Cellular Implications of Redox Signaling

Contents......Page 12
Preface......Page 6
1. Summary......Page 14
2. Introduction and Historical Perspective......Page 16
3. The Thioredoxin System......Page 20
3.1 Thioredoxin Reductase and Selenium......Page 21
3.2 Structure of Mammalian Thioredoxin Reductase......Page 22
4. The Glutaredoxin System......Page 28
6. Future Perspectives......Page 31
References......Page 32
1. Summary......Page 40
2. The Mammalian Thioredoxin System......Page 41
3.1 Co-Translational Insertion of Selenocysteine......Page 42
3.2 Selenocysteine in TrxR as a Drug Target......Page 45
4. Regulation of Cytosolic Thioredoxin Reductase in Relation to Cellular Redox Signaling......Page 47
5. Effects of Dinitrohalobenzenes by Interactions with Thioredoxin Reductase......Page 49
References......Page 52
2. Historical Comments......Page 60
3.1 Structure......Page 61
3.2 Electronic Structure......Page 63
3.5 Cluster Ligands......Page 66
3.6 Heterometal Clusters......Page 68
3.7 Self-activation of 3Fe-enzymes......Page 71
3.8 Degradation and Biosynthesis of Fe-S Clusters......Page 72
4.1 Electron Transfer......Page 73
4.2 Oxidation-Reduction Potentials......Page 74
4.3 Non-Redox Functions of Fe-S Proteins......Page 77
5. Conclusion and Outlook......Page 79
References......Page 80
1. Summary......Page 86
2.1 Ferredoxin......Page 87
2.2 Ferredoxin:Thioredoxin Reductase......Page 88
2.3 Thioredoxins......Page 90
3. The Redox Signal Transfer through the Ferredoxin/Thioredoxin System......Page 96
4. Target Enzymes......Page 99
4.1 Fructose 1,6-bisphosphatase......Page 101
4.2 NADP-Dependent Malate Dehydrogenase......Page 102
5. Concluding Remarks......Page 103
References......Page 104
1. Summary......Page 112
2. Ferredoxin-Thioredoxin System......Page 113
2.1 NADP/Thioredoxin System......Page 115
3.1 Alleviation of Allergies......Page 118
4.1 Cereal Transformations......Page 119
4.2 Properties of Transgenic Cereals......Page 120
5. A New Development......Page 121
References......Page 123
1. Summary......Page 128
2. Cytoprotective Effects of Thioredoxin......Page 130
3. Thioredoxin and its Related Molecules......Page 131
4. Thioredoxin Knock Out and Transgenic Mice......Page 134
5.2 Resistance Against Excitotoxic Hippocampal Injury......Page 136
5.3 Resistance Against Oxidative Stress and Elongated Survival......Page 137
5.4 Pancreatic Beta Cell Specific Overexpression of Thioredoxin......Page 138
6. Extracellular Function of Thioredoxin......Page 139
7. A Truncated Form of Thioredoxin......Page 140
8. Chemokine-Like Activity of Thioredoxin......Page 141
10. Thioredoxin Binding Proteins......Page 142
11. Redox Regulation of Transcription Factors by Thioredoxin......Page 143
12. Redox Regulation of Apoptosis by Thioredoxin......Page 144
14. Acknowledgements......Page 145
References......Page 146
1. Summary......Page 154
1.1 Roles of protein cysteines in cells......Page 155
1.2 Molecular Mechanisms of S-thiolation and S-nitrosylation......Page 157
1.3 Molecular Mechanism of Dethiolation and Denitrosylation......Page 163
1.4 Effects of Oxidative Modification on Protein Function......Page 166
2.1 Protein Separation by Charge......Page 167
3. Oxidative Modification of Reactive Cysteines in Selected Proteins......Page 172
3.1 Abundant Proteins......Page 173
3.2 Less Abundant Proteins......Page 176
4. Perspective — Questions in Need of Answers......Page 181
References......Page 183
1. Summary......Page 188
2. Radical Scavenging by GSH......Page 190
4. Relative Scavenging Roles of GSH and Ascorbate......Page 193
5. Radical Scavenging by Vicinal Thiols......Page 194
References......Page 197
1. Summary......Page 204
2. Introduction......Page 205
3.1 Peroxisomal Hydrogen Peroxide Production Associated with Photorespiration......Page 207
3.2 Chloroplastic Hydrogen Peroxide Production Associated with the Mehler Reaction......Page 209
4. Ascorbic Acid......Page 210
5. Glutathione......Page 212
5.1 Regulation of Glutathione Biosynthesis......Page 215
6. Coupling Between Ascorbate and Glutathione Pools......Page 216
7. Ascorbate and Glutathione in Signal Transduction......Page 218
References......Page 221
1. Summary......Page 226
2. Disulfide Bond Formation in Extracytoplasmic Proteins......Page 228
3. Protein Disulfide Bond Isomerization......Page 232
4. Disulfide Bond Formation in the Cytoplasm......Page 235
5. An Alternative Disulfide Reducing Pathway as an Environmental Switch......Page 238
6. Conclusion......Page 240
References......Page 241
1. Summary......Page 246
2. Disulfides and Protein Structure and Stability......Page 247
3.2 Formation of Disulfides in the Endoplasmic Reticulum......Page 248
4. Oxidative Protein Folding......Page 251
5.1 Structural Organization — The Thioreoxin Family......Page 252
5.2 Active Site Properties......Page 253
5.3 Catalytic Properties of PDI and its Mutants......Page 255
6.2 Redox Potential of Substrates......Page 256
7.1 Scanning and Escape......Page 258
8.1 Substrate Inhibition......Page 260
9. Secretion in Yeast......Page 262
9.1 Redox and Structural Requirements for Yeast Growth......Page 264
References......Page 266
1. Summary......Page 270
2.1 Selective Radioactive Protein Thiol Labeling Reagent N-iodoacetyl-[125I]-3-iodotyrosine (IAIT)......Page 271
2.3 Thiol/Disulfide Exchange to Purify Monothiol Proteins......Page 272
3.1 The Majority of Cell Proteins are Present in the Reduced State......Page 273
3.2 The Majority of the Cell Thiol Proteins Contain Surface-Localized Vicinal Thiols......Page 275
3.3 Properties of Thiol Proteins Oxidized by Reaction with Active Disulfides......Page 276
3.4 NADPH-Dependent Protein Disulfide Reductase Activity Depends on the Mixed Disulfide Formed by Thioredoxin......Page 278
3.5 Implications of the Studies in vitro with Oxidized Cell Extracts......Page 286
4. Redox Regulation during Growth Initiation......Page 287
4.1 Growth Factors Induce a Calcium-Dependent Transient Oxidation of TXN and Other Cell Proteins......Page 289
4.2 Calcium Inhibits the in vitro Activity of Thioredoxin Reductase......Page 292
4.3 Implications of the Transient Oxidation of Thioredoxin and Other Cell Dithiol Proteins......Page 293
5. Concluding Remarks......Page 296
References......Page 297
1. Summary......Page 300
2.1 Identification of OxyR and Its Target Genes......Page 301
2.2 OxyR Activation by Disulfide Bond Formation Between C199 and C208......Page 302
2.3 OxyR Reduction by Glutaredoxin......Page 304
2.4 Structure of the OxyR Regulatory Domain......Page 306
3.1 Identification of σR and RsrA and Their Target Genes......Page 307
3.2 Release of σR Upon Disulfide Bond Formation in RsrA......Page 309
3.3 RsrA Reduction by Thioredoxin......Page 311
4.1 Identification of Yap1p and its Target Genes......Page 312
4.2 Block of Yap1p Nuclear Export by Disulfide Bond Formation......Page 314
4.3 Regulation of Yap1p Activity by Thioredoxin......Page 316
5. Concluding Remarks......Page 317
References......Page 318
1. Summary......Page 324
2. Light Regulated Translation in Chloroplasts: A Case Study of Dynamic Control by Redox Signaling......Page 325
3. The Properties of Light Regulated Redox Signal Transduction and Their Implications......Page 328
4. The Coupling of Regulatory Vicinal Dithiol Sites and Thioredoxins......Page 329
5. Oxidation of the Regulatory VDS in Chloroplasts......Page 331
6. Intracellular Oxidation of Proteins......Page 332
References......Page 334
2. Iron Homeostasis......Page 340
3. Iron Regulatory Proteins and Feedback Regulation of Iron......Page 341
4. Other Targets of Iron Regulatory Proteins......Page 346
5. Regulation of IRE Binding Activity of IRP-1 by Iron......Page 349
7. Do IRP-1 and IRP-2 have Similar or Different Functions?......Page 354
8. Modulation of IRP-1 and IRP-2 by Nitric Oxide......Page 357
9. Activation of IRP-1 by Hydrogen Peroxide......Page 359
10. Regulation of IRP-1 by Hypoxia......Page 360
11. Conclusions......Page 361
References......Page 362
1. Summary......Page 374
2. The Prr System......Page 375
2.1 PrrA......Page 376
2.3 PrrC......Page 378
3. Electron Transport......Page 379
3.1 cbb3 Cytochrome Oxidase......Page 382
4. Redox Control......Page 384
5. Signal Transduction Pathway......Page 387
7. TspO......Page 389
8. Rdx......Page 390
8.1 rdxBHIS......Page 391
8.2 RdxB......Page 393
10. Perspectives......Page 395
Reference......Page 396
1. Summary......Page 406
2. The Permeability Transition......Page 407
2.1 Divalent Cations......Page 408
2.2 CsA and Mitochondrial Cyclophilin......Page 409
2.3 Matrix pH and Pi......Page 410
2.5 Electron Flux at Complex I......Page 411
3. The Pore as a Target of Oxidative Stress......Page 412
4. The Pore as a Source of Oxidative Stress......Page 414
5. Oxidative Stress and Carcinogenesis by 2-Acetylaminofluorene......Page 417
6. Nature of the Permeability Transition......Page 419
7. A Role for the Permeability Transition in Ca+2 Homeostasis?......Page 420
8. The Permeability Transition and Cell Death......Page 421
9. Conclusions......Page 422
References......Page 423
Author Index......Page 434
Subject Index......Page 436