Radicals for Life (eBook)

Cover 1
Table of contents 8
Foreword 6
Part I: Introductory Overview 16
Chapter 1. Nitric oxide radicals and their reactions 18
REFERENCES 28
Part II: DNIC: Physico-chemical Properties and Biological Activity 32
Chapter 2. DNICs: physico-chemical properties and their observations in cells and tissues 34
INTRODUCTION 34
LOW-MOLECULAR-WEIGHT DNIC WITH THIOL-CONTAINING LIGANDS 35
VIBRATION SPECTROSCOPY OF NITROSYL LIGANDS IN DNIC 43
MOSSBAUER (.-RESONANCE) PROPERTIES OF LOW-MOLECULARDNICS WITH THIOL-CONTAINING LIGANDS 46
DNIC WITH SULFIDE AND NEOCUPROINE ANIONIC LIGANDS 49
PROTEIN-BOUND DNICS 52
LABORATORY SYNTHESIS OF DNIC WITH LOW-MOLECULAR ANIONIC LIGANDS 57
THE MECHANISM FOR ASSEMBLY OF DNIC WITH THIOL-CONTAINING LIGANDS 59
STABILITY OF LOW-MOLECULAR-WEIGHT AND PROTEIN-BOUND DNICS IN ANAEROBIC OR AEROBIC SOLUTIONS 62
GEOMETRIC STRUCTURE AND ELECTRONIC CONFIGURATION OF DNIC IN SOLUTION AND CRYSTALLINE STATE 63
OBSERVATIONS OF DNICS IN CELLS AND TISSUES 71
LOOSELY BOUND IRON PARTICIPATES IN THE FORMATION OF DNIC 81
CONCLUDING REMARKS 82
ACKNOWLEDGMENT 82
REFERENCES 82
Chapter 3. Hypotensive, vasodilatory and anti-aggregative properties of dinitrosyl-iron complexes 90
HYPOTENSIVE ACTIVITY OF DNICS 90
THE VASODILATORY ACTIVITY OF DNICS 102
ROLE OF DNIC/ NITRIC OXIDE STORES IN PROTECTION AGAINST NITRIC OXIDE OVERPRODUCTION 105
DNIC CAPACITY OF INHIBITING PLATELET AGGREGATION 107
ACKNOWLEDGMENT 109
REFERENCES 109
Chapter 4. DNICs and intracellular iron: nitrogen monoxide (NO)-mediated iron release from cells is linked to NO-mediated glutathione efflux via MRP1 112
GENERAL INTRODUCTION: NITROGEN MONOXIDE IS A VITAL MESSENGER MOLECULE AND CYTOTOXIC EFFECTOR 112
NITROGEN MONOXIDE FORMS INTRACELLULAR COMPLEXES WITH IRON 112
CELLULAR IRON METABOLISM 113
IRON TRANSPORT AND UPTAKE: TRANSFERRIN AND THE TRANSFERRIN RECEPTOR 1 115
EFFECT OF NITROGEN MONOXIDE ON INTRACELLULAR IRON METABOLISM 115
THE MECHANISM OF NITROGEN MONOXIDE-MEDIATED Fe RELEASE FROM CELLS 117
NITROGEN MONOXIDE MEDIATES IRON EXPORT FROM CELLS BY THE GSH TRANSPORTER, MRP1 120
BIOLOGICAL RELEVANCE OF NITROGEN MONOXIDE-MEDIATED TRANSPORT VIA MRP1 121
CONCLUSIONS 127
ACKNOWLEDGMENTS 127
REFERENCES 128
Chapter 5. Low-molecular dinitrosyl iron complexes can catalyze the degradation of active centers of iron–sulfur proteins 134
ACKNOWLEDGMENT 150
REFERENCES 150
Chapter 6. Products of the reaction of cytosolic and mitochondrial aconitases with nitric oxide 154
ACKNOWLEDGMENT 159
REFERENCES 159
Chapter 7. Harnessing toxic reactions to signal stress: reactions of nitric oxide with iron–sulfur centers and the informative case of SoxR protein 162
INTRODUCTION 162
DNICS AND NITRIC OXIDE TOXICITY 164
SoxR AS A SENSOR OF OXIDATIVE STRESS OR NITRIC OXIDE 164
REPAIR OF PROTEIN DNICs 166
L-CYSTEINE RELEASES FERROUS IRON FROM THE PROTEIN-BOUND DNIC 168
IRON–SULFUR CLUSTERS CAN BE RE-ASSEMBLED TO REPLACE DNIC 168
NEW NITRIC OXIDE SIGNALING PATHWAYS VIA FeS CLUSTERS 170
A MODEL FOR SoxR ACTIVATION IN RESPONSE TO MULTIPLE SIGNALS 170
PERSPECTIVE 171
ACKNOWLEDGMENTS 172
REFERENCES 172
Chapter 8. Nitric oxide and dinitrosyl iron complexes: roles in plant iron sensing and metabolism 176
NITRIC OXIDE FUNCTIONS IN PLANTS 176
NITRIC OXIDE SYNTHESIS IN PLANTS 177
NITRIC OXIDE STORAGE, DELIVERY AND DETOXIFICATION IN PLANTS 177
DNICS IN PLANTS 178
PLANT IRON NUTRITION: AN OVERVIEW 179
NITRIC OXIDE AND DNICS PARTICIPATION IN PLANT IRON METABOLISM 180
PERSPECTIVES 181
ACKNOWLEDGMENTS 182
REFERENCES 182
Part III: Nitrosospecies and S-nitrosothiols: Physico-chemical Properties and Biological Activity 186
Chapter 9. Low-molecular-weight S-nitrosothiols 188
SPECTROSCOPIC PROPERTIES 190
SYNTHESIS AND DETECTION IN VITRO AND IN VIVO 190
STABILITY OF GSNO IN VITRO 194
STABILITY OF RSNO IN VIVO 199
TRANSPORT OF LMW S-NITROSOTHIOLS 201
BIOLOGICAL ACTIONS OF LMW NITROSOTHIOLS 202
THERAPEUTIC USES OF LMW NITROSOTHIOLS 206
REFERENCES 208
Chapter 10. S-nitrosated proteins: formation, metabolism, and function 216
INTRODUCTION 216
BIOLOGICAL CHEMISTRY 216
DETECTION 220
PROTEOMICS 222
FUNCTION OF S-NITROSOTHIOLS 223
CONCLUSIONS 226
ACKNOWLEDGMENTS 227
REFERENCES 227
Chapter 11. Chemical equilibria between S-nitrosothiols and dinitrosyl iron complexes with thiol-containing ligands 238
INTRODUCTION 238
THE REDOX REACTIONS OF COPPER 239
DECOMPOSITION AND SYNTHESIS OF S-NITROSOTHIOLS BY IRON 240
THE EXPERIMENTS WITH NEOCUPROINE SHOW THAT DECOMPOSITION AND SYNTHESIS OF RS-NO ARE CATALYZED BY COPPER AS WELL AS IRON 241
THE MECHANISM OF CATALYTIC DECOMPOSITION OF RS-NO BY FERROUS IRON 246
THE MECHANISM OF RS-NO SYNTHESIS CATALYZED BY IRON 255
THE EQUILIBRIA BETWEEN THIOL-DNIC AND RS-NO 260
NITROSOTHIOLS ARE NITRIC OXIDE DONORS THROUGH THEIR TRANSFORMATION INTO DNICS 262
ACKNOWLEDGMENT 265
REFERENCES 266
Chapter 12. Cellular non-heme iron modulates apoptosis and caspase 3 activity 268
INTRODUCTION 268
SUMMARY OF OBSERVATIONS 269
MECHANISTIC CONSIDERATIONS 270
CONCLUSIONS 277
REFERENCES 278
Chapter 13. Nitrite and nitrosospecies in blood and tissue: approaching the gap between bench and bedside 284
NITRIC OXIDE AND RED BLOOD CELLS 285
RBC: A NOVEL SOURCE FOR NITRIC OXIDE 286
NITRIC OXIDE AND PLASMA 287
NITROSOSPECIES OTHER THAN RSNOS IN PLASMA 288
NITRIC OXIDE SOLUTIONS 288
NITRIC OXIDE CAN BE TRANSPORTED IN ITS FREE FORM ALONG THE VASCULAR TREE 289
PLASMA RSNOS AS POTENTIAL DISEASE MARKERS 289
ANALYSIS OF NITRIC OXIDE SPECIES: FINDING THE RIGHT APPROACH 290
ANALYSIS OF NITRIC OXIDE SPECIES: FINDING THE RIGHT APPROACH 290
PLASMA NITROSOSPECIES AND CARDIOVASCULAR DISEASE 291
EFFECTS OF NITRIC OXIDE AND RSNOS ON LEFT VENTRICULAR FUNCTION 292
PLASMA NITRITE AND ENOS-ACTIVITY 292
ORIGIN OF PLASMA NITRITE 295
NITRITE SIGNALING 295
NITRITE AND DIAGNOSTICS 296
TISSUE STORES OF NITRIC OXIDE 296
SUMMARY 297
REFERENCES 297
Part IV: Nitrites and Nitrates as a NO Source in Cells and Tissues 304
Chapter 14. Nitrite as endothelial NO donor under anoxia 306
AQUEOUS REDUCTION PATHWAYS OF NITRITE 309
IN VITRO EXPERIMENTS ON eNOS IN BUFFERED SOLUTION 310
EXPERIMENTS ON ENDOTHELIAL CELL CULTURES 313
MECHANISTIC HYPOTHESIS 317
NITRIC OXIDE IS RELEASED FROM FULL-LENGTH eNOS BUT NOT FROM nNOS UNDER ANOXIA 319
COMPARISON OF THE RATES OF NITRIC OXIDE GEMINATE RECOMBINATION TO THE HEME OF eNOS AND OF nNOS 321
IMPLICATIONS FOR HUMAN PHYSIOLOGY 323
REFERENCES 324
Chapter 15. Nitrite as NO donor in cells and tissues 328
INTRODUCTION 328
XANTHINE OXIDASE-CATALYZED NITRITE REDUCTION 329
EFFECT OF OXYGEN ON XO-MEDIATED NITRIC OXIDE GENERATION FROM NITRITE [2] 334
MEASUREMENT OF NITRIC OXIDE FORMATION IN ISCHEMIC MYOCARDIUM [6,7,54] 338
EVALUATION OF THE ROLE OF NITRITE-DERIVED NITRIC OXIDE IN POSTISCHEMIC INJURY 341
NITROSYL-HEME FORMATION AND NITRIC OXIDE SIGNALING DURING BRIEF MYOCARDIAL ISCHEMIA 342
CONCLUSION 346
REFERENCES 346
Chapter 16. The anti-microbial and cytotoxic actions of nitrite, and the use of DNIC as a marker for these actions 352
INTRODUCTION 352
THE ANTI-MICROBIAL AND CYTOTOXIC ACTIVITIES OF NITRITE 353
DNIC MAY BE USED AS A BIOMARKER FOR THE ANTI-MICROBIAL AND CYTOTOXIC ACTIONS OF NITRITE 356
CONCLUDING REMARKS 357
ACKNOWLEDGMENTS 358
REFERENCES 358
Chapter 17. Organic nitrates and nitrites as stores of NO bioactivity 362
INTRODUCTION 362
NITRATE THERAPEUTICS 363
NITRITE THERAPEUTICS 366
NITRATES AS NITRIC OXIDE MIMETICS 366
ENDOGENOUS NITRATES AND NITRITES 370
CHEMICAL REACTIVITY OF NITRATES 371
CHEMICAL REACTIVITY OF NITRITES 373
BIOLOGICAL REACTIVITY OF NITRATES AND BIOACTIVATION 374
PATHWAYS FOR REDUCTION TO NITRIC OXIDE 376
PROTEIN MEDIATORS OF BIOTRANSFORMATION 379
NITRATE TOLERANCE 383
SUMMARY 384
REFERENCES 384
Part V: Dithiocarbamate Iron Complexes: Implication for NO Studies 396
Chapter 18. Mononitrosyl-iron complexes with dithiocarbamate ligands: physico-chemical properties 398
INTRODUCTION 398
LIGAND STRUCTURE OF IRON–DITHIOCARBAMATE COMPLEXES 400
TRAPPING OF FREE NITRIC OXIDE BY IRON–DITHIOCARBAMATE COMPLEXES 400
SPECTROSCOPIC PROPERTIES OF (NITROSYLATED) IRON–DITHIOCARBAMATE COMPLEXES 404
ISOTOPIC SUBSTITUTIONS AFFECT THE EPR LINESHAPES OF THE MNIC ADDUCTS 406
THE DETERMINANTS OF MNIC FORMATION IN TISSUES: REDOX STATE AND LIGANDS OF IRON 407
REDUCTION WITH DITHIONITE ENHANCES MNIC YIELDS IN VIVO 409
OTHER EFFECTS OF REDUCTION ON EPR SPECTRA 411
PREVENTION OF REDUCTION OF ENDOGENOUS NITRITE BY BUFFERING 412
DIFFERENT LIGANDS COMPETE WITH DETC FOR EXOGENOUS IRON IN TISSUES 414
DIFFERENT LIGANDS COMPETE WITH DETC FOR EXOGENOUS IRON IN CULTURED ENDOTHELIAL CELLS 414
LOOSELY BOUND IRON PARTICIPATES IN THE REDOX EQUILIBRIUM 415
ENDOGENOUS COMPOUNDS AS IMPOSTORS FOR TRUE NITRIC OXIDE 416
THE MEANING OF THE FERRIC HIGH-SPIN SIGNAL AT g = 4.3 417
CONCLUDING REMARKS 417
REFERENCES 418
Chapter 19. Protection against allograft rejection by iron–dithiocarbamate complexes 422
INTRODUCTION 422
ROLE OF INOS IN CARDIAC REJECTION: EVIDENCE FROM PHARMACOLOGICAL APPROACHES 422
ROLE OF INOS IN CARDIAC REJECTION: EVIDENCE FROM GENE DELETION STRATEGIES 424
EFFECTS OF IRON–DITHIOCARBAMATES ON GRAFT SURVIVAL AND REJECTION 424
EVIDENCE THAT IRON–DITHIOCARBAMATES ACT IN VIVO TO SCAVENGE NITRIC OXIDE 425
IRON–DITHIOCARBAMATES FOR QUANTIFYING NITRIC OXIDE LEVELS 429
EFFECT OF IRON–DITHIOCARBAMATES TO INHIBIT TARGETS OF NITRIC OXIDE 429
ANTI-INFLAMMATORY ACTIONS OF DITHIOCARBAMATES 432
EFFECTS ON LYMPHOCYTE ACTIVATION AND PROLIFERATION 432
THE ROLE OF NITRIC OXIDE IN LYMPHOCYTE PROLIFERATION 433
OTHER ACTIONS OF IRON–DITHIOCARBAMATES INVOLVING IMMUNOSUPPRESSION 433
CONCLUSION 434
ACKNOWLEDGMENTS 434
REFERENCES 434
INDEX 438