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Mechanisms of nitric oxide-dependent apoptosis: involvement of mitochondrial mediators
1Instituto de Bioquímica, Facultad de Farmacia, Madrid, Spain. boscal@eucmax.sim.ucm.es
Abstract:
Programmed cell death occurs in several physiopathological situations in multicellular organisms and constitutes a common mechanism of cell replacement, tissue remodelling and removal of altered cells. The effectors that induce apoptosis as well as the signalling pathways involved in the process are the subjects of current work. In addition to receptor-mediated apoptosis, highly reactive molecules, such as NO, influence cell viability either by acting as a protection against apoptogenic stimuli, or by inducing apoptosis when produced at elevated concentrations. The contribution to apoptosis of mediators released by the mitochondria and involved in the activation of caspases focused attention on the functional changes caused by NO in this organelle. NO induces mitochondrial permeability transition and promotes apoptosis in cell-free systems containing mitochondria and nuclei. Moreover, NO-dependent apoptosis can be blocked in most cases through the use of permeability transition or caspase inhibitors. The intracellular pathways activated in response to NO challenge and involved in the regulation of apoptosis are analysed.
Insights
Nitric oxide (NO) influences programmed cell death (apoptosis) by affecting mitochondria. Elevated NO levels promote apoptosis, a process that can be inhibited by targeting mitochondrial permeability or caspases.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Programmed cell death (apoptosis) is crucial for multicellular organism development and health.
- Apoptosis involves specific signaling pathways and effector molecules.
- Nitric oxide (NO) can modulate apoptosis, acting as either a protective or an inducer agent.
Purpose of the Study:
- To investigate the role of nitric oxide (NO) in apoptosis.
- To elucidate the mechanisms by which NO influences cell viability, particularly through mitochondrial pathways.
- To analyze intracellular signaling pathways activated by NO that regulate apoptosis.
Main Methods:
- Studied the effects of NO on cell viability and apoptosis.
- Utilized cell-free systems containing mitochondria and nuclei to examine NO's direct impact.
- Employed permeability transition and caspase inhibitors to block NO-induced apoptosis.
Main Results:
- Nitric oxide (NO) induces mitochondrial permeability transition.
- NO promotes apoptosis in cell-free systems.
- NO-dependent apoptosis can be effectively inhibited by targeting mitochondrial permeability or caspase activation.
Conclusions:
- Mitochondria play a significant role in NO-mediated apoptosis.
- NO's impact on mitochondrial function is a key mechanism driving apoptosis.
- Targeting mitochondrial pathways offers a potential strategy to control NO-induced cell death.