Related Experiment Videos
Reactive oxygen species are downstream mediators of p53-dependent apoptosis
T M Johnson1, Z X Yu, V J Ferrans
1Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
Reactive oxygen species (ROS) have been implicated as potential modulators of apoptosis. Conversely, experiments under hypoxic conditions have suggested that apoptosis could occur in the absence of ROS. We sought to determine whether a central modulator of apoptosis, p53, regulates the levels of intracellular ROS and whether a rise in ROS levels is required for the induction of p53-dependent apoptosis. We transiently overexpressed wild-type p53, using adenoviral gene transfer, and identified cell types that were sensitive or resistant to p53-mediated apoptosis. Cells sensitive to p53-mediated apoptosis produced ROS concomitantly with p53 overexpression, whereas cells resistant to p53 failed to produce ROS. In sensitive cells, both ROS production and apoptosis were inhibited by antioxidant treatment. These results suggest that p53 acts to regulate the intracellular redox state and induces apoptosis by a pathway that is dependent on ROS production.
Insights
The tumor suppressor p53 regulates reactive oxygen species (ROS) production, a key factor in initiating programmed cell death (apoptosis). This study shows ROS generation is essential for p53-induced apoptosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Reactive oxygen species (ROS) are implicated in apoptosis, but their necessity under hypoxia is debated.
- The role of p53, a central apoptosis regulator, in controlling intracellular ROS levels remains unclear.
Purpose of the Study:
- To investigate if p53 regulates intracellular ROS levels.
- To determine if increased ROS is required for p53-dependent apoptosis.
Main Methods:
- Transient overexpression of wild-type p53 using adenoviral gene transfer.
- Identification of apoptosis-sensitive and resistant cell types.
- Assessment of ROS production and apoptosis induction.
- Inhibition studies using antioxidant treatments.
Main Results:
- Apoptosis-sensitive cells showed ROS production concurrent with p53 overexpression.
- Apoptosis-resistant cells failed to produce ROS upon p53 overexpression.
- Antioxidants inhibited both ROS production and apoptosis in sensitive cells.
Conclusions:
- p53 regulates the intracellular redox state.
- p53 induces apoptosis through a ROS-dependent pathway.