Role of PGC-1 alpha and PGC-1 beta in inflammatory processes:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English German |
| Veröffentlicht: |
2014
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. und engl. Sprache |
| Beschreibung: | 138 S. Ill., graph. Darst. |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV042732437 | ||
| 003 | DE-604 | ||
| 005 | 00000000000000.0 | ||
| 007 | t | ||
| 008 | 150804s2014 ad|| m||| 00||| eng d | ||
| 035 | |a (OCoLC)915816902 | ||
| 035 | |a (DE-599)HBZHT018611537 | ||
| 040 | |a DE-604 |b ger |e rakwb | ||
| 041 | 0 | |a eng |a ger | |
| 049 | |a DE-355 |a DE-188 |a DE-83 | ||
| 082 | 0 | |a 610 | |
| 100 | 1 | |a Noe, Natalie |d 1985- |e Verfasser |0 (DE-588)1069801119 |4 aut | |
| 245 | 1 | 0 | |a Role of PGC-1 alpha and PGC-1 beta in inflammatory processes |c vorgelegt von Natalie Isabelle Noe |
| 264 | 1 | |c 2014 | |
| 300 | |a 138 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 500 | |a Zsfassung in dt. und engl. Sprache | ||
| 502 | |a Köln, Univ., Diss., 2014 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m HBZ Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028163435&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-028163435 | ||
Datensatz im Suchindex
| _version_ | 1804174945215840256 |
|---|---|
| adam_text | Titel: Role of PGC-1 alpha and PGC-1 beta in inflammatory processes
Autor: Noe, Natalie Isabelle
Jahr: 2014
Table of contents
Table of contents..................................................................................................4
Abstract.................................................................................................................7
1. Introduction....................................................................................................8
1.1. Neurodegenerative diseases........................................................................8
1.2. Inflammation..................................................................................................8
1.2.1. Neuroinflammation.........................................................................................................9
1.2.2. Molecular pathways of inflammation..............................................................................9
1.2.3. Inflammatory phases and adaptation mechanisms......................................................11
1.2.3.1. Cellular stress response........................................................................................................12
1.2.3.2. Mitochondria in inflammation.................................................................................................12
1.2.3.3. Transcriptional link of cellular adaptation mechanisms to inflammation.................................13
1.3. The PGC-1 transcriptional coactivators....................................................16
1.4. Role of PGC-1 in the brain and the associations with neurodegeneration
and inflammation................................................................................................18
1.4.1. PGC-1 in normal brain function and neurodegeneration..............................................18
1.4.2. PGC-1 in inflammation.................................................................................................21
1.4.2.1. PGC-1 a in inflammation.........................................................................................................21
1.4.2.2. PGC-1 ß in inflammation.........................................................................................................23
1.5. PGC-1a as an indirect drug target.............................................................23
1.5.1. Activation via PPAR agonists.......................................................................................24
1.5.2. Activation via AMPK and Sirtl......................................................................................25
1.6. Aim of the thesis..........................................................................................27
2. Material and Methods..................................................................................28
2.1. Mouse experiments.....................................................................................28
2.1.1. Animal Care..................................................................................................................28
2.1.2. Mouse lines..................................................................................................................28
2.1.2.1. PGC-1 a forebrain KO mice....................................................................................................28
2.1.2.2. PGC-1P forebrain KO mice....................................................................................................29
2.1.3. Isolation of genomic DNA from mouse tails.................................................................29
2.1.4. Isolation of genomic DNA from tissue..........................................................................29
2.1.5. Quantification of nucleic acids......................................................................................29
2.1.6. Genotyping...................................................................................................................30
2.1.7. Tissue-specific KO with CamKlla-Cre..........................................................................30
2.1.8. Injections......................................................................................................................32
2.1.9. Monitoring body weight and body core temperature....................................................32
2.1.10. Intracardial blood collection and perfusion...................................................................33
2.1.11. Serum analysis- Cytokine ELISA.................................................................................33
2.2. Cell Biology....................33
2.2.1. SH-SY5Y cell (ine.........................................................................................................33
2.2.2. Mouse embryonic fibroblasts (MEF).............................................................................34
2.2.3. Pharmaceutical treatments...........................................................................................34
2.2.4. Neurotoxic insult...........................................................................................................35
2.2.5. Cell growth and viability................................................................................................35
2.3. Biochemistry................................................................................................35
2.3.1. Protein isolation from cells and tissue..........................................................................35
2.3.2. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis........................................36
2.3.3. immunobi oiling.............................................................................................................36
2.4. Densitometrie quantification and statistical analysis..............................37
3. Results..........................................................................................................38
3.1. Timeline of inflammatory response and bioenergetics in vivo...............39
3.1.1. Phenotype after a systemic inflammatory insult...........................................................39
3.1.2. Molecular response during acute inflammation............................................................41
Hepatic inflammatory response..................................................................................................................41
Neuroinfiammatory response.....................................................................................................................42
3.1.3. Activation of cell signaling pathways...........................................................................44
3.1.4. Timeline of mitochondria in inflammation.....................................................................46
3.2. Role of PGC-1a and PGC-Iß in inflammation...........................................48
3.2.1. Phenotype of KO mice and Uitermate controls in response to the LPS challenge.......49
3.2.2. Impact of a neuronal PGC-1 deficiency on the molecular neuroinfiammatory and
cellular stress response.................................................................................................................51
PGC-10 KO cohorts...................................................................................................................................51
PGC-1 ß KO cohorts...................................................................................................................................52
3.2.3. Impact of a neuronal PGC-1 deficiency on the brain metabolic adaptation to a systemic
inflammatory insult........................................................................................................................54
3.2.4. Impact of a neuronal PGC-1 deficiency on the cortical mitochondrial profile after a
systemic inflammatory insult.........................................................................................................56
3.2.5. Impact of neuronal PGC-1 deficiency on the inflammatory response in liver..............58
3.3. Therapeutic potential of PGC-1 a activation in pathogenic processes
associated with mitochondrial dysfunction.....................................................60
3.3.1. Pharmaceutical activation of the PGC-1 a pathway in vitro..........................................61
3.3.1.1. Pharmaceutical activation of PGC-1 a in a neuronal cell model.............................................61
3.3.1.2. Effect on the cellular stress response....................................................................................63
3.3.1.3. PGC-1 o-dependent effects on mitochondrial biogenesis and the cellular stress program in
MEFs 66
3.3.2. Impact of bezafibrate pretreatment on cytotoxic insults in SH-SY5Y...........................68
3.3.3. Pharmaceutical activation of the PGC-1 o pathway in vivo..........................................69
3.3.3.1. Tissue-specific activation of the PGC-1 pathway in vivo........................................................70
3.3.3.2. Activation of cellular stress pathways in vivo.........................................................................72
3.3.4. Impact of a bezafibrate pretreatment on a systemic inflammatory insult in vivo..........73
3.3.4.1. Effect of bezafibrate pretreatment on the phenotype of the LPS mouse model.....................74
3.3.4.2. Impact of bezafibrate pretreatment on the acute neuroinfiammatory response.....................76
3.3.4.3. Impact of bezafibrate pretreatment on hepatic inflammatory response.................................78
4. Discussion...................................................................................................81
4.1. Timeline of inflammatory and bioenergetic response..............................81
4.1.1. Phenotype of the LPS model in the acute phase and recovery...................................82
4.1.2. Hepatic inflammatory and cellular stress signaling in the acute phase........................82
4.1.3. Acute neuroinflammatory and cellular stress signaling in the cortex...........................84
4.1.4. Homeostasis and stress adaption in the acute phase..................................................84
4.1.5. Mitochondrial metabolism during the acute phase of inflammation.............................86
4.2. Effect of a neuronal PGC-1 deficiency on (neuro)-inflammation.............88
4.2.1. PGC-1a and PGC-1 ß forebrain deficiency...................................................................91
4.2.2. Impact of a PGC-1 forebrain deficiency on the inflammatory phenotype.....................91
4.2.3. Impact of a PGC-1 forebrain deficiency on neuroinflammation...................................92
4.2.4. Impact of neuronal PGC-1 deficiency on hepatic inflammation...................................94
4.3. In vitro and in vivo action spectrum of PGC-1a inducing pharmaceuticals
96
4.3.1. The dose-effect response.............................................................................................97
4.3.2. Activation of mitochondrial biogenesis.........................................................................97
4.3.3. Activation of stress regulatory pathways......................................................................99
4.4. In vitro and in vivo protective features of bezafibrate in pathogenic
states.................................................................................................................100
4.4.1. Impact of bezafibrate on a neurotoxic insult in neuroblastomas................................100
4.4.2. Impact of bezafibrate on a systemic inflammatory insult............................................101
Modulation of molecular inflammatory and stress pathways...................................................................102
Modulation of mitochondrial biogenesis..................................................................................................103
4.5. Conclusions...............................................................................................104
Zusammenfassung...........................................................................................106
Appendix...........................................................................................................107
References........................................................................................................114
List of abbreviations........................................................................................131
Figure index......................................................................................................133
Table index........................................................................................................135
Acknowledgement............................................................................................136
Eidesstattliche Erklärung................................................................................137
Curriculum vitae........................138
|
| any_adam_object | 1 |
| author | Noe, Natalie 1985- |
| author_GND | (DE-588)1069801119 |
| author_facet | Noe, Natalie 1985- |
| author_role | aut |
| author_sort | Noe, Natalie 1985- |
| author_variant | n n nn |
| building | Verbundindex |
| bvnumber | BV042732437 |
| ctrlnum | (OCoLC)915816902 (DE-599)HBZHT018611537 |
| dewey-full | 610 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 610 - Medicine and health |
| dewey-raw | 610 |
| dewey-search | 610 |
| dewey-sort | 3610 |
| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| format | Thesis Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01152nam a2200301 c 4500</leader><controlfield tag="001">BV042732437</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">00000000000000.0</controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">150804s2014 ad|| m||| 00||| eng d</controlfield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)915816902</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)HBZHT018611537</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield><subfield code="a">ger</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-355</subfield><subfield code="a">DE-188</subfield><subfield code="a">DE-83</subfield></datafield><datafield tag="082" ind1="0" ind2=" "><subfield code="a">610</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Noe, Natalie</subfield><subfield code="d">1985-</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)1069801119</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Role of PGC-1 alpha and PGC-1 beta in inflammatory processes</subfield><subfield code="c">vorgelegt von Natalie Isabelle Noe</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">138 S.</subfield><subfield code="b">Ill., graph. Darst.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">Zsfassung in dt. und engl. Sprache</subfield></datafield><datafield tag="502" ind1=" " ind2=" "><subfield code="a">Köln, Univ., Diss., 2014</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="0">(DE-588)4113937-9</subfield><subfield code="a">Hochschulschrift</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">HBZ Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028163435&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-028163435</subfield></datafield></record></collection> |
| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
| genre_facet | Hochschulschrift |
| id | DE-604.BV042732437 |
| illustrated | Illustrated |
| indexdate | 2024-07-10T07:08:27Z |
| institution | BVB |
| language | English German |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-028163435 |
| oclc_num | 915816902 |
| open_access_boolean | |
| owner | DE-355 DE-BY-UBR DE-188 DE-83 |
| owner_facet | DE-355 DE-BY-UBR DE-188 DE-83 |
| physical | 138 S. Ill., graph. Darst. |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| record_format | marc |
| spelling | Noe, Natalie 1985- Verfasser (DE-588)1069801119 aut Role of PGC-1 alpha and PGC-1 beta in inflammatory processes vorgelegt von Natalie Isabelle Noe 2014 138 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. und engl. Sprache Köln, Univ., Diss., 2014 (DE-588)4113937-9 Hochschulschrift gnd-content HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028163435&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Noe, Natalie 1985- Role of PGC-1 alpha and PGC-1 beta in inflammatory processes |
| subject_GND | (DE-588)4113937-9 |
| title | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes |
| title_auth | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes |
| title_exact_search | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes |
| title_full | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes vorgelegt von Natalie Isabelle Noe |
| title_fullStr | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes vorgelegt von Natalie Isabelle Noe |
| title_full_unstemmed | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes vorgelegt von Natalie Isabelle Noe |
| title_short | Role of PGC-1 alpha and PGC-1 beta in inflammatory processes |
| title_sort | role of pgc 1 alpha and pgc 1 beta in inflammatory processes |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=028163435&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT noenatalie roleofpgc1alphaandpgc1betaininflammatoryprocesses |