Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation:
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| 245 | 1 | 0 | |a Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |c von M.Sc. Joel Filipe Garcia Guerra |
| 264 | 1 | |a Jena |c [2022] | |
| 300 | |a XIII, 131 Seiten |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
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| 502 | |b Dissertation |c Friedrich-Schiller-Universität Jena |d 2022 | ||
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Datensatz im Suchindex
| _version_ | 1804185059732750336 |
|---|---|
| adam_text | TABLE
OF
CONTENTS
1.
INTRODUCTION
....................................................................................................................................
1
1.1
.
METABOLISM
.....................................................................................................................
1
1.1.1
PENTOSE
PHOSPHATE
PATHWAY
........................................................................................
3
1.1.2
NICOTINAMIDE
ADENINE
DINUCLEOTIDE
PHOSPHATE
..........................................................4
1.1.3
GLUTATHIONE
SYSTEM
........................................................................................................
5
1.2
INFLAMMATION
..........................................................................................................................
6
1.3
IMMUNOMETABOLISM
..............................................................................................................
7
1.3.1
WARBURG
EFFECT
IN
IMMUNITY
..........................................................................................
9
1.4
DISEASE
TOLERANCE
...............................................................................................................
11
1.4.1
THERMOREGULATION
........................................................................................................
12
1.4.2
IRON
REGULATION
...............................................................................................................
13
1.5
TISSUE
DAMAGE
CONTROL
......................................................................................................
14
1.5.1
ENERGY
REGULATION
........................................................................................................
15
1.5.2
NRF2
MASTER
REGULATOR
...............................................................................................
16
1.6
HEME
....................................................................................................................................
18
1.6.1
HEME
BIOSYNTHESIS
....................................................................................................
18
1.6.2
HEME
TOXICITY
..............................................................................................................
19
1.7
HEMOLYSIS
............................................................................................................................
21
1.7.1
HEMOLYSIS-INDUCED
KIDNEY
DAMAGE
........................................................................
22
1.8
HEME
OXYGENASE
................................................................................................................
23
1.8.1
HEME
OXYGENASE
1
REGULATION
.................................................................................
25
1.8.2
HEME
OXYGENASE
DELETION
........................................................................................
27
1.8.3
HEME
OXYGENASE
ASSOCIATED
DISORDERS
.................................................................
28
2.
SCIENTIFIC
AIMS
.............................................................................................................................
30
3.
MATERIALS
AND
METHODS
...............................................................................................................
31
3.1
ANIMAL
CARE
..........................................................................................................................34
3.2
INDUCIBLE
GENE
DELETION
......................................................................................................
35
3.3
INTRAVASCULAR
HEMOLYSIS
.....................................................................................................35
3.4
STAPHYLOCOCCUS
AUREUS
INFECTION
......................................................................................35
3.5
IN
VIVO
EXPERIMENTS
............................................................................................................
35
3.6
ANTIBODY-MEDIATED
DEPLETION
OF
GR1
+
CELLS
...................................................................36
3.7
MAGNETIC
RESONANCE
IMAGING
............................................................................................36
3.8
PROMETHION
BEHAVIORAL
AND
PHENOTYPING
SYSTEM
...........................................................
37
3.9
GLUCOSE,
ALANINE,
GLUTAMINE,
AND
INSULIN
TOLERANCE
TESTS
.............................................38
3.10
SEROLOGY
..............................................................................................................................38
3.11
HISTOLOGY
..............................................................................................................................38
3.12
TARGETED
METABOLOMICS
....................................................................................................
39
3.13
METABOLOMIC
PATHWAY
ANALYSIS
........................................................................................
39
3.14
IN
SILICA
ANALYSIS
OF
TARGETED
METABOLOMICS
...................................................................
39
3.15
RNA
SEQUENCING
................................................................................................................
40
3.16
RNA
SEQUENCING
ANALYSIS
.................................................................................................
40
3.17
TETRAPYRROLE
PREPARATION
...................................................................................................
41
3.18
CELL
TREATMENT
.....................................................................................................................
41
3.19
CELL
CULTURE
INFECTION
MODEL
..............................................................................................
41
3.20
IMKC
HMOX1
CRISPR-CAS9
KNOCKOUT
CELL
LINE
............................................................
42
3.21
FLOW
CYTOMETRY
...................................................................................................................
42
3.22
IMMUNOBLOTTING
...................................................................................................................
43
3.23
REVERSE
TRANSCRIPTASE
-
QUANTITATIVE
PCR
...................................................................
43
3.24
CELL
CYCLE
ANALYSIS
.............................................................................................................
44
3.25
CYTOKINE
MEASUREMENTS
...................................................................................................
44
3.26
PHAGOCYTOSIS
ASSAY
..........................................................................................................
44
3.27
LIPID
PEROXIDATION
ASSAY
...................................................................................................
45
3.28
MEASUREMENT
OF
MITOCHONDRIAL
REACTIVE
OXYGEN
SPECIES
(ROS)
AND
MITOCHONDRIAL
MEMBRANE
POTENTIAL
.......................................................................................................................
45
3.29
SEAHORSE
ANALYSIS
.............................................................................................................
45
3.30
STATISTICAL
ANALYSIS
.............................................................................................................
45
4.
RESULTS
........................................................................................................................................
47
4.1
HO-1
REGULATES
CENTRAL
CARBON
METABOLISM
...................................................................
47
4.1.1
LABILE
HEME
INDUCES
CHANGES
IN
METABOLISM
..........................................................
47
4.1.2
EFFECTS
OF
INDUCING
A
HMOXI
CONDITIONAL
DELETION
...................................................
49
4.1.3
IMPACT
OF
INDUCIBLE
HMOX1
DELETION
ON
INFECTION
AND
INFLAMMATORY
STRESS
.........
55
4.1.4
HMOX1
EXPRESSION
AFFORDS
ADAPTATION
TO
INTRAVASCULAR
HEMOLYSIS
.......................
57
4.1.5
LABILE
HEME
REITERATES
INTRAVASCULAR
ASSOCIATED
DAMAGE
......................................
58
4.1.6
HO-1
MODULATES
IMMUNE
RESPONSE
AND
IS
PROTECTIVE
AGAINST
LABILE
HEME
INDUCED
KIDNEY
DAMAGE
.............................................................................................................
61
4.1.7
HEME
INDUCED
MORTALITY
IS
INDEPENDENT
OF
INFLAMMATION-DRIVEN
TISSUE
DAMAGE63
4.1.8
HO-1
REGULATES
ENERGY
METABOLISM
IN
ADAPTATION
TO
HEME
STIMULUS
...................
65
XII
4.2
HO-1
EXPRESSION
IMPACT
KUPFFER
CELL
PROTECTION
AGAINST
HEME
BUT
NOT
ITS
IMMUNE
RESPONSE
.........................................................................................................................................70
4.2.1
HO-1
EXPRESSION
PREVENTS
LIPID
PEROXIDATION
..........................................................
71
4.2.2
HO-1
DELETION
AFFECTS
GENE
TRANSCRIPTION
OF
STRESS
RESPONSE
...............................74
4.2.3
HO-1
DELETION
DOES
NOT
IMPAR
INFLAMMATORY
RESPONSE
IN
KC
...............................75
4.2.4
HO-1
EXPRESSION
PROMOTES
KC
SURVIVAL
TO
S.
AUREUS
INFECTION
.............................76
5.
DISCUSSION
...................................................................................................................................
79
6.
CONCLUSION
...................................................................................................................................92
7.
REFERENCES
..................................................................................................................................
93
8.
APPENDIX
....................................................................................................................................
110
9.
LIST
OF
FIGURES
............................................................................................................................
119
10.
EHRENWORTLICHE
ERKLARUNG
......................................................................................................
127
11.
T
EILPUBLIKATION
.......................................................................................................................
128
12.
ACKNOWLEDGEMENTS
..............................................................................................................
129
13.
LEBENSLAUF
.............................................................................................................................
130
XIII
|
| adam_txt |
TABLE
OF
CONTENTS
1.
INTRODUCTION
.
1
1.1
.
METABOLISM
.
1
1.1.1
PENTOSE
PHOSPHATE
PATHWAY
.
3
1.1.2
NICOTINAMIDE
ADENINE
DINUCLEOTIDE
PHOSPHATE
.4
1.1.3
GLUTATHIONE
SYSTEM
.
5
1.2
INFLAMMATION
.
6
1.3
IMMUNOMETABOLISM
.
7
1.3.1
WARBURG
EFFECT
IN
IMMUNITY
.
9
1.4
DISEASE
TOLERANCE
.
11
1.4.1
THERMOREGULATION
.
12
1.4.2
IRON
REGULATION
.
13
1.5
TISSUE
DAMAGE
CONTROL
.
14
1.5.1
ENERGY
REGULATION
.
15
1.5.2
NRF2
MASTER
REGULATOR
.
16
1.6
HEME
.
18
1.6.1
HEME
BIOSYNTHESIS
.
18
1.6.2
HEME
TOXICITY
.
19
1.7
HEMOLYSIS
.
21
1.7.1
HEMOLYSIS-INDUCED
KIDNEY
DAMAGE
.
22
1.8
HEME
OXYGENASE
.
23
1.8.1
HEME
OXYGENASE
1
REGULATION
.
25
1.8.2
HEME
OXYGENASE
DELETION
.
27
1.8.3
HEME
OXYGENASE
ASSOCIATED
DISORDERS
.
28
2.
SCIENTIFIC
AIMS
.
30
3.
MATERIALS
AND
METHODS
.
31
3.1
ANIMAL
CARE
.34
3.2
INDUCIBLE
GENE
DELETION
.
35
3.3
INTRAVASCULAR
HEMOLYSIS
.35
3.4
STAPHYLOCOCCUS
AUREUS
INFECTION
.35
3.5
IN
VIVO
EXPERIMENTS
.
35
3.6
ANTIBODY-MEDIATED
DEPLETION
OF
GR1
+
CELLS
.36
3.7
MAGNETIC
RESONANCE
IMAGING
.36
3.8
PROMETHION
BEHAVIORAL
AND
PHENOTYPING
SYSTEM
.
37
3.9
GLUCOSE,
ALANINE,
GLUTAMINE,
AND
INSULIN
TOLERANCE
TESTS
.38
3.10
SEROLOGY
.38
3.11
HISTOLOGY
.38
3.12
TARGETED
METABOLOMICS
.
39
3.13
METABOLOMIC
PATHWAY
ANALYSIS
.
39
3.14
IN
SILICA
ANALYSIS
OF
TARGETED
METABOLOMICS
.
39
3.15
RNA
SEQUENCING
.
40
3.16
RNA
SEQUENCING
ANALYSIS
.
40
3.17
TETRAPYRROLE
PREPARATION
.
41
3.18
CELL
TREATMENT
.
41
3.19
CELL
CULTURE
INFECTION
MODEL
.
41
3.20
IMKC
HMOX1
CRISPR-CAS9
KNOCKOUT
CELL
LINE
.
42
3.21
FLOW
CYTOMETRY
.
42
3.22
IMMUNOBLOTTING
.
43
3.23
REVERSE
TRANSCRIPTASE
-
QUANTITATIVE
PCR
.
43
3.24
CELL
CYCLE
ANALYSIS
.
44
3.25
CYTOKINE
MEASUREMENTS
.
44
3.26
PHAGOCYTOSIS
ASSAY
.
44
3.27
LIPID
PEROXIDATION
ASSAY
.
45
3.28
MEASUREMENT
OF
MITOCHONDRIAL
REACTIVE
OXYGEN
SPECIES
(ROS)
AND
MITOCHONDRIAL
MEMBRANE
POTENTIAL
.
45
3.29
SEAHORSE
ANALYSIS
.
45
3.30
STATISTICAL
ANALYSIS
.
45
4.
RESULTS
.
47
4.1
HO-1
REGULATES
CENTRAL
CARBON
METABOLISM
.
47
4.1.1
LABILE
HEME
INDUCES
CHANGES
IN
METABOLISM
.
47
4.1.2
EFFECTS
OF
INDUCING
A
HMOXI
CONDITIONAL
DELETION
.
49
4.1.3
IMPACT
OF
INDUCIBLE
HMOX1
DELETION
ON
INFECTION
AND
INFLAMMATORY
STRESS
.
55
4.1.4
HMOX1
EXPRESSION
AFFORDS
ADAPTATION
TO
INTRAVASCULAR
HEMOLYSIS
.
57
4.1.5
LABILE
HEME
REITERATES
INTRAVASCULAR
ASSOCIATED
DAMAGE
.
58
4.1.6
HO-1
MODULATES
IMMUNE
RESPONSE
AND
IS
PROTECTIVE
AGAINST
LABILE
HEME
INDUCED
KIDNEY
DAMAGE
.
61
4.1.7
HEME
INDUCED
MORTALITY
IS
INDEPENDENT
OF
INFLAMMATION-DRIVEN
TISSUE
DAMAGE63
4.1.8
HO-1
REGULATES
ENERGY
METABOLISM
IN
ADAPTATION
TO
HEME
STIMULUS
.
65
XII
4.2
HO-1
EXPRESSION
IMPACT
KUPFFER
CELL
PROTECTION
AGAINST
HEME
BUT
NOT
ITS
IMMUNE
RESPONSE
.70
4.2.1
HO-1
EXPRESSION
PREVENTS
LIPID
PEROXIDATION
.
71
4.2.2
HO-1
DELETION
AFFECTS
GENE
TRANSCRIPTION
OF
STRESS
RESPONSE
.74
4.2.3
HO-1
DELETION
DOES
NOT
IMPAR
INFLAMMATORY
RESPONSE
IN
KC
.75
4.2.4
HO-1
EXPRESSION
PROMOTES
KC
SURVIVAL
TO
S.
AUREUS
INFECTION
.76
5.
DISCUSSION
.
79
6.
CONCLUSION
.92
7.
REFERENCES
.
93
8.
APPENDIX
.
110
9.
LIST
OF
FIGURES
.
119
10.
EHRENWORTLICHE
ERKLARUNG
.
127
11.
T
EILPUBLIKATION
.
128
12.
ACKNOWLEDGEMENTS
.
129
13.
LEBENSLAUF
.
130
XIII |
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| author_facet | Guerra, Joel 1992- |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
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| id | DE-604.BV048898321 |
| illustrated | Illustrated |
| index_date | 2024-07-03T21:50:08Z |
| indexdate | 2024-07-10T09:49:13Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034162776 |
| oclc_num | 1333689833 |
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| owner_facet | DE-355 DE-BY-UBR |
| physical | XIII, 131 Seiten Illustrationen, Diagramme 30 cm |
| publishDate | 2022 |
| publishDateSearch | 2022 |
| publishDateSort | 2022 |
| record_format | marc |
| spelling | Guerra, Joel 1992- Verfasser (DE-588)123402084X aut Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation von M.Sc. Joel Filipe Garcia Guerra Jena [2022] XIII, 131 Seiten Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Friedrich-Schiller-Universität Jena 2022 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1260073998/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034162776&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p dnb 20221018 DE-101 https://d-nb.info/provenance/plan#dnb 2\p dnb 20221018 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Guerra, Joel 1992- Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |
| subject_GND | (DE-588)4113937-9 |
| title | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |
| title_auth | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |
| title_exact_search | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |
| title_exact_search_txtP | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |
| title_full | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation von M.Sc. Joel Filipe Garcia Guerra |
| title_fullStr | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation von M.Sc. Joel Filipe Garcia Guerra |
| title_full_unstemmed | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation von M.Sc. Joel Filipe Garcia Guerra |
| title_short | Heme oxygenase-1 mediates kidney central carbon metabolism regulation to heme stimulation |
| title_sort | heme oxygenase 1 mediates kidney central carbon metabolism regulation to heme stimulation |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1260073998/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034162776&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT guerrajoel hemeoxygenase1mediateskidneycentralcarbonmetabolismregulationtohemestimulation |
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