Mitochondrial unfolded protein response in the epithelium: relevance to intestinal inflammation
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis Book |
| Language: | English |
| Published: |
München
Dr. Hut
2012
|
| Edition: | 1. Aufl. |
| Series: | Biologie
|
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zsfassung in dt. Sprache |
| Physical Description: | 153 S. graph. Darst. 210 mm x 148 mm, 205 g |
| ISBN: | 9783843903462 3843903468 |
Staff View
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Record in the Search Index
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| adam_text | IMAGE 1
TABLE OF CONTENTS
TABLE OF CONTENTS
ZUSAMMENFASSUNG 3
ABSTRACT 4
TABLE OF CONTENTS 7
1 INTRODUCTION 11
1.1 INFLAMMATORY BOWEL DISEASES 11
1.2 UNFOLDED PROTEIN RESPONSES 12
1.3 ER UNFOLDED PROTEIN RESPONSE 14
1.3.1. ER UPR AND INFLAMMATION 17
1.3.2. ER UPR AND AUTOPHAGY 18
1.3.3. ER UPR AND APOPTOSIS 19
1.3.4. ER UPR AND METABOLISM 20
1.3.5. ER UPR AND IBD 22
1.4 MITOCHONDRIAL DYNAMICS 23
1.4.1. MITOCHONDRIAL PROTEIN HOMEOSTASIS 23
1.4.2. MITOCHONDRIAL UNFOLDED PROTEIN RESPONSE 24
1.4.3. MITOCHONDRIAL BIOGENESIS AND MITOPHAGY 26
1.5 ER-MITOCHONDRIAL NETWORK 28
2 AIMS OF THE WORK 31
3 MATERIAL AND METHODS 33
3.1 ANIMALS 33
3.1.1. ADOPTIVE CD4* T CELL TRANSFER 33
3.1.2. BACTERIAL MONO- AND DUAL-ASSOCIATION 34
3.1.3. DSS-INDUCED COLITIS 34
3.1.4. ASSESSMENT OF BARRIER FUNCTION (USSING CHAMBER) 35
3.1.5. HISTOLOGICAL SCORING 35
3.1.6. ISOLATION OF PRIMARY MOUSE IEC 36
3.2 PATIENTS 36
3.2.1. ISOLATION OF PRIMARY HUMAN IEC 36
3.3 IMMUNOHISTOCHEMICAL LABELING AND QUANTIFICATION 37
3.4 PROTEIN EXPRESSION PROFILING 37
3.4.1. 2D SDS-PAGE 37
3.4.2. TRYPSIN DIGESTION OF PROTEIN SPOTS AND MALDI-TOF-MS 38
3.5 GENE EXPRESSION PROFILING 38
3.6 BIBLIOMETRIC ANALYSIS 40
7
HTTP://D-NB.INFO/1020375507
IMAGE 2
TABLE OF CONTENTS
3.7 CELL CULTURE, TRANSFECTION AND STIMULATION 40
3.8 MITOCHONDRIAL ISOLATION 41
3.9 WESTERN BLOT ANALYSIS 41
3.10 CO-IMMUNOPRECIPITATION 42
3.11 CHROMATIN IMMUNOPRECIPITATION 42
3.12 DNA/RNA ISOLATION, REVERSE TRANSCRIPTION AND REAL-TIME PCR 43
3.13 STATISTICAL ANALYSIS 44
4 RESULTS 45
4.1 MARKERS OF ER- AND MITOCHONDRIAL STRESS ARE INDUCED IN IEC UNDER
INFLAMMATORY CONDITIONS.... 45
4.1.1. PROTEIN EXPRESSION PROFILING OF IEC LINKS ER- AND MITOCHONDRIAL
STRESS IN EXPERIMENTAL COLITIS . 45
4.1.2. ER CHAPERONE GRP78, MITOCHONDRIAL CPN60 AND PKR ARE INDUCED IN
IEC IN EXPERIMENTAL
COLITIS 49
4.1.3. ER CHAPERONE GRP78, MITOCHONDRIAL CPN60 AND PKR ARE INDUCED IN
IEC FROM IBD PATIENTS
51
4.1.4. AUTOPHAGY IS INDUCED IN IEC IN EXPERIMENTAL COLITIS 53
4.2 MITOCHONDRIAL UNFOLDED PROTEIN RESPONSE IN THE IEC LINE MODE-K 54
4.2.1. TRUNCATED ORNITHINE TRANSCARBAMYLASE INDUCES MTUPR IN IEC 54
4.2.2. MITOCHONDRIAL UPR INTEGRATES INTO ER UPR-SIGNALING 55
4.2.3. MITOCHONDRIAL UPR-SIGNALING EMPLOYS PKR 56
4.2.4. MITOCHONDRIAL UPR DOES NOT INDUCE ATF4 58
4.2.5. MITOCHONDRIAL UPR INDUCES AKT PHOSPHORYLATION 59
4.2.6. MITOCHONDRIAL UPR-MEDIATED PKR-INDUCTION IS CA 2* AND PACT
INDEPENDENT 59
4.2.7. MITOCHONDRIAL UPR SIGNALING IS DEPENDENT ON PKR 60
4.2.8. MITOCHONDRIAL UPR INDUCES AUTOPHAGY 62
4.3 PKR MICE 63
4.3.1. PKR MICE DISPLAY ENHANCED COLONIC BARRIER FUNCTION AND
INCREASED MITOCHONDRIAL MARKERS 63
4.3.2. PKR MICE SHOW REDUCED SENSITIVITY TO DSS-INDUCED COLITIS 64
4.3.3. MITOCHONDRIAL ABUNDANCE DECLINES IN PKR MICE UPON
DSS-TREATMENT 66
4.4 GENE EXPRESSION PROFILING OF IEC AS TOOL TO IDENTIFY NOVEL TARGET
PROTEINS/SIGNALING PATHWAYS IN
INTESTINAL INFLAMMATION 69
4.4.1. MOST HIGHLY REGULATED GENES IN IEC IN RESPONSE TO CD4* T CELL
TRANSFER 72
4.4.2. DATA ANALYSIS OF REGULATED GENES IN IEC IN RESPONSE TO CD4* T
CELL TRANSFER 79
4.4.3. GENES BEST CORRELATED TO THE HISTOLOGICAL SCORE IN IEC UPON CD4*
T CELL TRANSFER 86
4.4.4. GENES BEST CORRELATED TO THE PRESENCE OF IL-10 IN IEC UNDER
NON-INFLAMMATORY CONDITIONS. 93
5 DISCUSSION 95
5.1 PKR 95
8
IMAGE 3
TABLE OF CONTENTS
5.2 MITOCHONDRIAL UPR SIGNALING 96
5.3 PKR MICE 98
5.4 MITOCHONDRIA AS INTEGRATORS OF CELLULAR DANGER SIGNALING 99
5.5 ER UPR AND MITOCHONDRIAL DYSFUNCTION IN IBD 100
5.6 SCREENING FOR POTENTIAL NEW TARGET GENES AND CELLULAR PATHWAYS 102
5.7 CONCLUSION AND PERSPECTIVE 104
6 APPENDIX 107
LIST OF FIGURES 129
LIST OF TABLES 131
ABBREVIATIONS 133
REFERENCES 135
PUBLICATIONS AND PRESENTATIONS 145
ACKNOWLEDGEMENTS 151
CURRICULUM VITAE 153
9
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| any_adam_object | 1 |
| author | Rath, Eva |
| author_facet | Rath, Eva |
| author_role | aut |
| author_sort | Rath, Eva |
| author_variant | e r er |
| building | Verbundindex |
| bvnumber | BV040106661 |
| classification_tum | BIO 770d MED 430d CHE 880d |
| ctrlnum | (OCoLC)796206339 (DE-599)DNB1020375507 |
| dewey-full | 616.344071 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 616 - Diseases |
| dewey-raw | 616.344071 |
| dewey-search | 616.344071 |
| dewey-sort | 3616.344071 |
| dewey-tens | 610 - Medicine and health |
| discipline | Biologie Chemie Medizin |
| edition | 1. Aufl. |
| format | Thesis Book |
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| genre_facet | Hochschulschrift |
| id | DE-604.BV040106661 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T00:17:00Z |
| institution | BVB |
| isbn | 9783843903462 3843903468 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-024963091 |
| oclc_num | 796206339 |
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| owner_facet | DE-12 DE-19 DE-BY-UBM DE-91 DE-BY-TUM DE-M49 DE-BY-TUM |
| physical | 153 S. graph. Darst. 210 mm x 148 mm, 205 g |
| publishDate | 2012 |
| publishDateSearch | 2012 |
| publishDateSort | 2012 |
| publisher | Dr. Hut |
| record_format | marc |
| series2 | Biologie |
| spelling | Rath, Eva Verfasser aut Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation Eva Rath 1. Aufl. München Dr. Hut 2012 153 S. graph. Darst. 210 mm x 148 mm, 205 g txt rdacontent n rdamedia nc rdacarrier Biologie Zsfassung in dt. Sprache Zugl.: München, Techn. Univ., Diss., 2012 Mitochondria (DE-588)249534-X gnd rswk-swf Genexpression (DE-588)4020136-3 gnd rswk-swf Unfolded Proteins (DE-588)4730138-7 gnd rswk-swf Signaltransduktion (DE-588)4318717-1 gnd rswk-swf Chronische Darmentzündung (DE-588)4273697-3 gnd rswk-swf Stressreaktion (DE-588)4138565-2 gnd rswk-swf Mitochondrium (DE-588)4124939-2 gnd rswk-swf Proteinfaltung (DE-588)4324567-5 gnd rswk-swf Darmepithel (DE-588)4220708-3 gnd rswk-swf Epithelzelle (DE-588)4259648-8 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Chronische Darmentzündung (DE-588)4273697-3 s Darmepithel (DE-588)4220708-3 s Mitochondrium (DE-588)4124939-2 s Proteinfaltung (DE-588)4324567-5 s Stressreaktion (DE-588)4138565-2 s Signaltransduktion (DE-588)4318717-1 s DE-604 Epithelzelle (DE-588)4259648-8 s Mitochondria (DE-588)249534-X f Genexpression (DE-588)4020136-3 s Unfolded Proteins (DE-588)4730138-7 s b DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024963091&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Rath, Eva Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation Mitochondria (DE-588)249534-X gnd Genexpression (DE-588)4020136-3 gnd Unfolded Proteins (DE-588)4730138-7 gnd Signaltransduktion (DE-588)4318717-1 gnd Chronische Darmentzündung (DE-588)4273697-3 gnd Stressreaktion (DE-588)4138565-2 gnd Mitochondrium (DE-588)4124939-2 gnd Proteinfaltung (DE-588)4324567-5 gnd Darmepithel (DE-588)4220708-3 gnd Epithelzelle (DE-588)4259648-8 gnd |
| subject_GND | (DE-588)249534-X (DE-588)4020136-3 (DE-588)4730138-7 (DE-588)4318717-1 (DE-588)4273697-3 (DE-588)4138565-2 (DE-588)4124939-2 (DE-588)4324567-5 (DE-588)4220708-3 (DE-588)4259648-8 (DE-588)4113937-9 |
| title | Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation |
| title_auth | Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation |
| title_exact_search | Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation |
| title_full | Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation Eva Rath |
| title_fullStr | Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation Eva Rath |
| title_full_unstemmed | Mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation Eva Rath |
| title_short | Mitochondrial unfolded protein response in the epithelium |
| title_sort | mitochondrial unfolded protein response in the epithelium relevance to intestinal inflammation |
| title_sub | relevance to intestinal inflammation |
| topic | Mitochondria (DE-588)249534-X gnd Genexpression (DE-588)4020136-3 gnd Unfolded Proteins (DE-588)4730138-7 gnd Signaltransduktion (DE-588)4318717-1 gnd Chronische Darmentzündung (DE-588)4273697-3 gnd Stressreaktion (DE-588)4138565-2 gnd Mitochondrium (DE-588)4124939-2 gnd Proteinfaltung (DE-588)4324567-5 gnd Darmepithel (DE-588)4220708-3 gnd Epithelzelle (DE-588)4259648-8 gnd |
| topic_facet | Mitochondria Genexpression Unfolded Proteins Signaltransduktion Chronische Darmentzündung Stressreaktion Mitochondrium Proteinfaltung Darmepithel Epithelzelle Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=024963091&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT ratheva mitochondrialunfoldedproteinresponseintheepitheliumrelevancetointestinalinflammation |