Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English German |
| Veröffentlicht: |
2001
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. Sprache. - Würzburg, Univ., Diss., 2001 |
| Beschreibung: | 111 Bl. Ill., graph. Darst. |
Internformat
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| 245 | 1 | 0 | |a Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders |c von Amanda Wong |
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| 300 | |a 111 Bl. |b Ill., graph. Darst. | ||
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Datensatz im Suchindex
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| adam_text |
CONTENTS
SUMMARY (ENGLISH) 1
SUMMARY (GERMAN) 3
1. INTRODUCTION 6
1.1 ADVANCED GLYCATION ENDPRODUCTS (AGES): CHEMISTRY 6
1.2 GLYCATION PRECURSORS 7
1.3 STRUCTURAL IDENTIFICATION OF BIOLOGICALLY RELEVANT AGES 7
1.4 AGES IN AGING AND DEGENERATIVE DISEASES OF THE CARDIOVASCULAR SYSTEM
8
1.5 AGES IN AGING AND IN ALZHEIMER'S DISEASE (AD) 8
1.6 AD AND DIABETES 9
1.7 EVIDENCE FOR A CHRONIC SUB-ACUTE INFLAMMATORY PROCESS IN AD 9
1.8 INTERACTION OF AGES WITH CELLS OF THE CNS AND SUBSEQUENT OXIDATIVE
STRESS 10
1.9 AGES AND PARKINSON'S DISEASE 11
1.10 RECEPTORS FOR AGES AND AGE-INDUCED SIGNALING 12
1.11 COMBINATORIAL APPROACHES TO IMMUNOGENIC AGE-STRUCTURES.
(AGE-PEPTIDE 13
SPOT
LIBRARIES)
1.12 AIMS 14
2. MATERIAL AND METHODS 15
2.1 MATERIAL
15
2.1.1 CHEMICALS 15
2.1.2. PEPTIDE SYNTHESIS 15
2.1.3. ANTIBODIES 15
2.1.4 ANTIOXIDANTS ' 17
2.1.5 CELL CULTURE 17
2.1.6 CASES USED FOR IMMUNOHISTOCHEMISTRY 17
ALZHEIMER'S DISEASE (AD) 17
INCIDENTAL LEWY BODY DISEASE 19
2.2 METHODS
20
2.2.1. PRODUCTION OF AGES 20
2.2.1.1 BSA AND CHICKEN EGG ALBUMIN AGE 20
2.2.1.2. P-AMYLOID AGE 20
BIBLIOGRAFISCHE INFORMATIONEN
HTTP://D-NB.INFO/963112082
2.2.2. CML-CONTENT 21
2.2.3. ENDOTOXIN ASSAY 21
2.2.4. PROTEIN DETERMINATION 22
2.2.5. FLUORESCENCE MEASUREMENTS 22
2.2.5.1 AGES 22
2.2.5.2 DETECTION OF PA4 FIBRILS USING THIOFLAVIN T - FLUORESCENCE 22
2.2.6. CELL CULTURE ' 23
2.2.6.1 PRODUCTION OF CELL CULTURE MEDIUM 23
2.2.6.2 CELL LINE 23
2.2.6.3 CELL CULTURE TECHNIQUES 23
2.2.6.4 CELL COUNTS 24
2.2.6.5 FREEZING AND THAWING OF CELLS 24
2.2.7. MTT ASSAY ' ' ^ 25
2.2.8. INCUBATION WITH ANTIOXIDANTS 25
2.2.9. NO DETERMINATION 26
2.2.10. CELL LYSIS AND SDS-PAGE 26
2.2.11. WESTERN BLOT FOR DETECTION OF INDUCIBLE NO SYNTHASE 27
2.2.12. RNA ISOLATION 27
2.2.13. RT-PCR 28
2.2.14. DATA ANALYSIS 28
2.2.15. IMMUNOHISTOCHEMISTRY 29
2.2.15.1 PREPARATION OF TISSUE FOR CASES WITH AD 29
2.2.15.2 IMMUNOHISTOCHEMISTRY FOR CASES WITH AD 29
2.2.15.3 PREPARATION OF TISSUE FOR CASES WITH INCIDENTAL LEWY BODY
DISEASE 30
2.2.15.4. IMMUNOHISTOCHEMISTRY FOR CASES WITH INCIDENTAL LEWY BODY
DISEASE 31
2.2.16. SYNTHESIS OF THE DIPEPTIDE/TRIPEPTIDE LIBRARY. ' 32
2.2.16.1 GENERAL DESCRIPTION 32
2.2.16.2 PROTOCOL FOR SYNTHESIS OF THE PALA-PALA ANCHOR 33
2.2.16.3 PROTOCOL FOR SYNTHESIS OF THE DI/TRIPEPTIDE LIBRARY 35
2.2.16.4 GLYCATION/RIBOSYLATION OF THE DI/TRIPEPTIDE LIBRARY 37
2.2.16.5. EPITOPE MAPPING WITH ANTI-AGE ANTIBODIES 38
2.2.16.6 STABILITY OF
14C-LABELED SPOTS 39
2.2.17.
OTHER BUFFERS AND SOLUTIONS 39
2.3 EQUIPMENT
41
2.4. SOFTWARE 41
3. RESULTS 42
3.1. AGE-MODIFIED PROTEINS INDUCE THE EXPRESSION OF INOS, LEADING TO THE
42
PRODUCTION OF NO IN MICROGLIA
3.1.1 CHARACTERISTICS OF BSA AND AGE PREPARATIONS 42
3.1.2 AGE-MODIFIED MODEL PROTEINS INDUCE NO PRODUCTION IN MICROGLIA 43
3.1.3 A-OXOALDEHYDES DO NOT INDUCE NO PRODUCTION IN MICROGLIA 45
3.1.4 AGE-MODIFICATION INCREASES THE POTENCY OF PA4 FOR NO PRODUCTION 45
3.1.5 INDUCIBLE NITRIC OXIDE SYNTHASE (INOS) IS THE AGE-INDUCED NOS
ISOFORM 46
3.1.6 ANTIOXIDANTS INHIBIT AGE-INDUCED INOS EXPRESSION AND NO PRODUCTION
48
3.1.7 TOXICITY OF AGES AND A-OXALDEHYDES ON N-L 1 MICROGLIA 49
3.1.8
BSA.-AGE
INDUCE ACTIVATION OF
RAGE
' 51
3.2. IMMUNODETECTION OF AGE AND INOS IN THE BRAINS OF NORMAL AGED
INDIVIDUALS 53
AND CASES WITH ALZHEIMER'S AND INCIDENTAL LEWY BODY DISEASE.
3.2.1 COMPARISON OF AGE ANTIBODIES 53
3.2.2 DISTRIBUTION OF INOS AND AGE IN YOUNG AND OLD CONTROL TEMPORAL
CORTEX 55
3.2.3 DISTRIBUTION OF INOS AND AGE IN EARLY AD TEMPORAL CORTEX 55
3.2.4 DISTRIBUTION OF INOS AND AGE IN ADVANCED AD TEMPORAL CORTEX 55
3.2.5 COMPARISON BETWEEN THE DISTRIBUTION OF INOS AND AGE IN TEMPORAL
AND 56
ENTORHINAL CORTICES IN AD AND CONTROLS
3.2.6 DIFFERENTIAL PATTERN OF AGE/1NOS STAINING ACCORDING TO PLAQUE 57
DEVELOPMENT
3.2.7 DISTRIBUTION OF INOS AND AGE IN MICROGLIA IN ADVANCED AD TEMPORAL
58
CORTEX
3.2.8 AGE COLOCALISES WITH A-SYNUCLEIN IN THE SUBSTANTIA NIGRA IN
INCIDENTAL 59
LEWY
BODY DISEASE
3.3. CHARACTERIZATION OF ANTI-AGE ANTIBODIES WITH GLYCATED PEPTIDE
LIBRARIES ON 60
CELLULOSE
MEMBRANES (AGE-PEPTIDE SPOT LIBRARIES).
3.3.1 ASSEMBLY OF PEPTIDES ON MEMBRANES 60
3.3.1 GLYCATION REACTIVITIES OF AMINO ACID SIDE CHAINS 62
3.3.2 EPITOPE MAPPING USING
ANTI-AGE
ANTIBODIES 66
3.3.3 NON-SPECIFIC ANTIBODY REACTIVITY 71
3.3.4 STABILITY OF
14C-LABELED SPOTS 73
4. DISCUSSION 75
4.1 AGE-MEDIATED OXIDATIVE STRESS IN THE AGEING AND DISEASED BRAIN 75
4.2 AGES INDUCE NO PRODUCTION IN J774A.1 MACROPHAGES AND N-L 1
MICROGLIAL 75
CELLS
4.3 GLYCATION PRECURSORS AND OXIDATIVE STRESS 77
4.4 OXIDATIVE STRESS IN AD - A GLYCATION LINK? 78
4.4.1 AGE-AP, BUT NOT THE UNMODIFIED PEPTIDE, INDUCED NO PRODUCTION IN
N-L 1 78
MICROGLIA
4.4.2 AGE- PA4 PRODUCED A MORE POTENT EFFECT THAN UNMODIFIED, FIBRILLAR
PA4 79
4.4.3 AGES INDUCE INOS IN N-L 1 MICROGLIA 80
4.4.4 AGES ARE CO-LOCALISED WITH INOS IN THE AD BRAIN 81
4.4.5 ROLE OF GLIAL CELLS IN PRODUCING NO IN THE AD BRAIN 81
4.5 AGES IN PD ' ~~ 84
4.6 MEMBRANE PERMEABLE ANTIOXIDANTS AS ANTI-INFLAMMATORY AGENTS AND
INHIBIT 85
RADICAL AMPLIFICATION
4.6.1 ESTROGEN 85
4.6.2
GINGKO BILOBA EGB761 86
4.6.3 THIOCTIC (A-LIPOIC) ACID 86
4.6.4 N-TERT.-BUTYL-A-PHENYLNITRONE (PBN) 87
4.7 COMBINATORIAL APPROACHES TO IMMUNOGENIC AGE-STRUCTURCS.
CHARACTERIZATION 88
OF ANTI-AGE ANTIBODIES WITH GLYCATED PEPTIDE LIBRARIES ON CELLULOSE
MEMBRANES
(AGE-PEPTIDE SPOT LIBRARIES). '
4.7.1 W540 VERSUS APEG MEMBRANES 88
4.7.2 RELATIVE REACTIVITIES OF SUGARS WITH DIPEPTIDE LIBRARY 88
4.7.3 EPITOPE MAPPING WITH ANTI-AGE ANTIBODIES 90
J
4.8 CONCLUSIONS 91
REFERENCES 93
ABBREVIATIONS 110
APPENDIX
CURRICULUM VITAE (LEBENSLAUF)
LIST OF PUBLICATIONS
STATEMENT
ACKNOWLEDGEMENTS |
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| indexdate | 2024-10-09T18:06:33Z |
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| language | English German |
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| physical | 111 Bl. Ill., graph. Darst. |
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| spelling | Wong, Amanda 1973- Verfasser (DE-588)123348544 aut Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders von Amanda Wong 2001 111 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. Sprache. - Würzburg, Univ., Diss., 2001 Antioxidans (DE-588)4142729-4 gnd rswk-swf Maillard-Reaktion (DE-588)4168628-7 gnd rswk-swf Alzheimerkrankheit (DE-588)4112510-1 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Maillard-Reaktion (DE-588)4168628-7 s Alzheimerkrankheit (DE-588)4112510-1 s Antioxidans (DE-588)4142729-4 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=009458779&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Wong, Amanda 1973- Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders Antioxidans (DE-588)4142729-4 gnd Maillard-Reaktion (DE-588)4168628-7 gnd Alzheimerkrankheit (DE-588)4112510-1 gnd |
| subject_GND | (DE-588)4142729-4 (DE-588)4168628-7 (DE-588)4112510-1 (DE-588)4113937-9 |
| title | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders |
| title_auth | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders |
| title_exact_search | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders |
| title_full | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders von Amanda Wong |
| title_fullStr | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders von Amanda Wong |
| title_full_unstemmed | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders von Amanda Wong |
| title_short | Implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders |
| title_sort | implications of advanced glycation endproducts in oxidative stress and neurodegenerative disorders |
| topic | Antioxidans (DE-588)4142729-4 gnd Maillard-Reaktion (DE-588)4168628-7 gnd Alzheimerkrankheit (DE-588)4112510-1 gnd |
| topic_facet | Antioxidans Maillard-Reaktion Alzheimerkrankheit Hochschulschrift |
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