Related Experiment Videos
Molecular failure of apoptosis: inappropriate cell survival and mutagenesis?
G T Williams1, M R Critchlow, V L Hedge
1Biological Sciences, Keele University, Staffordshire, UK. g.t.williams@keele.ac.uk
Abstract:
Since cell death by apoptosis is achieved through complex interactions between numerous molecular components, cells may fail to die when stimulated because of molecular abnormalities in the apoptosis pathway or in its control mechanisms. Such inappropriate cell survival is well established when apoptosis is suppressed by elevated expression of bcl-2, at least for some cell types. Many cells undergo apoptosis at moderate levels of DNA damage and suppression of such apoptosis might be expected to increase the rate of mutation because of the persistence of cells with damaged DNA. We and others have now confirmed this prediction in bcl-2 transfected cells. Suppression of the apoptosis pathway can only lead to inappropriate cell survival if it relates to events before the cell becomes committed to die. We have analyzed this question for agents that inhibit the caspases, the site-specific proteases which form the biochemical core of the process of apoptosis. We have shown that inhibition of certain caspases does lead to the survival of Jurkat human T-cells induced to undergo Fas-mediated apoptosis.
Insights
Cells may survive inappropriately due to apoptosis pathway defects. Inhibiting caspases, key apoptosis enzymes, can cause Jurkat T-cells to survive Fas-mediated apoptosis, confirming predictions.
Area of Science:
- Cell biology
- Molecular biology
- Immunology
Background:
- Apoptosis, or programmed cell death, is crucial for development and tissue homeostasis.
- Dysregulation of apoptosis can lead to diseases like cancer and autoimmune disorders.
- The bcl-2 family proteins are key regulators of apoptosis, and their overexpression can inhibit cell death.
Purpose of the Study:
- To investigate the role of caspases in regulating apoptosis.
- To determine if inhibiting caspases leads to inappropriate cell survival.
- To analyze whether caspase inhibition affects cells before they are committed to die.
Main Methods:
- Utilized Jurkat human T-cells for experiments.
- Induced apoptosis using Fas-mediated stimulation.
- Administered agents to inhibit specific caspases.
- Assessed cell survival and apoptosis markers.
Main Results:
- Inhibition of certain caspases resulted in the survival of Jurkat T-cells.
- This survival occurred in cells stimulated to undergo Fas-mediated apoptosis.
- Findings support the hypothesis that caspase inhibition can lead to inappropriate cell survival.
Conclusions:
- Caspase inhibition can prevent programmed cell death.
- This prevention of apoptosis by caspases can lead to inappropriate cell survival.
- Targeting caspases may have implications for diseases involving aberrant cell death.