Ignarro Nitric Oxide

Biology and Pathobiology
2. Auflage 2009
ISBN: 978-0-08-092044-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 845 Seiten

Nitric oxide (NO) is a gas naturally found in the body that conveys information between cells. In the last decade researchers have found that NO is a signaling molecule of key importance for the cardiovascular system, regulating blood pressure and blood flow to different organs. In addition, discoveries surrounding nitric oxide's role as a principal neurotransmitter moderating erectile function, a pathophysiological negotiator and messenger in inflammation, and a weapon against infections have increased research attention across the fields of biochemistry, chemistry, molecular biology, gene therapy, cell biology, immunology, pharmacology, neuroscience, and physiology.
Edited by Nobel Laureate Louis J. Ignarro Up-to-date therapeutic implications of nitric oxide researchAuthored by world experts on nitric oxide Detailed research of the biochemistry and synthesis of nitric oxide

Autoren/Hrsg.

Ignarro, Louis J.

Inhaltsverzeichnis

1;Front Cover;1
2;Nitric Oxide: Biology and Pathobiology;4
3;Copyright Page;5
4;Contents;6
5;Section I. Chemical Biology;8
5.1;Chapter 1 Determinants of Nitric Oxide Chemistry: Impact of Cell Signaling Processes;10
5.1.1;ABSTRACT;10
5.1.2;INTRODUCTION;10
5.1.3;CONTEXT DEPENDENCE OF NO RESPONSE;12
5.1.4;CELLULAR MILIEU AND NO REDOX CHEMISTRY;13
5.1.5;CONCENTRATION RANGE OF ENDOGENOUSLY GENERATED NO;14
5.1.6;KINETIC DETERMINANTS FOR MOLECULAR TARGET INTERACTIONS;18
5.1.7;CONCLUSION;25
5.1.8;REFERENCES;25
5.2;Chapter 2 Nitric Oxide Redox Biochemistry in Lipid Environments;34
5.2.1;SUMMARY;34
5.2.2;CHEMISTRY OF NITRIC OXIDE AND REACTIVE NITROGEN SPECIES;34
5.2.3;PHYSICAL INTERACTIONS OF NITRIC OXIDE AND REACTIVE NITROGEN SPECIES WITH LIPID MEMBRANES AND LIPOPROTEINS;36
5.2.4;REACTIONS OF REACTIVE NITROGEN SPECIES IN LIPID MILIEU;41
5.2.5;LIPID NITRATION AND ITS ROLE IN INFLAMMATION;51
5.2.6;CONCLUDING REMARKS;55
5.2.7;ACKNOWLEDGMENTS;56
5.2.8;REFERENCES;56
5.3;Chapter 3 Mechanisms and Biological Consequences of Peroxynitrite-Dependent Protein Oxidation and Nitration;68
5.3.1;SUMMARY;68
5.3.2;OVERVIEW OF PEROXYNITRITE BIOCHEMISTRY;69
5.3.3;PEROXYNITRITE-MEDIATED AMINO ACID AND PROTEIN MODIFICATIONS;70
5.3.4;BIOLOGICAL CONSEQUENCES OF PEROXYNITRITE-MEDIATED PROTEIN OXIDATION AND NITRATION;89
5.3.5;CONCLUSIONS;93
5.3.6;ACKNOWLEDGMENTS;93
5.3.7;REFERENCES;93
5.4;Chapter 4 Systems Approaches to Unraveling Nitric Oxide Response Networks in Prokaryotes;110
5.4.1;SUMMARY;110
5.4.2;INTRODUCTION;110
5.4.3;BIOLOGICAL CIRCUITS;111
5.4.4;RNS PRODUCTION AND INTERACTION WITH PROKARYOTES;112
5.4.5;RNS RESPONSE ELEMENTS;113
5.4.6;GLOBAL RNS RESPONSE;120
5.4.7;CLOSING REMARKS;131
5.4.8;REFERENCES;132
6;Section II. Principles of Biology;144
6.1;Chapter 5 Uncoupling of Endothelial Nitric Oxide Synthase in Cardiovascular Disease and its Pharmacological Reversal;146
6.1.1;SUMMARY;146
6.1.2;INTRODUCTION;147
6.1.3;NORMAL ENZYMATIC FUNCTION OF ENDOTHELIAL NO SYNTHASE ([sub(E)]NOS);147
6.1.4;PHYSIOLOGIC REGULATION OF [sub(E)]NOS ACTIVITY;149
6.1.5;OXIDATIVE STRESS IN VASCULAR DISEASE REDUCES THE BIOAVAILABILITY OF VASCULAR NO;150
6.1.6;CARDIOVASCULAR RISK FACTORS AND VASCULAR DISEASE ARE ASSOCIATED WITH AN INCREASED PRODUCTION OF ROS IN THE VASCULAR WALL;150
6.1.7;ANTIOXIDANT ENZYMES POTENTIALLY PROTECTING AGAINST VASCULAR OXIDATIVE STRESS;154
6.1.8;MOLECULAR MECHANISMS CONTRIBUTING TO REDUCED LEVELS OF BIOACTIVE NO IN VASCULAR DISEASE;156
6.1.9;MOLECULAR MECHANISMS TRIGGERING [sub(E)]NOS UNCOUPLING;156
6.1.10;VASCULAR OXIDATIVE STRESS AND ENDOTHELIAL DYSFUNCTION PREDISPOSE TO ATHEROSCLEROSIS;159
6.1.11;PHARMACOLOGICAL APPROACHES TO REDUCE OXIDATIVE STRESS AND PREVENT OR REVERSE [sub(E)]NOS UNCOUPLING;159
6.1.12;CONCLUSIONS;161
6.1.13;REFERENCES;162
6.2;Chapter 6 Tetrahydrobiopterin: An Essential Cofactor for Nitric Oxide Synthases and Amino Acid Hydroxylases;176
6.2.1;SUMMARY;176
6.2.2;FROM THE WINGS OF BUTTERFLIES TO HYDROXYLATING COFACTOR: DISCOVERY OF PTERINS;176
6.2.3;BH[sub(4)] IS AN ESSENTIAL COFACTOR FOR AAAHS AND NOSs;178
6.2.4;BH[sub(4)] REDOX PROPERTIES AND REGENERATION BY SALVAGE AND RECYCLING PATHWAYS;185
6.2.5;DE NOVO BIOSYNTHESIS OF BH[sub(4)];186
6.2.6;ANATOMICAL AND SUBCELLULAR LOCALIZATION OF GTPCH;191
6.2.7;REGULATION OF GTPCH ACTIVITY;191
6.2.8;GENETIC DISEASES MEDIATED BY BH[sub(4)] DEFICIENCY;197
6.2.9;MOUSE MODELS OF BH[sub(4)] DEFICIENCY;200
6.2.10;ACKNOWLEDGMENT;201
6.2.11;REFERENCES;201
6.3;Chapter 7 Regulation of the Expression of Inducible Nitric Oxide Synthase;218
6.3.1;SUMMARY;218
6.3.2;INTRODUCTION;218
6.3.3;STRUCTURE OF THE HUMAN iNOS GENE;219
6.3.4;REGULATION OF iNOS ACTIVITY;220
6.3.5;EXPRESSIONAL REGULATION OF iNOS;220
6.3.6;CONCLUSIONS;248
6.3.7;REFERENCES;249
6.4;Chapter 8 Molecular Regulation of Inducible Nitric Oxide Synthase;276
6.4.1;INTRODUCTION;276
6.4.2;CLONING OF THE MURINE AND HUMAN INOS GENES;277
6.4.3;ANALYSIS OF THE MURINE AND HUMAN INOS PROMOTERS;278
6.4.4;A CENTRAL ROLE FOR THE NF-?B SIGNALING PATHWAY IN INOS EXPRESSION;279
6.4.5;THE IFN/JAK/STAT PATHWAY CONTRIBUTES TO INOS INDUCTION;280
6.4.6;CYTOKINE SYNERGY REGULATES INOS TRANSCRIPTION;282
6.4.7;MAPK SIGNALING AND INOS;284
6.4.8;PI3K AND AKT SIGNALING EFFECTS ON INOS;284
6.4.9;AP-1 SIGNALING AND INOS TRANSCRIPTION;285
6.4.10;OCT-1 ALSO EXERTS EFFECTS ON INOS TRANSCRIPTION;285
6.4.11;EFFECTS OF CAMP, C/EBP, AND CAMP-RESPONSIVE ELEMENT BINDING PROTEIN (CREB) ON INOS EXPRESSION;286
6.4.12;iNOS IS A TARGET OF THE WNT/ß-CATENIN SIGNALING PATHWAY;287
6.4.13;EPIGENETIC REGULATION OF THE HUMAN INOS GENE;288
6.4.14;POST-TRANSCRIPTIONAL REGULATION OF INOS EXPRESSION;289
6.4.15;AGENTS THAT DOWN-REGULATE INOS EXPRESSION;291
6.4.16;iNOS EXPRESSION IS NEGATIVELY REGULATED BY NO;293
6.4.17;SUMMARY;294
6.4.18;REFERENCES;294
6.5;Chapter 9 Soluble Guanylate Cyclase: Allosteric Activation and Redox Regulation;308
6.5.1;SUMMARY;308
6.5.2;INTRODUCTION;308
6.5.3;PHYSIOLOGICAL ROLES AND PATHOLOGICAL DYSFUNCTION;309
6.5.4;ENZYME STRUCTURE;309
6.5.5;SUBCELLULAR LOCALIZATION;311
6.5.6;TRANSCRIPTIONAL AND POST-TRANSLATIONAL REGULATION;311
6.5.7;ISSUES WITH THE THERAPEUTIC USE OF NO DONORS AS SGC ACTIVATORS;312
6.5.8;ALLOSTERIC SGC STIMULATION: NO-INDEPENDENT, HEME-DEPENDENT STIMULATORS;312
6.5.9;ALLOSTERIC SGC ACTIVATION: NO-INDEPENDENT, HEME-INDEPENDENT ACTIVATORS;315
6.5.10;THERAPEUTIC POTENTIAL OF ALLOSTERIC SGC 'STIMULATORS' AND 'ACTIVATORS' (I.E. SGC AGONISTS);316
6.5.11;CLINICAL TRIALS OF SGC AGONISTS;318
6.5.12;REDOX REGULATION: THIOL-BASED MODULATION;319
6.5.13;REDOX REGULATION: HEME FUNCTIONALITY;320
6.5.14;FUTURE DIRECTION;320
6.5.15;REFERENCES;321
6.6;Chapter 10 Untargeted Discovery of Nitric Oxide-Modified Proteins;334
6.6.1;SUMMARY;334
6.6.2;DISCOVERY-BASED APPROACHES FOR IDENTIFYING NO-DEPENDENT PROTEIN MODIFICATIONS;334
6.6.3;PROTEIN S-NITROSYLATION;335
6.6.4;TYROSINE NITRATION;364
6.6.5;THE FUTURE OF PROTEOMIC STUDIES AND NO;390
6.6.6;ACKNOWLEDGMENTS;391
6.6.7;REFERENCES;391
6.7;Chapter 11 Fatty Acid Transduction of Nitric Oxide Signaling: Cyclooxygenases, Lipoxygenases and Nitro-Fatty Acids;398
6.7.1;SUMMARY;398
6.7.2;INTRODUCTION;399
6.7.3;NO REACTIONS IN LIPOPHILIC MILIEU;399
6.7.4;NO MODULATES ENZYMATIC LIPID OXIDATION;401
6.7.5;FATTY ACID NITRATION PRODUCTS ARISING FROM NO-DERIVED SPECIES;404
6.7.6;MECHANISMS OF NO[sub(2)]-FA-MEDIATED CELL SIGNALING;406
6.7.7;SUMMARY;410
6.7.8;REFERENCES;410
6.8;Chapter 12 Nitric Oxide Signaling in Vascular Cells is Regulated through CD47 by Thrombospondin-1;422
6.8.1;ABSTRACT;422
6.8.2;INTRODUCTION;423
6.8.3;NITRIC OXIDE;423
6.8.4;THROMBOSPONDIN-1;424
6.8.5;INHIBITION OF NO SIGNALING BY TSP1;426
6.8.6;CD47 MEDIATES INHIBITION OF NO/CGMP SIGNALING;428
6.8.7;INHIBITION OF NO/CGMP SIGNALING VIA CD36;428
6.8.8;TSP1 REGULATION OF NO SIGNALING IN PLATELETS;429
6.8.9;TSP1 AND WOUND HEALING;430
6.8.10;TSP1 MODULATES TISSUE BLOOD FLOW AND SURVIVAL UNDER VASOACTIVE AND ISCHEMIC STRESS;431
6.8.11;TSP1 AND DECREASED BLOOD FLOW IN AGING;433
6.8.12;TSP1 LIMITS TISSUE SURVIVAL TO ISCHEMIA-REPERFUSION INJURY;433
6.8.13;TARGETING TSP1 OR CD47 INCREASES TISSUE BLOOD FLOW AND SURVIVAL AFTER ISCHEMIA AND I/R INJURY;435
6.8.14;FUTURE DIRECTIONS;435
6.8.15;REFERENCES;437
6.9;Chapter 13 The Regulation of Cell Energetics and Mitochondrial Signaling by Nitric Oxide;448
6.9.1;SUMMARY;448
6.9.2;INTRODUCTION: MITOCHONDRIAL FUNCTION AND ITS REGULATION;449
6.9.3;REGULATION OF CYTOCHROME OXIDASE ACTIVITY AND MITOCHONDRIAL OXYGEN UPTAKE BY NO: O[sub(2)]/NO COMPETITION;450
6.9.4;SOURCES OF MITOCHONDRIAL NITRIC OXIDE;453
6.9.5;mtNOS: ACTIVITY, EXPRESSION AND INTERNALIZATION;453
6.9.6;THE REDUCTION OF NITRITE;457
6.9.7;THE MITOCHONDRIAL PRODUCTION OF SUPEROXIDE RADICAL AND OF HYDROGEN PEROXIDE;457
6.9.8;THE MITOCHONDRIAL PRODUCTION OF SUPEROXIDE RADICAL IS HIGHLY STIMULATED BY NO;458
6.9.9;MITOCHONDRIAL NO UTILIZATION;460
6.9.10;UBIQUINONE SUPPLEMENTATION: SOD PRODUCTION, NO DECAY AND REVERSION OF CYTOCHROME OXIDASE INHIBITION;460
6.9.11;PEROXYNITRITE-DEPENDENT PRODUCTION OF SOD;461
6.9.12;THE INTEGRAL MITOCHONDRIAL METABOLISM OF O[sub(2)], NO AND SOD;462
6.9.13;NO AND H[sub(2)]O[sub(2)] IN CELL FATE: MITOCHONDRIAL SIGNALING IN CELL PROLIFERATION, ARREST AND APOPTOSIS;465
6.9.14;THE REGULATION OF CELL ENERGETICS THROUGH MITOCHONDRIAL POPULATION;468
6.9.15;THE APPLIED PHYSIOLOGY OF MITOCHONDRIAL NO;469
6.9.16;NO, MITOCHONDRIA AND ENDOCRINE REGULATION;471
6.9.17;MITOCHONDRIAL NO CONCENTRATIONS AND MECHANISMS OF DISEASE;472
6.9.18;CONCLUDING REMARKS;476
6.9.19;ACKNOWLEDGMENTS;478
6.9.20;REFERENCES;478
6.10;Chapter 14 Nitric Oxide – Asymmetric Dimethylarginine System in Endothelial Cell Senescence;490
6.10.1;SUMMARY;490
6.10.2;INTRODUCTION;490
6.10.3;BIOMARKERS OF CELLULAR SENESCENCE;491
6.10.4;NO-ADMA SYSTEM IN ENDOTHELIAL CELL SENESCENCE;494
6.10.5;MODULATION OF NO-ADMA SYSTEM CONTRIBUTES TO DELAY OR ACCELERATION OF THE PROCESS OF HUMAN ENDOTHELIAL CELL SENESCENCE;501
6.10.6;CONCLUSIONS;506
6.10.7;REFERENCES;506
6.11;Chapter 15 The Role of Nitric Oxide in Apoptosis and Autophagy: Biochemical and Computational Studies;520
6.11.1;SUMMARY;520
6.11.2;INTRODUCTION;521
6.11.3;EFFECTS OF NO ON APOPTOSIS;522
6.11.4;NITRIC OXIDE MODULATES CELL DEATH-RELATED GENES;528
6.11.5;DECODING THE COMPLEX ROLES OF NO IN APOPTOSIS USING COMPUTATIONAL SIMULATIONS;531
6.11.6;CONCLUSION/NO APOPTOSIS AND AUTOPHAGY FUTURE MODELING;534
6.11.7;ACKNOWLEDGMENTS;534
6.11.8;REFERENCES;534
6.12;Chapter 16 Nitric Oxide Formation from Inorganic Nitrate and Nitrite;546
6.12.1;SUMMARY;546
6.12.2;INTRODUCTION;546
6.12.3;SOURCES OF NITRATE AND NITRITE;547
6.12.4;THE ENTEROSALIVARY CIRCULATION OF NITRATE;547
6.12.5;DIETARY NITRATE AND GASTRIC CANCER;548
6.12.6;INTRAGASTRIC GENERATION OF NITRIC OXIDE;549
6.12.7;INTERACTIONS BETWEEN NITRITE AND OTHER DIETARY COMPOUNDS;550
6.12.8;SYSTEMIC NO GENERATION FROM NITRITE;552
6.12.9;NITRITE AS A VASODILATOR;552
6.12.10;MECHANISMS FOR NITRITE REDUCTION;552
6.12.11;BIOACTIVATION OF INORGANIC NITRATE;553
6.12.12;DIETARY NITRATE AND NITRITE AND CARDIOVASCULAR FUNCTION;554
6.12.13;REFERENCES;555
6.13;Chapter 17 Mechanisms of Nitrite Reduction in Ischemia in the Cardiovascular System;562
6.13.1;SUMMARY;562
6.13.2;INTRODUCTION;562
6.13.3;SOURCE AND STORAGE OF ENDOGENOUS NITRITE;563
6.13.4;BIOLOGICAL ACTIVITY OF NITRITE: DEPENDENCY ON OXYGEN AND REDUCTION TO NO;566
6.13.5;EFFECTS OF NITRITE IN I/R INJURY;569
6.13.6;NON-ENZYMATIC CONVERSION OF NITRITE TO NO;572
6.13.7;ENZYMATIC CONVERSION OF NITRITE TO NO;573
6.13.8;THERAPEUTIC POTENTIAL OF NITRITE;581
6.13.9;REFERENCES;581
6.14;Chapter 18 Nitrite Therapy for Ischemic Syndromes;594
6.14.1;ABSTRACT;594
6.14.2;INTRODUCTION;595
6.14.3;NO AND PROTECTION AGAINST ISCHEMIA;595
6.14.4;NITRITE AND PROTECTION AGAINST ISCHEMIA/REPERFUSION INJURY;597
6.14.5;NITRITE AND THERAPEUTIC ANGIOGENESIS;601
6.14.6;FUTURE RESEARCH CONSIDERATIONS;602
6.14.7;CLINICAL TRANSLATION OF NITRITE THERAPY TO ISCHEMIC DISEASES;603
6.14.8;SUMMARY;605
6.14.9;CONFLICT OF INTEREST;606
6.14.10;REFERENCES;606
6.15;Chapter 19 Nitrite and Heme Globins: Reaction Mechanisms and Physiological Targets;612
6.15.1;SUMMARY;612
6.15.2;INTRODUCTION;612
6.15.3;SOURCES OF NITRITE IN VIVO;613
6.15.4;NITRITE AND HEME GLOBINS: A LONG HISTORY;613
6.15.5;NITRITE: A PHYSIOLOGICAL VASODILATOR OR INERT METABOLITE?;615
6.15.6;HEMOGLOBIN AND NITRITE: OLD CHEMISTRY REVISITED;615
6.15.7;ESCAPING HEME SCAVENGING: REDUCTIVE ANHYDRASE CHEMISTRY;618
6.15.8;OTHER REACTION PATHWAYS TO N[sub(2)]O[sub(3)] FORMATION;620
6.15.9;EXPANDING THE PARADIGM: MYOGLOBIN AS A TISSUE NITRITE REDUCTASE;620
6.15.10;NITRITE MEDIATES CYTOPROTECTION AFTER CARDIAC ISCHEMIA/REPERFUSION;622
6.15.11;MECHANISMS OF CYTOPROTECTION: MITOCHONDRIA AS A TARGET OF THE NITRITE–MYOGLOBIN REACTION;624
6.15.12;S-NITROSATION OF MITOCHONDRIAL COMPLEX I AND CYTOPROTECTION AFTER ISCHEMIA/REPERFUSION;626
6.15.13;NEUROGLOBIN AS A NITRITE REDUCTASE;627
6.15.14;CONCLUSION;627
6.15.15;REFERENCES;627
7;Section III. Principles of Pathobiology;634
7.1;Chapter 20 Nitric Oxide in Vascular Damage and Regeneration;636
7.1.1;SUMMARY;636
7.1.2;NITRIC OXIDE SIGNALING IN THE ARTERY WALL;636
7.1.3;NO IN VASCULAR DYSFUNCTION;639
7.1.4;NO AND RENOVASCULAR DISEASE;640
7.1.5;CLINICAL MEASUREMENTS OF ENDOTHELIAL FUNCTION;644
7.1.6;NOS COMPETITIVE INHIBITORS AND ATHEROSCLEROSIS;646
7.1.7;NOS KNOCKOUT MICE IN THE PATHOBIOLOGY OF NO AND ATHEROSCLEROSIS;647
7.1.8;NO AND OXIDATION-SENSITIVE MECHANISMS;649
7.1.9;ENOS POLYMORPHISMS;651
7.1.10;MOLECULAR MECHANISMS REGULATING ENOS;652
7.1.11;NO AND POLYPHENOLS;654
7.1.12;NO AND VASCULAR REGENERATION;656
7.1.13;CONCLUSIONS AND ROAD AHEAD;662
7.1.14;ACKNOWLEDGMENTS;662
7.1.15;REFERENCES;662
7.2;Chapter 21 Free Radicals as Atherosclerotic Risk in Relation to Nitric Oxide;680
7.2.1;ABSTRACT;680
7.2.2;ATHEROSCLEROSIS AND FREE RADICALS;680
7.2.3;FREE RADICALS AND THROMBOSIS FORMATION;684
7.2.4;EFFECT OF ROS AND NO ON CORONARY RISK FACTORS: DIABETES;684
7.2.5;EFFECT OF ROS AND NO ON CORONARY RISK FACTORS: SMOKING;686
7.2.6;EFFECT OF ROS AND NO ON CORONARY RISK FACTORS: MENOPAUSE AND SEX STEROIDS;686
7.2.7;THE CROSS-TALK OF NO AND FREE RADICAL, ESPECIALLY NADPH OXIDASE-DERIVED SUPEROXIDE;690
7.2.8;EFFECT OF ROS AND NO ON CORONARY RISK FACTORS: AGING;692
7.2.9;CROSS RELATION BETWEEN CORONARY RISK FACTORS AND NO;696
7.2.10;CONCLUDING REMARKS;700
7.2.11;ACKNOWLEDGMENT;700
7.2.12;REFERENCES;700
7.3;Chapter 22 The Role of Oxidative Stress in Endothelial Dysfunction and Vascular Inflammation;712
7.3.1;ABSTRACT;712
7.3.2;INTRODUCTION;712
7.3.3;THE EMERGING GLOBAL EPIDEMIC: ATHEROSCLEROSIS, DIABETES MELLITUS AND AGING;713
7.3.4;THE REVOLUTIONARY CONCEPTS OF VASCULAR BIOLOGY;714
7.3.5;THE ENDOTHELIUM AND VASCULAR HOMEOSTASIS;715
7.3.6;ENDOTHELIAL DYSFUNCTION, ATHEROSCLEROSIS AND VASCULAR INFLAMMATION;716
7.3.7;PATHOPHYSIOLOGICAL INSIGHTS;718
7.3.8;VASCULAR SOURCES OF OXIDATIVE STRESS;721
7.3.9;FINAL COMMON MOLECULAR PATHWAYS OF ATHEROSCLEROSIS, DIABETES AND AGING;729
7.3.10;ROS AND ATHEROSCLEROSIS;731
7.3.11;DIABETES;735
7.3.12;AGING;739
7.3.13;CONCLUSION;742
7.3.14;REFERENCES;742
7.4;Chapter 23 Nitric Oxide, Oxidative Stress, Immune Response and Critical Care;762
7.4.1;SUMMARY;762
7.4.2;INTRODUCTION;762
7.4.3;NO AND ENDOTHELIAL DYSFUNCTION;763
7.4.4;NO AND ISCHEMIA/REPERFUSION INJURY;764
7.4.5;NO AND SEPSIS;766
7.4.6;NO AND ALI/ARDS;768
7.4.7;REFERENCES;769
7.5;Chapter 24 Reactive Metabolites of Oxygen and Nitrogen in Liver Ischemia and Reperfusion Injury;780
7.5.1;ABSTRACT;780
7.5.2;INTRODUCTION;780
7.5.3;I/R INCREASES ROS PRODUCTION, DECREASES NO BIOAVAILABILITY AND ALTERS THE REDOX STATE OF THE LIVER: A RECIPE FOR DISASTER;782
7.5.4;MECHANISMS OF SUPEROXIDE-DEPENDENT TISSUE INJURY;785
7.5.5;ROLE OF LEUKOCYTES IN I/R INJURY;791
7.5.6;REGULATION OF I/R-INDUCED LIVER DAMAGE BY ENDOGENOUS NO;792
7.5.7;PROTECTION OF POST-ISCHEMIC LIVER BY eNOS-INDEPENDENT GENERATION OF NO;793
7.5.8;CONCLUDING REMARKS;795
7.5.9;REFERENCES;796
7.6;Chapter 25 Nitric Oxide in Airway Inflammation;802
7.6.1;ABSTRACT;802
7.6.2;INTRODUCTION;802
7.6.3;LOCALIZATION OF NO IN AIRWAYS;803
7.6.4;NO IN PATHOPHYSIOLOGY OF LUNG;803
7.6.5;NO AND SIGNAL TRANSDUCTION IN AIRWAYS;806
7.6.6;PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS (PPARS);807
7.6.7;NO AND OXIDATIVE STRESS IN AIRWAY;808
7.6.8;CONCLUSION AND FUTURE PERSPECTIVES;808
7.6.9;ACKNOWLEDGMENTS;809
7.6.10;REFERENCES;809
7.7;Chapter 26 Novel Therapeutic Applications of Nitric Oxide in the Inhibition of Tumor Malignancy and Reversal of Resistance;820
7.7.1;SUMMARY;820
7.7.2;INTRODUCTION;820
7.7.3;CHEMISTRY, CELLULAR SOURCE, BIOCHEMICAL ACTIVITIES MEDIATED BY NO, AND ROLE IN HEALTH AND DISEASE;822
7.7.4;THERAPEUTIC AND PREVENTIVE EFFECTS OF NO IN CANCER;823
7.7.5;CHEMOPREVENTIVE ROLE OF NO IN CANCER;824
7.7.6;DIRECT ANTI-TUMOR ROLE OF NO IN CANCER;824
7.7.7;SENSITIZING ACTIVITIES OF NO TO APOPTOSIS BY THERAPEUTICS;825
7.7.8;NO INHIBITS EMT AND METASTASIS;828
7.7.9;PRECLINICAL THERAPEUTIC EFFICACY OF NO IN CANCER;828
7.7.10;THERAPEUTIC EFFICACY OF NO IN CANCER PATIENTS;828
7.7.11;CONCLUDING REMARKS;829
7.7.12;ACKNOWLEDGMENTS;830
7.7.13;REFERENCES;830
8;Index;838
8.1;A;838
8.2;B;839
8.3;C;839
8.4;D;840
8.5;E;841
8.6;F;841
8.7;G;842
8.8;H;842
8.9;I;843
8.10;J;844
8.11;K;844
8.12;L;844
8.13;M;844
8.14;N;845
8.15;O;847
8.16;P;847
8.17;Q;849
8.18;R;849
8.19;S;849
8.20;T;850
8.21;U;851
8.22;V;851
8.23;W;851
8.24;X;851
8.25;Y;852
8.26;Z;852