Fatty Acid Oxidation and Signaling in Apoptosis
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D.G. Tang
Abstract
It is well established that fatty acid metabolites of cyclooxygenase, lipoxygenase (LOX), and cytochrome P450 are implicated in essential aspects of cellular signaling including the induction of programmed cell death. Here we review the roles of enzymatic and nonenzymatic products of polyunsaturated fatty acids in controlling cell growth and apoptosis. Also, the spontaneous oxidation of polyunsaturated fatty acids yields reactive aldehydes and other products of lipid peroxidation that are potentially toxic to cells and may also signal apoptosis. Significant conflicting data in terms of the role of LOX enzymes are highlighted, prompting a reevaluation of the relationship between LOX and prostate cancer cell survival. We include new data showing that LNCaP, PC3, and Du145 cells express much lower levels of 5-LOX mRNA and protein compared with normal prostate epithelial cells (NHP2) and primary prostate carcinoma cells (TP1). Although the 5-LOX activating protein inhibitor MK886 killed these cells, another 5-LOX inhibitor AA861 hardly showed any effect. These observations suggest that 5-LOX is unlikely to be a prostate cancer cell survival factor, implying that the mechanisms by which LOX inhibitors induce apoptosis are more complex than expected. This review also suggests several mechanisms involving peroxisome proliferator activated receptor activation, BCL proteins, thiol regulation, and mitochondrial and kinase signaling by which cell death may be produced in response to changes in nonesterified and nonprotein bound fatty acid levels. Overall, this review provides a context within which the effects of fatty acids and fatty acid oxidation products on signal transduction pathways, particularly those involved in apoptosis, can be considered in terms of their overall importance relative to the much better studied protein or peptide signaling factors.
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
