Current Topics in Cellular Regulation (eBook)

Front Cover 1
Current Topics in Cellular Regulation 4
Copyright Page 5
Contents 6
Chapter 1. Cellular Thiols and Redox-Regulated Signal Transduction 12
I. Biological Thiols 12
II. Thioredoxin and Glutathione Systems 13
III. Protein Phosphorylation 17
IV. Protein-DNA Interaction 22
V. Cell Calcium 27
VI. Manipulation of Cell Redox 31
VII. Summary and Conclusions 35
References 37
Chapter 2. Integration of Antagonistic Signals in the Regulation of Nitrogen Assimilation in Escherichia coli 42
I. The Physiological Response to Nitrogen Limitation 43
II. What Are the Signals? 49
III. Signal Transduction System Regulating Glutamine Synthetese Activity and the Transcription of Nitrogen-Regulated Genes 52
IV . Structure-Function Analysis of the PII Protein 63
V. Kinetic Analysis of Utase and UR Activities and Their Regulation 71
VI. Reconstitution of the UTase/UR-PII Monocycle 74
VII. Reconstitution of the Bicyclic Cascade Regulating the Phosphorylation of NRI 74
VIII. Reconstitution of the GS-ATase-UTaseNR-PI1 Bicyclic Cascade 78
IX. Comparison of the Regulation of Glutamine Synthetase Adenylylation State with Regulation of NRI Phosphorylation State in the Reconstituted Bicyclic Systems 80
X. A Hypothesis for the Antagonistic Regulation by Signals of Carbon and Nitrogen Status 82
References 83
Chapter 3. Regulation of Nuclear Import and Export 88
I. Introduction 88
II. The Nuclear Pore: An Asymmetric Structure Mediating Transport 89
III. Nuclear Protein Import 91
IV. Nuclear Protein Export 98
V. Independent Regulation of Nuclear Import and Export 102
References 104
Chapter 4. Regulation of Glutathione Synthesis 106
I. Functions and Importance of GSH 106
II. Antioxidant Function of GSH 107
III. GSH as Cysteine Storage and the .-Glutamyl Cycle 107
IV. Synthesis of Hepatic GSH 109
V. Factors That Determine the Availability of Cysteine 111
VI. Regulation of GCS 117
References 124
Chapter 5. Superoxide Dismutase, Oxidative Stress, and Cell Metabolism 128
I. Definition of Oxidative Stress 128
II. Antioxidant Defense Systems 128
III. The Family of Superoxide Dismutases 129
IV. Loss of Superoxide Dismutase Function and Oxidative Stress 130
V. Superoxide Dismutase and Amino Acid Metabolism 131
VI. Superoxide Dismutase and Sugar Metabolism 134
VII. Superoxide Dismutase and Metal Metabolism 134
VIII. Conclusions 139
References 140
Chapter 6. Regulation of Axonal Neurofilament Phosphorylation 144
I . Kinase Phosphorylating Neurofilaments 146
References 158
Chapter 7. Thiol-Based Antioxidants 162
I. Thiols as Cell Redox Buffers 162
II. Compartmentalization of Cell Thiols 163
III. The Central Role of Glutathione in Cell Redox Reactions 166
IV. Regulation of GSH Synthesis 168
V. Oxidant-Induced Increases in Cellular GSH Levels 171
VI. Metallothioneins as Antioxidants 171
VII. Lipoic Acid as a Thiol Antioxidant 173
VIII. Thioredoxin as an Antioxidant 174
IX. Thiyl Radicals and a Thiol-Specific Antioxidant Protein 175
X. Thiols as Modifiers of Protein Activity 176
XI.Thiols as Regulators of Gene Activation 178
XII. Effects of Thiol Supplementation on Tissue Thiol Levels in Vivo 180
XIII. Clinical Uses of Thiol Antioxidants 184
XIV. Summary and Conclusions 185
References 186
Chapter 8. Regulation and Role of Heme Oxygenase in Oxidative Injury 192
I . Introduction 192
II. Biochemistry and Physiology of Heme Oxygenase 192
III. Tissue Specificity and Localization of HO Isoenzymes 193
IV. Organization and Regulation of HO Genes 195
V. Regulation of HO in Oxidant Stress and Inflammation 197
VI. Developmental Regulation of Heme Oxygenase 200
VII . Role of Heme Oxygenase in Oxidative Stess 202
VIII . Role of HO in Oxidant Stress and Inflammation 206
IX . Summary 207
References 208
Chapter 9. Antioxidant Regulation of Genes Encoding Enzymes That Detoxify Xenobiotics and Carcinogens 212
I. Antioxidants and Their Mode of Action 212
II. Induction of Genes Encoding Enzymes That Detoxify Xenobiotics and Carcinogens 214
III. Antioxidant Response Element 215
IV. Antioxidant Response Element-Binding Proteins 216
V. Mechanism of Signal Transduction 220
VI. Summary and Conclusions 222
References 224
Chapter 10. Modulation of Vascular Cell Activation, Function, and Apoptosis: Role of Antioxidants and Nuclear Factor-KB 228
I. Involvement of Multiple Radical Generating Systems in Nuclear Factor-kB Mobilization and Adhesion Molecule Induction by Cytokines in Endothelial Cells 228
II. Selective Suppression of Endothelial VCAM-1 Expression, Monocyte Adhesion, and NF-KB Mobilization by Lipid-Soluble a-Tocopheryl Succinate 232
III. Effects of Antioxidants in Monocyte Adhesiveness in Smokers 235
IV. Mechanisms of T-cell Apoptosis Induced by Tocopherol Succinate 237
V. Density-Dependent Induction of Smooth Muscle Cell Apoptosis by Pyrrolidine Dithiocarbomate (PDTC): A Role of NF-kB in Regulating Components of the Antiapoptotic Machinery 238
VI. Summary and Conclusions 242
References 242
Chapter 11. Calcineurin: From Structure to Function 248
I. Introduction 248
II. Biochemical and Structural Properties 249
III. Roles of Calcineurin in Fungi and Plants 261
IV. Regulation of NFAT Transcription Factors by Calcineurin 268
V. Other Transcription Factors Regulated by Calcineurin 279
VI. Role of Calcineurin in Neuronal Function 283
VII . FKBP-Mediated Regulation of Ca2+ Channels by Calcineurin 288
VIII . Natural Inhibitors of Calcineurin 288
XI. Summary and Perspectives 293
References 294
Index 308
Color Plate Section 330