Nitric Oxide and Cell Signaling Pathways in Mitochondrial-Dependent Apoptosis
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C.S. Boyd
Abstract
Nitric oxide, generated by endogenous nitric oxide synthases or nitric oxide donors, can promote or prevent apoptosis induced by diverse proapoptotic stimuli in cell culture models. Both mitochondrialdependent and independent apoptotic signaling pathways mediate this dichotomous cellular response to nitric oxide. The molecular mechanisms behind these effects are complex and involve a number of nitrogen oxiderelated species that are more reactive than nitric oxide itself. The local cellular environment plays a dynamic role in determining the nature and concentration of these species. Important components of the microenvironment include: the cellular redox state, glutathione, transition metals and the presence of other oxygen and nitrogencentered radicals. In particular, redoxsensitive nitrosating species are favorably generated under physiological conditions and capable of modifying multiple cell signaling pathways through reversible Snitrosation reactions. Cytochrome c release from mitochondria is an important mechanism for the activation of caspase-3 and the initiation of cell death in response to intrinsic proapoptotic stimuli, including oxidative and nitrosative stress. In turn, caspases and mitogen associated protein kinases may modulate cytochrome c release through their effects on the Bcl-2 family of proteins. This review will focus on (i) the importance of the cellular environment in determining the fate of nitric oxide and (ii) the ability of Snitrosation to regulate mitochondrialdependent apoptosis at the level of mitochondrial bioenergetics, cytochrome c release, caspases, mitogen associated protein kinases, and the Bcl-2 family of proteins.
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
Articles in the same Issue
- Highlight: Oxidative Stress
- Highlight: Oxidative Stress
- Peroxiredoxins
- 15-Lipoxygenase-1: A Prooxidant Enzyme
- Reactive Sulfur Species: An Emerging Concept in Oxidative Stress
- The Pathobiochemistry of Nitrogen Dioxide
- Nitric Oxide and Peroxynitrite Interactions with Mitochondria
- Nitric Oxide and Cell Signaling Pathways in Mitochondrial-Dependent Apoptosis
- Fatty Acid Oxidation and Signaling in Apoptosis
- Oxidant-Induced Signaling: Effects of Peroxynitrite and Singlet Oxygen
- The 80th Anniversary of Vitamin E: Beyond Its Antioxidant Properties
- Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?
- Mammalian Cell Injury Induced by Hypothermia the Emerging Role for Reactive Oxygen Species
- The Chelatable Iron Pool in Living Cells: A Methodically Defined Quantity
- Dietary Flavonoids as Potential Neuroprotectants
- Oxidative Nerve Cell Death in Alzheimers Disease and Stroke: Antioxidants as Neuroprotective Compounds
- A2E and Blue Light in the Retina: The Paradigm of Age-Related Macular Degeneration
- Interactions of Nitric Oxide and Peroxynitrite with Low-Density Lipoprotein
- Non-Antioxidant Properties of Carotenoids
- Proteolytic Response to Oxidative Stress in Mammalian Cells
- Neurospora crassa Catalases, Singlet Oxygen and Cell Differentiation
- The Cellular Hydration State: A Critical Determinant for Cell Death and Survival
- Redox Regulation of Stress Signals: Possible Roles of Dendritic Stellate TRX Producer Cells (DST Cell Types)
- Oxidative Stress, Spermatogenesis and Fertility
- Postprandial Oxidative Stress
- [18O]-Labeled Singlet Oxygen as a Tool for Mechanistic Studies of 8-Oxo-7,8-Dihydroguanine Oxidative Damage: Detection of Spiroiminodihydantoin, Imidazolone and Oxazolone Derivatives
- The Specificity of Lipoxygenase-Catalyzed Lipid Peroxidation and the Effects of Radical- Scavenging Antioxidants
- Human Neutrophils Oxidize Low-Density Lipoprotein by a Hypochlorous Acid- Dependent Mechanism: The Role of Vitamin C
- Perturbation of Lipid Metabolism by Linoleic Acid Hydroperoxide in CaCo-2 Cells
- Irreversible Thiol Oxidation in Carbonic Anhydrase III: Protection by S-Glutathiolation and Detection in Aging Rats
- Green Tea Extract Protects against Early Alcohol-Induced Liver Injury in Rats
- Comparing β-Carotene, Vitamin E and Nitric Oxide as Membrane Antioxidants
- Induction of Thioredoxin Reductase Gene Expression by Peroxynitrite in Human Umbilical Vein Endothelial Cells
- Activation of c-Jun N-Terminal Kinase and Apoptosis in Endothelial Cells Mediated by Endogenous Generation of Hydrogen Peroxide
- Detection of Poly(ADP-Ribose) by Immunocytochemistry: A Sensitive New Method for the Early Identification of UVB- and H2O2-Induced Apoptosis in Keratinocytes
- Efficacy of HOCl Scavenging by Sulfur- Containing Compounds: Antioxidant Activity of Glutathione Disulfide?
- Cysteine Supplementation Prevents Unweighting-Induced Ubiquitination in Association with Redox Regulation in Rat Skeletal Muscle
Articles in the same Issue
- Highlight: Oxidative Stress
- Highlight: Oxidative Stress
- Peroxiredoxins
- 15-Lipoxygenase-1: A Prooxidant Enzyme
- Reactive Sulfur Species: An Emerging Concept in Oxidative Stress
- The Pathobiochemistry of Nitrogen Dioxide
- Nitric Oxide and Peroxynitrite Interactions with Mitochondria
- Nitric Oxide and Cell Signaling Pathways in Mitochondrial-Dependent Apoptosis
- Fatty Acid Oxidation and Signaling in Apoptosis
- Oxidant-Induced Signaling: Effects of Peroxynitrite and Singlet Oxygen
- The 80th Anniversary of Vitamin E: Beyond Its Antioxidant Properties
- Role of Endogenous Oxidative DNA Damage in Carcinogenesis: What Can We Learn from Repair-Deficient Mice?
- Mammalian Cell Injury Induced by Hypothermia the Emerging Role for Reactive Oxygen Species
- The Chelatable Iron Pool in Living Cells: A Methodically Defined Quantity
- Dietary Flavonoids as Potential Neuroprotectants
- Oxidative Nerve Cell Death in Alzheimers Disease and Stroke: Antioxidants as Neuroprotective Compounds
- A2E and Blue Light in the Retina: The Paradigm of Age-Related Macular Degeneration
- Interactions of Nitric Oxide and Peroxynitrite with Low-Density Lipoprotein
- Non-Antioxidant Properties of Carotenoids
- Proteolytic Response to Oxidative Stress in Mammalian Cells
- Neurospora crassa Catalases, Singlet Oxygen and Cell Differentiation
- The Cellular Hydration State: A Critical Determinant for Cell Death and Survival
- Redox Regulation of Stress Signals: Possible Roles of Dendritic Stellate TRX Producer Cells (DST Cell Types)
- Oxidative Stress, Spermatogenesis and Fertility
- Postprandial Oxidative Stress
- [18O]-Labeled Singlet Oxygen as a Tool for Mechanistic Studies of 8-Oxo-7,8-Dihydroguanine Oxidative Damage: Detection of Spiroiminodihydantoin, Imidazolone and Oxazolone Derivatives
- The Specificity of Lipoxygenase-Catalyzed Lipid Peroxidation and the Effects of Radical- Scavenging Antioxidants
- Human Neutrophils Oxidize Low-Density Lipoprotein by a Hypochlorous Acid- Dependent Mechanism: The Role of Vitamin C
- Perturbation of Lipid Metabolism by Linoleic Acid Hydroperoxide in CaCo-2 Cells
- Irreversible Thiol Oxidation in Carbonic Anhydrase III: Protection by S-Glutathiolation and Detection in Aging Rats
- Green Tea Extract Protects against Early Alcohol-Induced Liver Injury in Rats
- Comparing β-Carotene, Vitamin E and Nitric Oxide as Membrane Antioxidants
- Induction of Thioredoxin Reductase Gene Expression by Peroxynitrite in Human Umbilical Vein Endothelial Cells
- Activation of c-Jun N-Terminal Kinase and Apoptosis in Endothelial Cells Mediated by Endogenous Generation of Hydrogen Peroxide
- Detection of Poly(ADP-Ribose) by Immunocytochemistry: A Sensitive New Method for the Early Identification of UVB- and H2O2-Induced Apoptosis in Keratinocytes
- Efficacy of HOCl Scavenging by Sulfur- Containing Compounds: Antioxidant Activity of Glutathione Disulfide?
- Cysteine Supplementation Prevents Unweighting-Induced Ubiquitination in Association with Redox Regulation in Rat Skeletal Muscle
