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Activation of c-Jun N-Terminal Kinase and Apoptosis in Endothelial Cells Mediated by Endogenous Generation of Hydrogen Peroxide
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A. Ramachandran
Published/Copyright:
June 1, 2005
Abstract
Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy 1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steadystate concentrations (0.1 0.5 nmolmin 1106 cells) of H2O2 generated intracellularly activate cJun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both cJun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.
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Published Online: 2005-06-01
Published in Print: 2002-04-12
Copyright © 2002 by Walter de Gruyter GmbH & Co. KG
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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
