tissue injury in different pathological situations and be relevant in chemo-, gamma-ray, and gene therapy of cancer.
Insights
Apoptotic cells can kill nearby healthy cells, a process called bystander killing, which may involve hydrogen peroxide signals. This cell death mechanism is not dependent on p53 and has implications for cancer therapies.
Area of Science:
- Cell Biology
- Biochemistry
- Pathology
Background:
- Clustering of apoptotic cells suggests bystander killing, where dying cells harm neighbors.
- This process may involve unidentified chemical signals, independent of gap junction communication.
Purpose of the Study:
- To investigate the mechanism of apoptotic cell clustering and bystander killing.
- To determine the role of hydrogen peroxide and p53 in this phenomenon.
Main Methods:
- Induction of apoptosis in cell monolayers via serum deprivation or p53 transfection.
- Observation of apoptotic cell clustering in vitro.
- Assessment of the effect of catalase (peroxide scavenger) on bystander killing.
Main Results:
- Apoptotic cell clusters formed spontaneously and were induced by primary apoptotic cells.
- Catalase significantly suppressed bystander killing, identifying hydrogen peroxide as a key death signal.
- Clustering occurred similarly regardless of p53 expression, indicating no specific p53 role in bystander killing.
Conclusions:
- Hydrogen peroxide emitted by apoptotic cells mediates bystander killing and cell clustering.
- This peroxide-mediated bystander killing may contribute to tissue injury in various pathologies.
- Understanding this mechanism is relevant for cancer therapies like chemotherapy, gamma-ray, and gene therapy.
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