The role of the antioxidant protein sestrin 2 in emphysema development in mice:
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| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
Gießen
VVB Laufersweiler Verlag
2015
|
| Edition: | 1. Auflage |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis Inhaltstext Inhaltsverzeichnis |
| Physical Description: | XII, 148 Seiten Illustrationen, Diagramme |
| ISBN: | 9783835963184 |
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MARC
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| 100 | 1 | |a Fysikopoulos, Athanasios |e Verfasser |0 (DE-588)1079941282 |4 aut | |
| 245 | 1 | 0 | |a The role of the antioxidant protein sestrin 2 in emphysema development in mice |c submitted by Athanasios Fysikopoulos, Veterinarian from Athens, Greece |
| 250 | |a 1. Auflage | ||
| 264 | 1 | |a Gießen |b VVB Laufersweiler Verlag |c 2015 | |
| 300 | |a XII, 148 Seiten |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Justus-Liebig-Universität Gießen |d 2015 | ||
| 650 | 7 | |a protein |2 cabt | |
| 650 | 7 | |a mice |2 cabt | |
| 650 | 7 | |a Laporatory mammals |2 cabt | |
| 650 | 7 | |a antioxidant properties |2 cabt | |
| 650 | 7 | |a pulmonary emphysema |2 cabt | |
| 650 | 7 | |a respiratory diseases |2 cabt | |
| 650 | 7 | |a chronic obstructive pulmonary disease |2 cabt | |
| 653 | |a Aktuelle wissenschaftliche Publikation aus dem Bereich der Universitäten. | ||
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| 710 | 2 | |a VVB LAUFERSWEILER Verlag |0 (DE-588)1065553803 |4 pbl | |
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CONTENTS
TABLE OF CONTENTS PAGE
LIST OF FIGURES V
LIST OF TABLES VI
LIST OF ABBREVIATIONS VII
1. INTRODUCTION 1
1.1 DEFINITIONS 1
1.1.1 COPD 1
1.1.2 CHRONIC BRONCHITIS 2
1.1.3 SMALL AIRWAYS DISEASE 2
1.1.4 EMPHYSEMA 3
1.1.5 PULMONARY HYPERTENSION 3
1.1.6 EPIDEMIOLOGY - PREVALENCE - INCIDENCE 3
1.2 COPD CLINICAL MANIFESTATIONS 4
1.2.1 COUGH AND SPUTUM 4
1.2.2 DYSPNEA 4
* 1.2.3 SYSTEMIC MANIFESTATIONS 5
1.3 RISK FACTORS 6
1.3.1 HOST FACTORS 6
1.3.1.1 GENETIC FACTORS 6
1.3.1.2 AIRWAY HYPERRESPONSIVENESS 6
1.3.1.3 GENDER 7
1.3.2 ENVIRONMENTAL FACTORS 7
1.3.2.1 CIGARETTE SMOKE 7
1.3.2.2 AIR POLLUTION 8
1.3.2.3 OCCUPATIONAL EXPOSURES 9
1.3.2.4 OTHER FACTORS 9
1.4 PATHOPHYSIOLOGY OF COPD 9
1.4.1 LUNG INFLAMMATION 9
1.4.2 PROTEASE/ANTI-PROTEINASE BALANCE 13
OTHER PROTEASES 15
METALLOPROTEASES 15
1.4.3 OXIDATIVE/NITROSATIVE STRESS 16
1.4.4 APOPTOSIS 18
1.5 COPD IN OTHER ANIMAL SPECIES 20
IN HORSES 20
IN DOGS AND CATS 21
I
HTTP://D-NB.INFO/1071411357
CONTENTS
1.6 SESTRIN 2 21
1.7 EMPHYSEMA MODELS 27
1.7.1 CIGARETTE SMOKE-INDUCED EMPHYSEMA 27
1.7.2 ELASTASE-INDUCED EMPHYSEMA 28
2. AIMS OF THE STUDY 31
3. MATERIALS 32
3.1 SOLUTIONS AND SUBSTANCES 32
3.2 CONSUMABLES 33
3.3 HEMODYNAMICS-LUNG FUNCTION SETUP 34
3.4 HISTOLOGY 35
3.4.1 EQUIPMENT 35
3.4.2. CONSUMABLES 36
3.5 SMOKE GENERATION AND EXPOSURE SYSTEM 36
3.6 ROS MEASUREMENTS 37
3.7 CELL CULTURE .'. 37
4. METHODS 38
4.1 ANIMALS 38
4.1.1 APPROVALS FOR THE EXPERIMENTS 38
4.1.2 SESTRIN 2 KO MICE 38
4.1.3 HOUSING 38
4.1.4 SESTRIN 2 STUDY/SMOKE EXPOSURE MICE GROUPS: 39
4.1.5 SESTRIN 2 STUDY MICE GROUPS: ELASTASE-INDUCED EMPHYSEMA 39
4.2 EXPERIMENTAL DESIGNS 39
4.2.1.EXPERIMENTAL DESIGN OF TOBACCO SMOKE EXPOSURE OF RRJ141 MICE 39
4.2.2 EXPERIMENTAL DESIGN OF ELASTASE-INDUCED EMPHYSEMA IN RRJ141 MICE
40
4.2.3 ELASTASE INTRATRACHEAL INSTILLATION IN MICE 41
ELASTASE 42
ANAESTHESIA AND ELASTASE INSTILLATION 43
4.3 IN VIVO INVESTIGATIONS 44
4.3.1 ANAESTHESIA AND MOUSE PREPARATION 44
4.3.2 LUNG FUNCTION TESTS 44
4.3.3 HEMODYNAMIC MEASUREMENTS 45
4.4 ALVEOLAR MORPHOMETRY 46
4.5 IMMUNOHISTOCHEMISTRY AND IMMUNOFLUORESCENCE 49
II
CONTENTS
4.6 HEART PREPARATION AND HEART RATIO CALCULATION 50
4.7 QUANTIFICATION OF LUNG ELASTIN BY IMAGE ANALYSIS (SESTRIN 2 MICE
SMOKE EXPOSURE
EXPERIMENT) 51
4.8 RT-PCR 52
4.9 WESTERN BLOTTING 53
4.10 CELL CULTURES AND PREPARATION OF CONDITIONED MEDIA 54
4.11 ROS MEASUREMENTS 55
4.12 STATISTICAL ANALYSES 55
5. RESULTS J 56
5.1 REGULATION OF SESTRIN 2 AND PDGFRP MRNA IN LUNGS OF MICE BY SMOKE
EXPOSURE 56
5.2 SESTRIN 2 INACTIVATION PROTECTS MICE FROM SMOKE-INDUCED EMPHYSEMA 57
5.2.1 SESTRIN 2 INACTIVATION PROTECTS FROM A DECLINE IN LUNG FUNCTION IN
SMOKE-EXPOSED MICE 57
5.2.2 SESTRIN 2 INACTIVATION PROTECTS FROM THE DEVELOPMENT OF PULMONARY
EMPHYSEMA IN SMOKE-
EXPOSED MICE 58
5.2.3 SMOKE EXPOSURE DOES NOT RESULT IN THE DEVELOPMENT OF PULMONARY
HYPERTENSION AND RIGHT
HEART HYPERTROPHY IN SESTRIN 2 KNOCKOUT MICE 61
5.2.4 INACTIVATION OF SESTRIN PRESERVES THE NUMBER OF INTACT ELASTIN
FIBERS PER AREA IN THE LUNGS OF
SMOKE-EXPOSED MICE 62
5.3 RESULTS OF THE INVESTIGATIONS OF THE ROLE OF PDGFRP IN
ELASTASE-INDUCED EMPHYSEMA IN
SESTRIN 2 KNOCKOUT MICE 83
5.3.1 INHIBITION OF PDGFRP ACCENTUATES THE DECLINE IN LUNG FUNCTION OF
SESTRIN 2 KNOCKOUT MICE
TREATED WITH ELASTASE 64
5.3.2 INHIBITION OF PDGFRP WORSENS THE EMPHYSEMA OF SESTRIN 2 KNOCKOUT
MICE TREATED WITH
ELASTASE 64
5.3.3 EFFECT OF THE INHIBITION OF PDGFRP IN HEMODYNAMICS OF
ELASTASE-INDUCED EMPHYSEMA IN
WILD TYPE AND SESTRIN 2 KNOCKOUT MICE 68
5.4 SESTRIN2 INACTIVATION LEADS TO INCREASED PROLIFERATION AND DECREASED
APOPTOSIS IN ALVEOLAR
WALL ATII CELLS 69
5.5 PDGFRP SIGNALING CONTRIBUTES TO LUNG MAINTENANCE THROUGH THE
INDUCTION OF KGF 72
5.5 SUPEROXIDE ANIONS ARE REQUIRED FOR THE INDUCTION OF PDGRP SIGNALING
72
6. DISCUSSION 74
6.1 THE MOUSE MODEL OF SMOKE-INDUCED EMPHYSEMA 74
6.2 STRUCTURAL AND FUNCTIONAL CHANGES IN WILD TYPE MICE AFTER SMOKE
EXPOSURE 76
6.3 SESTRIN 2 KNOCKOUT MICE DID NOT EXHIBIT THE SAME FUNCTIONAL AND
STRUCTURAL CHANGES AS WILD
TYPE MICE AFTER SMOKE EXPOSURE 80
III
CONTENTS
6.4 CIGARETTE SMOKE EXPOSURE CAUSED PULMONARY HYPERTENSION AND RIGHT
HEART HYPERTROPHY IN
WT BUT NOT IN THE SESTRIN 2 KO MICE 83
6.5 SESTRIN 2 IS A REPRESSOR OF PDGFRP SIGNALING AND ALVEOLAR
MAINTENANCE PROGRAMS 84
6.6 CONCLUSION 85
8. SUMMARY 87
9. ZUSAMMENFASSUNG 89
10. BIBLIOGRAPHY 91
11. DECLARATION 144
12. ACKNOWLEDGEMENTS 145
14. PUBLICATIONS 147
RV |
| any_adam_object | 1 |
| author | Fysikopoulos, Athanasios |
| author_GND | (DE-588)1079941282 |
| author_facet | Fysikopoulos, Athanasios |
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| building | Verbundindex |
| bvnumber | BV043375655 |
| ctrlnum | (OCoLC)956554313 (DE-599)DNB1071411357 |
| discipline | Medizin |
| edition | 1. Auflage |
| format | Thesis Book |
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| spelling | Fysikopoulos, Athanasios Verfasser (DE-588)1079941282 aut The role of the antioxidant protein sestrin 2 in emphysema development in mice submitted by Athanasios Fysikopoulos, Veterinarian from Athens, Greece 1. Auflage Gießen VVB Laufersweiler Verlag 2015 XII, 148 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Justus-Liebig-Universität Gießen 2015 protein cabt mice cabt Laporatory mammals cabt antioxidant properties cabt pulmonary emphysema cabt respiratory diseases cabt chronic obstructive pulmonary disease cabt Aktuelle wissenschaftliche Publikation aus dem Bereich der Universitäten. (DE-588)4113937-9 Hochschulschrift gnd-content VVB LAUFERSWEILER Verlag (DE-588)1065553803 pbl Erscheint auch als Online-Ausgabe Fysikopoulos, Athanasios The role of the antioxidant protein sestrin 2 in emphysema development in mice B:DE-101 application/pdf http://d-nb.info/1071411357/04 Inhaltsverzeichnis X:MVB text/html http://deposit.dnb.de/cgi-bin/dokserv?id=5273283&prov=M&dok_var=1&dok_ext=htm Inhaltstext DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028794483&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Fysikopoulos, Athanasios The role of the antioxidant protein sestrin 2 in emphysema development in mice protein cabt mice cabt Laporatory mammals cabt antioxidant properties cabt pulmonary emphysema cabt respiratory diseases cabt chronic obstructive pulmonary disease cabt |
| subject_GND | (DE-588)4113937-9 |
| title | The role of the antioxidant protein sestrin 2 in emphysema development in mice |
| title_auth | The role of the antioxidant protein sestrin 2 in emphysema development in mice |
| title_exact_search | The role of the antioxidant protein sestrin 2 in emphysema development in mice |
| title_full | The role of the antioxidant protein sestrin 2 in emphysema development in mice submitted by Athanasios Fysikopoulos, Veterinarian from Athens, Greece |
| title_fullStr | The role of the antioxidant protein sestrin 2 in emphysema development in mice submitted by Athanasios Fysikopoulos, Veterinarian from Athens, Greece |
| title_full_unstemmed | The role of the antioxidant protein sestrin 2 in emphysema development in mice submitted by Athanasios Fysikopoulos, Veterinarian from Athens, Greece |
| title_short | The role of the antioxidant protein sestrin 2 in emphysema development in mice |
| title_sort | the role of the antioxidant protein sestrin 2 in emphysema development in mice |
| topic | protein cabt mice cabt Laporatory mammals cabt antioxidant properties cabt pulmonary emphysema cabt respiratory diseases cabt chronic obstructive pulmonary disease cabt |
| topic_facet | protein mice Laporatory mammals antioxidant properties pulmonary emphysema respiratory diseases chronic obstructive pulmonary disease Hochschulschrift |
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