Cellular and Molecular Biology of Metals

Cellular and Molecular Biology of Metals......Page 2
Contents......Page 4
Preface......Page 6
Editors......Page 8
Contributors......Page 10
CONTENTS......Page 12
1.2 INTRODUCTION TO INORGANIC BIOCHEMISTRY RELATEDTO METAL ION TRAFFICKING......Page 13
1.2.1 METAL-LIGAND BINDING......Page 14
1.2.2 LIGAND SUBSTITUTION......Page 15
1.2.3 METAL ION EXCHANGE......Page 16
1.2.5 REDOX REACTION......Page 17
1.3.1 CELLULAR Zn2+ TRAFFICKING IN RELATION TO APO-METALLOTHIONEIN......Page 18
1.3.3 IN VITRO REACTIONS OF APO-MT AND GSH WITH Zn-PROTEINS: A MODEL FORLIGAND SUBSTITUTION DEACTIVATION......Page 21
1.3.4 NUTRIENT Zn2 DEFICIENCY AND APO-MT: IMPLICATIONS FOR Zn2 TRAFFICKING......Page 22
1.3.5 UTILIZATION OF METAL BINDING LIGANDS TO INDUCE INTRACELLULARMETAL ION DEFICIENCY......Page 24
1.3.7 METALLOTHIONEIN AND INTRACELLULAR COMPETITION FOR TOXIC METAL IONS......Page 26
1.4.1 Zn-PROTEINS THAT UNDERGO METAL ION EXCHANGE WITH Cd2+: METALLOTHIONEIN......Page 27
1.4.2 Zn-PROTEINS THAT UNDERGO METAL ION EXCHANGE WITH Cd2 : Zn-FINGER PROTEINS......Page 29
1.5.1 FLUORESCENT Zn2+ SENSORS IN RELATION TO Zn2 TRAFFICKING......Page 31
1.5.3 WHAT IS TSQ IMAGING IN CELLS?......Page 32
1.6.1 IRON TRAFFICKING AND PHARMACEUTICAL LIGANDS FOR Fe OVERLOAD DISORDER......Page 33
1.6.2.2 Reactions with Nitric Oxide Species......Page 35
1.7 CONCLUSIONS......Page 36
REFERENCES......Page 37
CONTENTS......Page 46
2.1 INTRODUCTION......Page 47
2.2.1 RENAL DISPOSITION OF MERCURY......Page 49
2.2.2.2 Role of Low- Molecular- Weight Thiols in the Proximal Tubular Absorption of Mercury......Page 50
2.2.3.2 GSH S-Conjugates of Mercury in the Lumen of the Proximal Tubule......Page 51
2.2.3.3 Role of Cysteinylglycinase......Page 53
2.2.3.5 Mercuric Conjugates of Cys as a Primary Transportable Form of Mercury at the Luminal Plasma Membrane......Page 54
2.2.3.6 Mercuric Conjugates of Hcy as a Transportable Form of Mercury at the Luminal Plasma Membrane......Page 55
2.2.3.7 Molecular \" Mimicry\" and Homology......Page 57
2.2.4.1 Role of Organic Anion Transport Systems......Page 58
2.2.4.2 Role of the Dicarboxylate Transporter......Page 59
2.2.4.4 Mercuric Conjugates of Cys as Transportable Forms of Mercury at the Basolateral Membrane......Page 60
2.2.4.6 Membrane Transporters Implicated in the Basolateral Uptake of Thiol S-Conjugates of Mercury in Proximal Tubular Cells......Page 61
2.2.5 ROLE OF MRP PROTEINS IN THE LUMINAL EXPORT OF MERCURIC IONS......Page 62
2.2.6 ROLE OF THE LIVER IN THE RENAL TUBULAR UPTAKE OF MERCURY......Page 63
2.3 URINARY EXCRETION OF MERCURY......Page 64
2.4.1 MERCURY AND INTRACELLULAR MT METABOLISM......Page 66
2.4.2 MERCURY AND INTRACELLULAR GSH METABOLISM......Page 67
2.4.3 LIPID PEROXIDATION, OXIDATIVE STRESS, AND MERCURY......Page 68
2.4.4 RENAL MITOCHONDRIAL FUNCTION AND MERCURY......Page 69
2.4.6 ALTERATIONS IN (NA + K )-STIMULATED ATPASE INDUCED BY MERCURY......Page 70
2.4.8 BETWEEN MERCURIC IONS AND WATER CHANNELS......Page 71
2.4.10 INTERACTIONS BETWEEN MERCURY AND THE CYTOSKELETON......Page 72
2.6.1 INTRACELLULAR THIOLS AND THE RENAL ACCUMULATION AND TOXICITY OF MERCURY......Page 73
2.6.2 EXTRACELLULAR THIOLS AND THE RENAL ACCUMULATION AND TOXICITY OF MERCURY......Page 75
2.6.3 REDUCTIONS IN FUNCTIONING NEPHRONS AND COMPENSATORY TUBULAR HYPERTROPHY AND THE RENAL DISPOSITION AND TOXICITY OF MERCURY......Page 78
REFERENCES......Page 79
CONTENTS......Page 90
3.1 INTRODUCTION......Page 91
3.2 MODELS USED TO STUDY HEPATIC TRANSPORT......Page 92
3.3.1 HEPATIC MICROANATOMY......Page 93
3.3.2 FUNCTIONAL POLARITY......Page 94
3.3.3 BILE SECRETION AND BILIARY-HEPATIC CYCLE......Page 95
3.3.4 PARACELLULAR PATHWAY FOR BILIARY EXCRETION......Page 96
3.4 SINUSOIDAL UPTAKE OF METALS FROM BLOOD PLASMA, ANDSECRETION BACK INTO THE BLOODSTREAM......Page 97
3.4.1 TRANSPORT DURING MEMBRANE RECYCLING: ROLES OF TRANSFERRINAND CERULOPLASMIN......Page 98
3.4.2.2 CTR1 and CTR2, the Copper Uptake Transporters......Page 100
3.4.2.4 ZIP/SLC39 and ZNT/SLC30 in Zinc Uptake and Effl ux, Respectively......Page 103
3.4.2.5 Ferroportin, Hephaestin, and Hepcidin in Hepatic Iron Export......Page 104
3.4.3 UPTAKE AND EFFLUX ON SINUSOIDAL MEMBRANE CHANNELS AND PUMPS......Page 105
3.4.4 PERMEATION AS LIPID-SOLUBLE FORMS OR BY CONVECTION......Page 106
3.5.2 METAL UPTAKE AND RELEASE FROM ENDOSOMAL/LYSOSOMAL COMPARTMENTS:ATP7A, ATP7B, DMT1, AND ZNT2......Page 107
3.5.4 MITOCHONDRIAL METAL UPTAKE......Page 109
3.6.2.1 MRP2-Mediated Excretion of GSH Complexes and Other Complexes......Page 110
3.6.2.1.2 Reabsorption of Metals from Bile......Page 112
ACKNOWLEDGMENTS......Page 113
REFERENCES......Page 114
CONTENTS......Page 124
4.4 INTRACELLULAR BINDING......Page 125
4.7 KIDNEYS......Page 126
4.8 CARDIOVASCULAR SYSTEM......Page 127
4.10.2 CELLULAR IMMUNE EFFECTS......Page 128
4.10.3.4.1 Ferrochelatase......Page 129
4.13 MITIGATING FACTORS......Page 130
4.14.2.4 Mixtures Exposures......Page 131
4.15 NANOMATERIALS......Page 132
REFERENCES......Page 133
5.2 Mn: ESSENTIALITY AND TOXICITY......Page 138
5.3 Mn TRANSPORT IN THE LUNGS......Page 140
5.4.1 TF/TF RECEPTOR IN Mn TRANSPORT......Page 141
5.4.3 OLFACTORY BULB......Page 142
5.4.6 DOPAMINE TRANSPORTER (DAT): PUTATIVE Mn TRANSPORTER?......Page 144
5.5.1 NEUROCHEMICAL ALTERATIONS ASSOCIATED WITH Mn TOXICITY......Page 145
5.5.2 MITOCHONDRIA AND OXIDATIVE STRESS IN PD AND Mn-INDUCEDDAERGIC NEURODEGENERATION......Page 146
ACKNOWLEDGMENTS......Page 147
REFERENCES......Page 148
6.1 INTRODUCTION......Page 154
6.2 MT PROTEINS......Page 155
6.3 MT GENE STRUCTURE AND FUNCTION......Page 156
6.3.1.2 Induced MT Gene Transcription......Page 157
6.3.1.3 Metal Response Element-Binding Transcription Factor-1 (MTF-1)......Page 158
6.3.1.6 Cytokine and Stress-Mediated Induction......Page 160
6.3.1.8 Post-Transcriptional Regulation......Page 161
6.4.1 MTS AS ZINC BUFFERS......Page 162
6.5.2 MT AND CANCER......Page 164
6.5.3.1 MT, Diabetes, and Cardiac Toxicity......Page 166
6.5.4 MT AND NEUROLOGICAL FUNCTION......Page 167
ACKNOWLEDGMENT......Page 168
REFERENCES......Page 169
7.1 INTRODUCTION......Page 178
7.2.1.1 Inorganic Iron......Page 179
7.2.2.1 Transferrin......Page 180
7.2.2.3 Endosomal Ferrireductase......Page 181
7.2.3 THE IRON STORAGE PROTEIN, FERRITIN......Page 182
7.3.2 HEME TRANSPORT FROM THE MITOCHONDRION......Page 183
7.4 IRON HOMEOSTASIS......Page 184
7.4.1 REGULATION OF CELLULAR IRON METABOLISM: THE IRPS......Page 185
7.4.2 REGULATION OF SYSTEMIC IRON METABOLISM: THE IRON REGULATORYHORMONE, HEPCIDIN......Page 186
REFERENCES......Page 187
CONTENTS......Page 192
8.2 ZINC PROTEINS AND THE ZINC PROTEOME......Page 193
8.3 ZINC HOMEOSTATIC PROTEINS AND CELLULAR ZINC HOMEOSTASIS......Page 194
8.3.2 ZINC SENSORS......Page 196
8.3.3 METALLOTHIONEINS......Page 197
8.3.3.2 MT Traffi cking......Page 199
8.4.4 IDENTIFICATION OF THE MOLECULAR TARGETS OF THE ZINC SIGNAL......Page 200
8.4.5.3 Mitogen-Activated Protein Kinase......Page 202
8.4.6.2.1 Zinc and PTP Activity......Page 203
8.4.6.3 Zinc in the Assembly of Signaling Complexes......Page 204
8.5.1 SPECIALIZED CELLS THAT SECRETE ZINC......Page 205
8.5.1.1 Prostate......Page 206
8.5.1.2 Pancreas......Page 207
8.5.1.3 Neurons......Page 208
8.5.1.8 Intestine......Page 209
8.6.1 CELLS OF THE ADAPTIVE IMMUNE SYSTEM......Page 210
8.6.3 CYTOKINE PRODUCTION......Page 211
8.7 SYSTEMIC ZINC HOMEOSTASIS......Page 212
ACKNOWLEDGMENT......Page 213
REFERENCES......Page 214
9.1 INTRODUCTION......Page 224
9.2.1 GSH SYNTHESIS AND DEGRADATION......Page 225
9.2.2 PATHWAYS FOR INTERORGAN TRANSPORT OF GSH AND GSH S-CONJUGATES......Page 227
9.2.4 RENAL GSH AND GSH S-CONJUGATE TRANSPORT......Page 229
9.2.5 METALS AS GSH S-CONJUGATES: IMPLICATIONS FOR TISSUE DISTRIBUTION......Page 231
9.3.2 PLASMA THIOLS AND METAL DISPOSITION......Page 232
9.3.3.1.1 Exogenous GSH Infl uencing Intracellular GSH Levels......Page 233
9.3.3.1.2 Exogenous GSH as an Extracellular Ligand for Mercury and the Function ofMercury–GSH Complex as a Transport Form......Page 235
9.3.3.2 Uninephrectomy and Compensatory Renal Growth (NPX) Model......Page 236
9.3.4 CADMIUM TRANSPORT AND DISPOSITION......Page 237
9.3.5 ARSENIC METABOLISM AND DISPOSITION......Page 239
9.4.1 METAL-INDUCED CHANGES IN CELLULAR GSH STATUS......Page 240
9.4.2 REGULATION OF GENE EXPRESSION BY METALS......Page 243
REFERENCES......Page 244
CONTENTS......Page 252
10.1 INTRODUCTION......Page 253
10.2.2 INTESTINAL TRANSPORT OF AS......Page 254
10.2.3 RENAL TRANSPORT OF AS......Page 255
10.2.4 HEPATIC TRANSPORT OF AS......Page 256
10.3.1 ENDOCRINE DISRUPTION AND Cd2......Page 257
10.3.2 INTESTINAL TRANSPORT OF Cd2......Page 258
10.3.3 RENAL TRANSPORT OF Cd2......Page 260
10.3.4 HEPATIC TRANSPORT OF Cd2......Page 263
10.4 LEAD......Page 265
10.5 MERCURY......Page 268
10.5.1.1 Intestinal Transport of Hg2+......Page 269
10.5.1.2 Renal Transport of Hg2......Page 270
10.5.1.3 Hepatic Transport of Hg2+......Page 271
10.5.1.5 Intracellular Mimicry with Hg2......Page 272
10.5.2.2 Transport of CH3Hg in Erythrocytes......Page 273
10.5.2.3 Intestinal Transport of CH3Hg......Page 274
10.5.2.4 Renal Transport of CH3Hg......Page 275
10.5.2.6 Transport of CH3Hg in the Placenta......Page 276
10.6 SELENIUM......Page 277
10.7.2 CHROMATE......Page 279
10.7.4 VANADATE......Page 280
REFERENCES......Page 281
11.1 INTRODUCTION......Page 306
11.2 GASTROINTESTINAL SYSTEM......Page 307
11.2.1.1 Role of Metallothionein and Glutathione in Metal Detoxifi cation......Page 308
11.2.1.2 Role of Precipitation Granules in Metal Detoxifi cation......Page 309
11.2.1.3 Cation Transport Processes of Crustacean Digestive Tract and Renal Organs......Page 310
11.2.1.4.1 Epithelial Brush-Border Membrane......Page 311
11.2.1.4.2 Epithelial Basolateral Membrane......Page 313
11.2.1.4.3 Metal Transport and Sequestration by Epithelial Mitochondria......Page 314
11.2.1.4.4 Metal Transport and Sequestration by Epithelial ER......Page 315
11.2.1.4.5.1 Transport of Ionic Metals......Page 316
11.2.1.4.5.2 Transport of Heavy Metal–Thiol Conjugates......Page 318
11.2.2.1 Sodium and Chloride Transport and Intestinal Electrophysiology......Page 321
11.2.2.2 Heavy Metal Transport across Perfused Crustacean Intestine......Page 322
11.3 KIDNEYS......Page 325
11.3.1 TRANSPORT OF WATER, SODIUM, AND CHLORIDE, AND ROLE INOSMOREGULATION, BY THE KIDNEY......Page 326
11.3.3 CALCIUM REABSORPTION BY CRUSTACEAN ANTENNAL GLANDS......Page 327
11.3.4 SECRETION OF ORGANIC ANION AND CATION METABOLITES BY ANTENNAL GLANDS......Page 328
11.3.5 HEAVY METAL REGULATION BY THE RENAL OAT1......Page 330
REFERENCES......Page 331
12.1 INTRODUCTION......Page 338
12.2.1 INTEGRINS: CELL–MATRIX INTERACTIONS......Page 339
12.2.2.2 Cadherin Complex......Page 341
12.2.2.3 Gap Junctions......Page 342
12.3.1 INTEGRINS......Page 343
12.3.2 TIGHT JUNCTIONS AND CADHERIN/CATENIN COMPLEXES......Page 344
12.3.3 GAP JUNCTIONS......Page 345
12.4.1 GENE EXPRESSION......Page 346
12.4.3 PROTEIN PHOSPHORYLATION......Page 347
12.4.4 PROTEIN DEGRADATION......Page 348
12.5 CONCLUSIONS......Page 349
REFERENCES......Page 350
13.1 PHYSIOLOGY OF IRON HOMEOSTASIS......Page 362
13.2 HORMONAL REGULATION OF IRON TRAFFIC......Page 364
13.3.3 IRON OVERLOAD (HEMOCHROMATOSIS......Page 365
13.4 HEREDITARY HEMOCHROMATOSIS......Page 366
13.6 A UNIFYING CONCEPT FOR THE PATHOGENESIS OF HH......Page 367
13.8 OTHER RARE HEREDITARY CAUSES OF SYSTEMIC IRON OVERLOAD......Page 370
13.10 MITOCHONDRIAL IRON OVERLOAD......Page 371
13.11 TRANSFUSIONAL SIDEROSIS AND CHELATION THERAPY......Page 372
13.12 IRON OVERLOAD STATES SECONDARY TO CHRONIC LIVER DISEASES......Page 373
13.13 IRON OVERLOAD IN CHRONIC HEPATITIS C......Page 374
13.14 IRON OVERLOAD IN ALCOHOLIC LIVER DISEASE......Page 375
13.16 HEREDITARY HYPERFERRITINEMIA-CATARACT SYNDROME......Page 376
13.17 STEPWISE DECISIONAL TREE FOR THE CLINICAL MANAGEMENTOF IRON OVERLOAD STATES......Page 377
REFERENCES......Page 379
14.1 INTRODUCTION......Page 390
14.2.2 IRON AS AN IMMUNE REGULATOR......Page 391
14.2.3 THE ROLE OF ZINC IN IMMUNOLOGICAL FUNCTION......Page 392
14.3 IMMUNOTOXIC EFFECTS OF NONESSENTIAL METALS......Page 393
14.3.1 METALS, CELLULAR THIOLS, AND OXIDATIVE STRESS......Page 394
14.3.2 METAL INFLUENCES ON APOPTOTIC SIGNALING PATHWAYS......Page 397
14.3.4 INDUCTION OF MT BY METALS......Page 400
14.3.5 MT SYNTHESIS AND DISTRIBUTION......Page 401
14.3.7 REGULATION OF HSPS......Page 403
14.3.8 HSPS AND IMMUNE FUNCTION......Page 404
14.3.9 METAL-INDUCED HSPS IN IMMUNE CELLS......Page 405
14.3.10 METAL EXPOSURE CAN ALTER A VARIETY OF CELLULAR ACTIVITIES......Page 406
14.5.1 METAL-INDUCED HYPERSENSITIVITY......Page 407
14.5.2 HEAVY METALS AND AUTOIMMUNITY......Page 408
14.6 DETECTION AND ASSESSMENT OF METAL-MEDIATEDIMMUNOMODULATION......Page 409
REFERENCES......Page 411