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The role of intracellular oxidants in apoptosis
A F Slater1, C S Nobel, S Orrenius
1Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Abstract:
Apoptotic cell death is a complex process whose biochemistry is poorly understood. Direct exposure of various cell types of oxidants such as hydrogen peroxide or lipid hydroperoxides can directly induce apoptosis, while in many experimental models pretreatment of cells with antioxidants has been shown to protect against this form of cell death. Recent experimental evidence suggests that multiple forms of thymocyte apoptosis can be inhibited by free radical spin traps, spin probes and thiol reductants, and that this inhibition correlates with a lower oxidative burden within the treated cells. Possible sites of production of these oxidants include mitochondrial electron transport and phospholipase A2-activated arachidonic acid metabolism, while intracellular targets may include redox sensitive transcription factors and inhibitory proteins that must be tagged for proteolysis before apoptosis can commence.
Insights
Oxidative stress contributes to programmed cell death (apoptosis). Antioxidants and free radical scavengers can inhibit apoptosis by reducing cellular oxidative burden, revealing key biochemical pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Apoptotic cell death is a complex biological process with incompletely understood biochemistry.
- Oxidants like hydrogen peroxide can directly induce apoptosis, while antioxidants often provide protection.
- Evidence suggests a role for oxidative stress in various forms of programmed cell death.
Purpose of the Study:
- To investigate the role of oxidative stress in apoptosis.
- To explore the mechanisms by which antioxidants inhibit apoptosis.
- To identify potential sources and targets of oxidants involved in cell death.
Main Methods:
- Exposure of various cell types to oxidants (e.g., hydrogen peroxide, lipid hydroperoxides).
- Treatment of cells with antioxidants, free radical spin traps, spin probes, and thiol reductants.
- Assessment of the correlation between inhibition of apoptosis and reduced cellular oxidative burden.
Main Results:
- Direct oxidant exposure induces apoptosis in multiple cell types.
- Antioxidant pretreatment protects cells against oxidant-induced apoptosis.
- Inhibition of thymocyte apoptosis by spin traps and thiol reductants correlates with decreased oxidative burden.
Conclusions:
- Oxidative stress is a significant factor in initiating and regulating apoptotic cell death.
- Interventions targeting oxidative stress, such as antioxidants and radical scavengers, can effectively inhibit apoptosis.
- Mitochondrial electron transport and arachidonic acid metabolism are potential sources of pro-apoptotic oxidants.