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FREDERICK A. VILLAMENA, PhD, is Associate Professor in the Pharmacology Department of The Ohio State University. Dr. Villamena performs extensive research to develop radical probes and synthetic antioxidants for the treatment of radical-mediated injury such as myocardial infarction. His research draws from many fields, including computational chemistry, organic synthesis, spectroscopy, and molecular biology.
Preface
About the Contributors
1 Chemistry of Reactive Species
Frederick Villamena
1.1 Redox Chemistry
1.2 Classification of Reactive Species
1.3 Reactivity
1.4 Origins of Reactive Species
1.5 Methods of Detection
2 Lipid Nitration and Peroxidation
Sean S Davies and Lilu Guo
Overview
2.1 Peroxidation of Polyunsaturated Fatty Acids
2.2 Cyclic Endoperoxides and their Products
2.3 Fragmented Products of Lipid Peroxidation
2.4 Epoxy Fatty Acids
2.5 Lipid Nitrosylation
Summary
3 Post-Translational Protein Modification
James L Hougland, Joseph Darling, and Susan Flynn
Overview
3.1 Oxidative Stress-Related PTMs: Oxidation Reactions
3.2 Amino Acid Modification by Oxidation-Produced Electrophiles
3.3 Detection of Oxidative Stress-Related PTMs
3.4 Role of PTM in Cellular Redox Signaling
Summary
4 Nucleotide Oxidation
Dessalegn B Nemera, Amy R Jones and Edward J Merino
Overview
4.1 The Context of Cellular DNA Oxidation
4.2 Oxidation of Oligonucleotides
4.3 Examination of Specific Oxidative Lesions
Future Outlook of DNA Oxidative Lesions
5 Down Regulation of Phase 2 Enzymes
Hong Zhu, Jianmin Wang, Arben Santo, and Yunbo Li
Overview
5.1 Definitions of Antioxidants and Phase 2 Proteins
5.2 Roles in Oxidative Stress
5.3 Molecular Regulation
5.4 Induction in Chemoprevention
5.5 Downregulation
Conclusions and Perspectives
6 Mitochondrial Dysfunction
Yeong-Renn Chen
Overview
6.1 Mitochondria and Submitochondrial Particles
6.2 Energy Transduction
6.3 Mitochondrial Stress
6.4 Superoxide Radical Anion Generation as Mediated by Electron Transport Chain and Disease Pathogenesis
Summary
7 NADPH Oxidases: Structure and Function
Mark T Quinn
Overview
7.1 Introduction
7.2 Phagocyte NADPH Oxidase Structure
7.3 Phagocyte ROS Production
7.4 Phagocyte NADPH Oxidase Function
7.5 Non-phagocyte NADPH Oxidase Structure
7.6 Non-Phagocyte ROS Production
7.7 Functions of Non-Phagocyte NADPH Oxidases
Summary
8 Cell Signaling and Transcription
Imran Rehmani, Fange Liu and Aimin Liu
Overview
8.1 Common Mechanisms of Redox Signaling
8.2 Redox and Oxygen-Sensitive Transcription Factors in Prokaryotes
8.3 Redox Signaling in Metazoans
8.4 Oxygen Sensing in Metazoans
8.5 Medical Significance of Redox and Oxygen-sensing Pathways
Conclusions
9 Cancer
Aracely Garcia-Garcia, Rodrigo Franco, Thomas B Kryston, Alexandros G Georgakilas, Aglaia Pappa and Mihalis I Panayiotidis
Overview
9.1 Redox Environment and Cancer
9.2 Oxidative Modifications to Biomolecules and Carcinogenesis
9.3 Measurement of Oxidative DNA Damage in Human Cancer
9.4 Epigenetic Involvement in Oxidative Stress-Induced Carcinogenesis
9.5 Deregulation of Cell Death Pathways by Oxidative Stress and Cancer
Conclusions and Perspective
10 Neurodegeneration from Drugs and Aging-Derived Free Radicals
Annmarie Ramkissoon, Aaron M Shapiro, Margaret M Loniewska and Peter G Wells
Overview
10.1 ROS Formation
10.2 Protection Against ROS
10.3 Nrf2 Regulation of Protective Responses
Summary and Conclusions
11 Cardiac Ischemia and Reperfusion
Murugesan Velayutham and Jay L Zweier
Overview
11.1 Oxygen in the Heart
11.2 Sources of ROS During Ischemia and Reperfusion
11.3 Modulation of Substrates, Metabolites, and Cofactors during I-R
11.4 ROS-Mediated Cellular Communication During I-R
11.5 ROS and Cell Death During Ischemia and Reperfusion
11.6 Potential Therapeutic Strategies
Summary and Conclusion
12 Atherosclerosis and Lipid Oxidation
Aluganti N Chandrakala, Dmitry Litvinov, Xueting Jiang, Yang Zhaohui, and Sampath Parthasarathy
Overview
12.1 Lipid Peroxidation
12.2 Oxidation Hypothesis of Atherosclerosis
12.3 Animal Models of Atherosclerosis
12.4 Aldehyde Generation from Peroxidized Lipids
Summary
13 Cystic Fibrosis
Neal S Gould and Brian J Day
Overview
13.1 Lung Disease Characteristics in CF
13.2 Role of CFTR in the Lung
13.3 Oxidative Stress in the CFTR Deficient Lung
13.4 Antioxidant Therapies for CF
Summary
14 Biomarkers of Oxidative Stress in Neurodegenerative Diseases
Rukhsana Sultana, Giovanna Cenini and D Allan Butterfield
Overview
14.1 Introduction
14.2 Biomarkers of Protein Oxidation/ Nitration
14.3 Biomarkers of Lipid Peroxidation
14.4 Biomarkers of Carbohydrates Oxidation
14.5 Biomarkers of Nucleic Acid Oxidation
15 Synthetic Antioxidants
Grégory Durand
Overview
15.1 Endogenous Enzymatic System of Defense
15.2 Metal-Based Synthetic Antioxidants
15.3 Non-Metal Based Antioxidants
15.4 Nitrone-Based Spin Traps as Antioxidants
Index
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