Molecular Basis of Oxidative Stress: Chemistry, Mechanisms, and Disease Pathogenesis

Sets the stage for the development of better diagnostic techniques and therapeutics Featuring contributions from an international team of leading clinicians and biomedical researchers, Molecular Basis of Oxidative Stress reviews the molecular and chemical bases of oxidative stress, describing how oxidative stress can lead to the development of cancer and cardiovascular and neurodegenerative diseases. Moreover, it explains the potential role of free radicals in both the diagnosis and the development of therapeutics to treat disease. Molecular Basis of Oxidative Stress is logically organized, beginning with a comprehensive discussion of the fundamental chemistry of reactive species. Next, the book: Presents new mechanistic insights into how oxidative damage of biomolecules occurs Examines how these oxidative events effect cellular metabolism Investigates the role of oxidative stress in the pathogenesis of cancer, neurodegenerative disease, cardiovascular disease, and cystic fibrosis Explores opportunities to improve the diagnosis of disease and the design of new therapeutic agents Readers will find much novel information, including new radical chemistries and the latest discoveries of how free radicals react with biomolecules. The contributors also present recent findings that help us better understand the initiation of oxidative stress and the mechanisms leading to the pathogenesis of various diseases. Throughout the book, the use of molecular structures helps readers better understand redox chemistry. In addition, plenty of detailed figures illustrate the mechanisms of oxidative stress and disease pathogenesis. Examining everything from the basic chemistry of oxidative stress to the pathogenesis of disease, Molecular Basis of Oxidative Stress will help readers continue to explore the nature of oxidative stress and then use that knowledge to develop new approaches to prevent, detect, and treat a broad range of disease conditions.

Preface xvii About the Contributors xix Contributors xxv 1 Chemistry of Reactive Species 1 Frederick A. Villamena 2 Lipid Peroxidation and Nitration 49 Sean S. Davies and Lilu Guo 3 Protein Posttranslational Modifi cation 71 James L. Hougland, Joseph Darling, and Susan Flynn 4 DNA Oxidation 93 Dessalegn B. Nemera, Amy R. Jones, and Edward J. Merino 5 Downregulation of Antioxidants and Phase 2 Proteins 113 Hong Zhu, Jianmin Wang, Arben Santo, and Yunbo Li 6 Mitochondrial Dysfunction 123 Yeong–Renn Chen 7 NADPH Oxidases: Structure and Function 137 Mark T. Quinn 8 Cell Signaling and Transcription 179 Imran Rehmani, Fange Liu, and Aimin Liu 9 Oxidative Stress and Redox Signaling in Carcinogenesis 203 Rodrigo Franco, Aracely Garcia–Garcia, Thomas B. Kryston, Alexandros G. Georgakilas, Mihalis I. Panayiotidis, and Aglaia Pappa 10 Neurodegeneration from Drugs and Aging–Derived Free Radicals 237 Annmarie Ramkissoon, Aaron M. Shapiro, Margaret M. Loniewska, and Peter G. Wells 11 Cardiac Ischemia and Reperfusion 311 Murugesan Velayutham and Jay L. Zweier 12 Atherosclerosis: Oxidation Hypothesis 329 Chandrakala Aluganti Narasimhulu, Dmitry Litvinov, Xueting Jiang, Zhaohui Yang, and Sampath Parthasarathy 13 Cystic Fibrosis 345 Neal S. Gould and Brian J. Day 14 Biomarkers of Oxidative Stress in Neurodegenerative Diseases 359 Rukhsana Sultana, Giovanna Cenini, and D. Allan Butterfield 15 Synthetic Antioxidants 377 Grégory Durand References, 398 Index 407

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.