ECTO-NOX proteins: growth, cancer, and aging
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| Format: | Buch |
| Sprache: | English |
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New York, NY [u.a.]
Springer
2013
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| Schriftenreihe: | Life sciences
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| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XVI, 507 S. Ill., graph. Darst. |
| ISBN: | 9781461439578 |
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Datensatz im Suchindex
| _version_ | 1804149360904110080 |
|---|---|
| adam_text | Titel: ECTO-NOX proteins
Autor: Morré, Durward James
Jahr: 2013
Contents
The ENOX Protein Family..................................................................... 1
1.1 The ENOX Protein Family Members............................................ 1
1.2 ENOX Proteins Are Associated with the External Cell
Surface as Ecto Proteins and Are Shed into the Environment....... 4
1.3 Two Activities of ENOX Proteins Alternate.................................. 6
1.4 ENOX Proteins Participate Directly in the Enlargement
Phase of Cell Growth..................................................................... 7
1.5 ENOX Proteins Are Resistant to Degradation and Tend
to Form Insoluble Aggregates........................................................ 7
1.6 ENOX Proteins Are Dicopper Proteins Lacking Both
Iron and Flavin............................................................................... 8
1.7 The Oscillatory Behavior Complicates Assays of ENOX
Activities........................................................................................ 10
1.8 The Distinctive 2+3 Pattern of ENOX Oscillations
Is a Unifying Characteristic of All Family Members..................... 11
1.9 ENOX Proteins Differ Markedly from the NOX Proteins
of Host Defense.............................................................................. 13
1.10 ENOX Proteins Are of Low Specific Activity............................... 14
1.10.1 Natural Electron Donors and Acceptors for Cell
Surface-Associated ENOX Proteins................................ 14
1.10.2 Hydroquinones as Natural Electron Donors.................... 15
1.10.3 Reduced Pyridine Nucleotides as Artificial
Electron Donors............................................................... 15
1.10.4 Protein Thiols and Tyrosines as Electron Donors
for arNOX Proteins and Generation of Superoxide......... 15
1.10.5 Aggregation and Formation of Amyloid.......................... 16
1.11 Why an External NADH Oxidase?................................................ 17
1.12 Summary........................................................................................ 17
L Contents
2 Measurements of ECTO-NOX (ENOX) Activities............................... 19
2.1 Spectrophotometric Assay of NADH Oxidase.............................. 21
2.2 Statistical Analysis......................................................................... 22
2.3 Data Reduction Methods................................................................ 23
2.3.1 Diode Array Instruments.................................................... 30
2.4 Measurement of Hydroquinone Oxidase Activity
with Reduced Coenzyme Q10 or Phylloquinone as Substrate........ 32
2.4.1 Enzyme Assay for Reduced Coenzyme Q10 Oxidase......... 32
2.4.2 Enzyme Assay for Reduced Phylloquinone Oxidase......... 33
2.5 Dissolved Oxygen Measurement................................................... 35
2.6 Estimation of Protein Disulfide-Thiol Interchange Activity.......... 38
2.7 Preparation of Scrambled RNase Substrate................................... 38
2.8 Estimates of Protein Disulfide-Thiol Interchange from
Enzymatic Assay of Dipyridyl-Difhio Substrate Cleavage............ 41
2.9 Measurement of Trans-Plasma Membrane Redox
by Reduction of Cell-Impermeable Dyes...................................... 42
2.9.1 CoQj Can Function as an Intermediate Electron
Carrier in WST-1 Reduction............................................... 42
2.9.2 Measurement of Plasma Membrane Electron
Transport Based on WST-1 Reduction............................... 42
2.10 Summary........................................................................................ 44
3 The Constitutive ENOX1 (CNOX)........................................................ 47
3.1 ENOX1 Function........................................................................... 47
3.2 ENOX1 Cloning............................................................................. 50
3.3 ENOX1 Characterization............................................................... 53
3.4 ENOX1 Activity Requires the Presence of Copper....................... 57
3.5 Copper Binding and Site-Directed Mutagenesis
of Potential Copper-Binding Sites................................................. 58
3.6 Response to Nucleotides................................................................ 60
3.7 Aggregation and Electron Microscopy.......................................... 61
3.8 ENOX1 Fulfills Essential Roles in Cell Enlargement
and Cellular Time-Keeping............................................................ 62
3.9 ENOX1 of Human Platelets........................................................... 62
3.10 Summary........................................................................................ 62
4 Role in Plasma Membrane Electron Transport................................... 65
4.1 Composition of the PMET............................................................. 65
4.1.1 NADH Coenzyme Q Reductases....................................... 66
4.1.2 Hydroquinones................................................................... 68
4.1.3 Terminal Oxidases.............................................................. 69
4.2 Electron Donors and Acceptors..................................................... 73
4.3 Rates of PMET............................................................................... 73
4.4 Energetics of PMET....................................................................... 76
4.5 PMET Driven Outward Proton Pumping
and Alkalinization of the Cytoplasm.............................................. 78
Contents
4.6 PMET Function in Electron Import............................................... 80
4.7 PMET and Growth......................................................................... 81
4.7.1 Cell Cycle Check Point Control of Cell
Enlargement...................................................................... 81
4.7.2 PMET Activity and Growth Are Correlated..................... 82
4.8 Regulation of PMET...................................................................... 82
4.8.1 Feedback Regulation of PMET........................................ 85
4.8.2 ENOX Cell Surface Receptor Proteins............................ 86
4.9 PMET and Glycolysis.................................................................... 86
4.9.1 PMET and Glycolysis of Cancer Cells............................. 86
4.10 PMET Links to Major Signaling Pathways................................... 88
4.10.1 Sirtuins............................................................................. 89
4.10.2 Sphingolipid Rheostat...................................................... 91
4.10.3 NADH Modulation of PTEN Provides Link
of PMET to Ras-Raf-Mek-Erk, PI3-AKT-mTOR
and NF-icB....................................................................... 91
4.10.4 AMP-Activated Protein Kinase........................................ 93
4.10.5 Hypoxia............................................................................ 93
4.11 NAD+Homeostasis........................................................................ 95
4.12 Summary........................................................................................ 95
Role in the Enlargement Phase of Cell Growth................................... 97
5.1 Cell Enlargement Linked to ENOX Activities............................... 97
5.2 ECTO NADH Oxidase of Liver Plasma Membranes
Stimulated by Hormones and Growth Factors............................... 98
5.3 ECTO NADH Oxidase of Rat Hepatoma Plasma
Membrane Constitutively Activated and No Longer
Growth Factor or Hormone-Responsive........................................ 98
5.3.1 Thiol Reagents.................................................................. 100
5.4 Relationship to Growth.................................................................. 101
5.4.1 Plants................................................................................ 101
5.4.2 Vertebrate Cells................................................................ 113
5.5 Pathological Implications............................................................... 123
5.5.1 Apoptosis.......................................................................... 123
5.6 Physical Membrane Displacements............................................... 124
5.7 ATP- and p97 AAA-ATPase-Dependent and Drug-Inhibited
Vesicle Enlargement Reconstituted Using Synthetic Lipids
and Recombinant Proteins............................................................. 124
5.8 Summary........................................................................................ 138
Roles as Ultradian Oscillators of the Cells Biological Clock............... 141
6.1 Time Keeping Properties............................................................... 141
6.2 Molecular Studies.......................................................................... 142
6.3 Studies with Deuterium Oxide....................................................... 148
6.4 The Role of Copper........................................................................ 149
6.5 The Copper Clock.......................................................................... 150
Contents
6.6 EXAFS Investigations................................................................... 152
6.7 Oscillations Inherent in the Structure of Water.............................. 154
6.8 Period Length Determined by Ionic Radius
of Liganded Cation........................................................................ 158
6.9 Spectral Evidence for Disequilibrium of ortho.para
Spin States in Liquid Water That Oscillate.................................... 161
6.10 Other Mechanisms Proposed for ortho/para Conversions
and Departures from Their Equilibrium Ratio of 3:1.................... 164
6.11 The 24-min Period Has Properties of a Carrier Wave
Generated from the Basic Underlying ortho-para
Water Oscillations? The Heart Rate Model................................... 166
6.11.1 Growth Oscillations of Elongating Pollen Tubes............. 168
6.12 Phasing of the Rhythm................................................................... 168
6.12.1 EMF Sets the Copper Clock............................................. 169
6.13 A Mechanism to Explain How Oscillations of Redox
Potential of Aqueous Solutions Become Synchronous
and Remain So............................................................................... 172
6.14 ENOX Clock and Cancer............................................................... 177
6.15 Are ENOX Oscillators Linked to the Drivers
of the Orcadian Clock and How Are They Linked?...................... 178
6.16 Why Oscillate ? A Consequence of Active Sites
in Metalloproteins?........................................................................ 184
6.17 Summary........................................................................................ 185
Other Potential Functional Roles of ENOX Proteins.......................... 187
7.1 Cell Cycle Control......................................................................... 187
7.2 Gene Regulation............................................................................. 187
7.3 Endomembrane Function, Membrane Displacements,
Vesicle Budding............................................................................. 188
7.3.1 Membrane Budding.......................................................... 188
7.3.2 Energy Requirements for Physical Membrane
Displacement.................................................................... 190
7.4 Endocytosis and Autophagy........................................................... 192
7.5 Host Defense.................................................................................. 193
7.6 pH Control..................................................................................... 193
7.7 Lipid Oxidation.............................................................................. 195
7.7.1 arNOX Inhibitors and Prevention of Coronary
Artery Disease.................................................................. 197
7.8 Life Extension and Calorie Restriction.......................................... 197
7.9 Control of Apoptosis and Cell Survival......................................... 198
7.10 Neurodegenerative Disorders......................................................... 200
7.11 Memory.......................................................................................... 201
7.12 Gametogenesis............................................................................... 202
Contents
7.13 Role in Viral Pathogenesis............................................................. 203
7.13.1 ENOX2 Inhibitor (-)-Epigallocatechin-3-Gallate
Blocks Virus Infections Alone and in Combination
with Capsicum Vanilloids and Other Green
Tea Catechins................................................................... 205
7.13.2 Brefeldin A and Antitumor Quassinoids........................... 207
7.14 Summary........................................................................................ 209
ENOX2 (tNOX) and Cancer.................................................................. 211
8.1 ENOX2 Discovery......................................................................... 211
8.2 ENOX2 Activity............................................................................. 213
8.2.1 Biochemistry.................................................................... 217
8.3 Sequence........................................................................................ 218
8.4 Structural Properties....................................................................... 222
8.4.1 ENOX2 Protein Phosphorylation..................................... 228
8.5 ENOX2 Presence and Cancer........................................................ 228
8.5.1 ENOX2 Autoantibodies Generated
in Cancer Patients............................................................. 230
8.5.2 ENOX2 Gene Present in Genome as a Single Copy........ 230
8.5.3 ENOX2 Lacks Intrinsic Membrane-Binding Motifs........ 230
8.5.4 ENOX2 Has Properties of a Prion and
Is Protease Resistant......................................................... 231
8.6 ENOX2 Has Characteristics of an Oncofetal Protein.................... 233
8.7 Transgenic Mouse Strain Overexpressing ENOX2....................... 235
8.8 Alternative Splicing as Basis for Specific ENOX2
Localization to the Cell Surface..................................................... 242
8.8.1 Full-Length ENOX2 MRNA Identical to That
of Cancer Cells Exists in Human Non-cancer Cells
and Tissues....................................................................... 247
8.8.2 Full-Length 71 kDa ENOX2 Protein
Not Translated.................................................................. 248
8.8.3 Cancer-Specific Expression of ENOX2........................... 250
8.8.4 Splice Variants of ENOX2 Were Found
in Cancer Cells................................................................. 250
8.8.5 Expression of Exon 4 Minus and Exon 5 Minus
Forms of ENOX2 in COS Cells....................................... 250
8.8.6 Delivery of 34 kDa ENOX2 Protein to the
Plasma Membrane............................................................ 252
8.8.7 Mutation of Met 231 Blocked Expression
of the Exon 4 Minus Splice Variant.................................. 252
8.8.8 Subcellular Localization of E4m ENOX2-EGFP
and Full-Length ENOX2-EGFP Fusion Proteins............. 253
8.8.9 Regulation of ENOX2 Expression................................... 256
8.9 hnRNP F Splicing Factor Directs Formation
of the Exon 4 Minus Variant of ENOX2........................................ 257
8.10 Summary........................................................................................ 259
xiv Contents
9 Age-Related ENOX Proteins (arNOX).................................................. 261
9.1 arNOX Discovery.......................................................................... 264
9.2 Measurement of Superoxide Formation by arNOX....................... 266
9.3 Characteristics................................................................................ 268
9.4 arNOX Cloning.............................................................................. 272
9.5 Characterization of Recombinant arNOX Proteins........................ 279
9.6 arNOX as a Biomarker of Aging................................................... 284
9.7 Role in Skin Aging......................................................................... 286
9.8 Role in Oxidation of Serum Lipoproteins...................................... 291
9.9 arNOX Activity Correlates with Life Span in Sea Urchins........... 297
9.10 arNOX in Plants............................................................................. 298
9.11 arNOX Inhibitors........................................................................... 299
9.11.1 Coenzyme Q..................................................................... 299
9.11.2 Botanical Sources of arNOX Inhibitors........................... 305
9.12 Beneficial Biological Function Associated with Superoxide
Production: Physiological Roles of Superoxide............................ 307
9.13 NQOl (Cytoplasmic NAD(P)H: Quinone Oxidoreductases,
DT-Diaphorase EC 1.6.99.2) and Plasma Membrane
Electron Transport.......................................................................... 309
9.14 Summary........................................................................................ 310
10 The Auxin-Stimulated ENOX and Auxin Stimulation
of Plant Growth....................................................................................... 313
10.1 Early Evidence for Auxin-Modulated Enzymes Involved
in Plant Cell Enlargement.............................................................. 313
10.2 The Plasma Membrane as the Subcellular Location
of the Auxin-Responsive Mechanism............................................ 317
10.3 Direct Effects of Auxin on Signaling Molecules Fail
to Parallel Those of Mammalian Growth Factors.......................... 318
10.4 Evidence for a Redox-Related Plasma
Membrane-Located Auxin Target.................................................. 321
10.4.1 Separation of Auxin-Activated and Constitutive
NADH Oxidase Activities................................................ 327
10.5 Auxin-Stimulated NADH Activity and Growth
Oscillates with a Period Length of 24 min..................................... 327
10.6 Golgi Apparatus Transport Important to Sustained
Cell Enlargement but not Specifically Required
for Auxin-Induced Cell Enlargement............................................. 331
10.7 Response of ENOX of Isolated Plasma Membrane
Vesicles to Osmotica...................................................................... 331
10.8 Inhibitors of the Auxin-Stimulated NADH Oxidase
of Plants......................................................................................... 332
10.9 Cell Elongation Oscillates with a Period of 24 min
and Exhibits a Second set of Oscillations in Response
to2,4-D.......................................................................................... 335
Contents xv
10.10 The Auxin-Stimulated ENOX Has Properties of a Prion:
How 2,4-D Kills Plants................................................................ 337
10.11 Summary...................................................................................... 347
11 Cancer Therapeutic Applications of ENOX2 Proteins........................ 345
11.1 PMET as a Target for Anticancer Drug Development................. 348
11.1.1 Arsenicals as Unspecific Anticancer PMET
Inhibitors....................................................................... 349
11.2 Inhibition of PMET and Induction of Apoptosis......................... 350
11.2.1 Mechanism of Induction of Apoptosis When
Plasma Membrane Electron Transport
Is Inhibited.................................................................... 351
11.3 Mechanism of Growth Arrest When Plasma Membrane
Electron Transport Is Inhibited.................................................... 355
11.3.1 Elevation of Ceramide.................................................. 355
11.3.2 Links for Elevated Ceramide and Cell
Cycle Arrest.................................................................. 355
11.3.3 ENOX2 Inhibitors Slow the Growth of HeLa
Cells and Induce Apoptosis in Cancer But Not
in Noncancer Cells....................................................... 356
11.3.4 ENOX Inhibitors Increase Cytosolic
NADH Levels............................................................... 358
11.3.5 Increased NADH Resulting from ENOX2 Cell
Surface Inhibition Inhibits Plasma Membrane-
Associated Sphingosine Kinase (SK) and Lowers
Levels of Prosurvival Sphingosine-1-Phosphate.......... 359
11.3.6 Sphingomyelinase......................................................... 359
11.4 ENOX2 Inhibitors........................................................................ 362
11.4.1 Vanilloids (Capsaicinoids) as PMET Inhibitors........... 363
11.4.2 Anthracycline Antibiotics............................................. 368
11.4.3 Cisplatin Targets ENOX2 of the PMET....................... 377
11.4.4 Antitumor Sulfonylureas.............................................. 378
11.4.5 Antitumor Quassinoids Target ENOX2........................ 387
11.4.6 Acetogenins.................................................................. 390
11.4.7 EGCg............................................................................ 391
11.4.8 Phenoxodiol Targets the PMET Through
Inhibition of ENOX2.................................................... 400
11.4.9 Sulforaphane................................................................. 408
11.4.10 Suramin......................................................................... 409
11.4.11 Callipeltin..................................................................... 409
11.5 Nonsteroidal Anti-inflammatory Drugs....................................... 410
11.6 Retinoids and Calcitriol Agents of Differentiation...................... 411
11.6.1 Retinoic Acid Inhibition of PMET............................... 411
11.6.2 Retinoid Inhibition of ENOX2..................................... 411
11.7 ENOX2-Directed Therapeutic Antibodies................................... 412
xvi Contents
11.8 Antisense...................................................................................... 414
11.9 ENOX Inhibitors Enhance the Response
of Tumors to Radiation................................................................ 415
11.10 ENOX2 as a Target for Cancer Prevention Through
Early Intervention........................................................................ 415
11.11 Summary...................................................................................... 416
12 Cancer Diagnostic Applications of ENOX2 Proteins........................... 419
12.1 Cancer Cell Surface ENOX2 Shed into Sera as Biomarkers
of Cancer Presence....................................................................... 420
12.1.1 Biomarker Discovery Based on ENOX2 Activity.......... 421
12.1.2 Characteristics of ENOX2 as Cancer Biomarker
Based on Activity........................................................... 421
12.1.3 Transcript Variants Detected by Two-
Dimensional Gel-Western Blot Analysis
Are Cancer Site-Specific Biomarkers............................. 424
12.1.4 Transcript Variants of ENOX2....................................... 425
12.2 Two-Dimensional Gel-Western Blot Cancer
Detection System......................................................................... 425
12.2.1 Two-Dimensional Gel-Western Blot Analysis
of ENOX2 Transcript Variants Provide
for Very Early Detection................................................. 428
12.3 Early Intervention........................................................................ 430
12.4 ENOX2 Autoantibodies May Preclude Conventional
ELISA Tests for Early Appearance of ENOX2
in Serum or Plasma...................................................................... 430
12.5 Lipid-Associated Sialic Acid (LASA) Fractions
from Sera of Cancer Patients Contain ENOX2 Fragments
as Major Nonlipid Constituents................................................... 432
12.6 RTPCR Detection of Cancer Cells in Blood Based
on Presence of ENOX2 Splice Variant mRNA............................ 433
12.7 Summary...................................................................................... 433
Epilogue—Remaining Challenges................................................................. 435
Appendix Detailed Description of Two Dimensional Gel
Electrophoresis-Western Blot Early Cancer
Detection Protocol...................................................................... 441
References........................................................................................................ 443
Index................................................................................................................. 493
|
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| author | Morré, Durward James 1935- Morré, Dorothy M. |
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| author_sort | Morré, Durward James 1935- |
| author_variant | d j m dj djm d m m dm dmm |
| building | Verbundindex |
| bvnumber | BV040329631 |
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| ctrlnum | (OCoLC)802741633 (DE-599)BVBBV040329631 |
| discipline | Biologie |
| format | Book |
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| id | DE-604.BV040329631 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T00:21:48Z |
| institution | BVB |
| isbn | 9781461439578 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-025184080 |
| oclc_num | 802741633 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR |
| owner_facet | DE-355 DE-BY-UBR |
| physical | XVI, 507 S. Ill., graph. Darst. |
| publishDate | 2013 |
| publishDateSearch | 2013 |
| publishDateSort | 2013 |
| publisher | Springer |
| record_format | marc |
| series2 | Life sciences |
| spelling | Morré, Durward James 1935- Verfasser (DE-588)137838271 aut ECTO-NOX proteins growth, cancer, and aging D. James Morré ; Dorothy M. Morré New York, NY [u.a.] Springer 2013 XVI, 507 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Life sciences Proteine (DE-588)4076388-2 gnd rswk-swf Altern (DE-588)4068596-2 gnd rswk-swf Tumor (DE-588)4078460-5 gnd rswk-swf Zellwachstum (DE-588)4190674-3 gnd rswk-swf Zellwachstum (DE-588)4190674-3 s Tumor (DE-588)4078460-5 s Proteine (DE-588)4076388-2 s DE-604 Altern (DE-588)4068596-2 s b DE-604 Morré, Dorothy M. Verfasser aut HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025184080&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Morré, Durward James 1935- Morré, Dorothy M. ECTO-NOX proteins growth, cancer, and aging Proteine (DE-588)4076388-2 gnd Altern (DE-588)4068596-2 gnd Tumor (DE-588)4078460-5 gnd Zellwachstum (DE-588)4190674-3 gnd |
| subject_GND | (DE-588)4076388-2 (DE-588)4068596-2 (DE-588)4078460-5 (DE-588)4190674-3 |
| title | ECTO-NOX proteins growth, cancer, and aging |
| title_auth | ECTO-NOX proteins growth, cancer, and aging |
| title_exact_search | ECTO-NOX proteins growth, cancer, and aging |
| title_full | ECTO-NOX proteins growth, cancer, and aging D. James Morré ; Dorothy M. Morré |
| title_fullStr | ECTO-NOX proteins growth, cancer, and aging D. James Morré ; Dorothy M. Morré |
| title_full_unstemmed | ECTO-NOX proteins growth, cancer, and aging D. James Morré ; Dorothy M. Morré |
| title_short | ECTO-NOX proteins |
| title_sort | ecto nox proteins growth cancer and aging |
| title_sub | growth, cancer, and aging |
| topic | Proteine (DE-588)4076388-2 gnd Altern (DE-588)4068596-2 gnd Tumor (DE-588)4078460-5 gnd Zellwachstum (DE-588)4190674-3 gnd |
| topic_facet | Proteine Altern Tumor Zellwachstum |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=025184080&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT morredurwardjames ectonoxproteinsgrowthcancerandaging AT morredorothym ectonoxproteinsgrowthcancerandaging |