Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Karlsruhe
FZKA
2002
|
| Ausgabe: | Als Ms. gedr. |
| Schriftenreihe: | Wissenschaftliche Berichte / Forschungszentrum Karlsruhe Technik und Umwelt
6806 |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zugl.: Karlsruhe, Univ., Diss., 2002 |
| Beschreibung: | XI, 127 S. Ill., graph. Darst. : 30 cm |
Internformat
MARC
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| 001 | BV016975273 | ||
| 003 | DE-604 | ||
| 005 | 20040130 | ||
| 007 | t | ||
| 008 | 030311s2002 gw ad|| tm|| 00||| eng d | ||
| 016 | 7 | |a 966498925 |2 DE-101 | |
| 035 | |a (OCoLC)76726870 | ||
| 035 | |a (DE-599)BVBBV016975273 | ||
| 040 | |a DE-604 |b ger |e rakddb | ||
| 041 | 0 | |a eng | |
| 044 | |a gw |c DE | ||
| 049 | |a DE-12 |a DE-91 | ||
| 088 | |a FZKA 6806 | ||
| 100 | 1 | |a Zhu, Ping |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |c Ping Zhu. Forschungszentrum Karlsruhe GmbH, Karlsruhe |
| 246 | 1 | 3 | |a Valproic acid and peroxisome proliferator-activated receptor delta are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| 250 | |a Als Ms. gedr. | ||
| 264 | 1 | |a Karlsruhe |b FZKA |c 2002 | |
| 300 | |a XI, 127 S. |b Ill., graph. Darst. : 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 1 | |a Wissenschaftliche Berichte / Forschungszentrum Karlsruhe Technik und Umwelt |v 6806 | |
| 500 | |a Zugl.: Karlsruhe, Univ., Diss., 2002 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 810 | 2 | |a Forschungszentrum Karlsruhe Technik und Umwelt |t Wissenschaftliche Berichte |v 6806 |w (DE-604)BV010181833 |9 6806 | |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010251032&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 943 | 1 | |a oai:aleph.bib-bvb.de:BVB01-010251032 | |
Datensatz im Suchindex
| _version_ | 1807322549567094784 |
|---|---|
| adam_text |
TABLE
OF
CONTENTS
ABSTRACT
.
I
ZUSAMMENFASSUNG
.
ILL
TABLE
OF
CONTENTS
.
V
ABBREVIATIONS
.
VIII
1.
INTRODUCTION
.
1
1.1
VALPROIC
ACID
(VPA).
1
1.1.1
POSSIBLE
MECHANISMS
OF
THERAPEUTIC
EFFECTS
OF
VPA
.
1
1.1.2
TERATOGENICITY
OF
VPA
.
2
1.2
PEROXISOME
PROLIFERATOR-ACTIVATED
RECEPTOR
5
(PPAR§)
.
5
1.2.1
THE
FAMILY
OF
PPARS
.
5
1.2.2
EVIDENCE
OF
THE
INVOLVEMENT
OF
PPARS
IN
VPA-INDUCED
TERATOGENICITY
.
5
1.2.3
STRUCTURE
AND
FUNCTIONAL
DOMAINS
OF
PPARS
.
6
1.2.4
THE
EXPRESSION
PATTERN
AND
LIGANDS
OF
PPARS.
9
1.2.5
BIOLOGICAL
FUNCTIONS
OF
PPARS
.
9
1.3
HISTONE
DEACETYLASES
(HDACS)
AND
HDAC
INHIBITORS
.
12
1.3.1
HISTONE
ACETYLATION
AND
TRANSCRIPTIONAL
REGULATION
.
12
1.3.2
THE
FAMILY
OF
HDACS
.
14
1.3.3
BIOLOGICAL
FUNCTIONS
OF
HDACS
.
15
1.3.4
INVOLVEMENT
OF
HDACS
IN
TUMORIGENESIS
.
16
1.3.5
HDAC
INHIBITORS
.
18
1.3.6
REGULATION
OF
HDAC
EXPRESSION
.
22
1.4
THE
UBIQUITIN/PROTEASOME
SYSTEM
.
23
1.5
AIMS
OF
THIS
STUDY
.
25
2.
MATERIALS
AND
METHODS
.
26
2.1
MATERIALS
.
26
2.1.1
CHEMICALS
.
26
2.1.2
OLIGONUCLEOTIDES
.
26
2.1.3
DNA
PROBES
FOR
SOUTHERN
AND
NORTHERN
BLOT
ANALYSIS
.
27
2.1.4
PLASMIDS
.
27
2.1.5
ENZYMES
.
28
2.1.6
ANTIBODIES
.
28
2.1.7
CELL
LINES
.
29
2.2
GENERAL
METHODS
.
31
2.2.1
PREPARATION
OF
CHEMICALLY
COMPETENT
E.
COLL
.
31
2.2.2
TRANSFORMATION
OF
E.
COLI
.
31
2.2.3
SMALL
SCALE
PLASMID
PREPARATION
FROM
BACTERIA
(MINI-PREP)
.
32
2.2.4
LARGE
SCALE
PLASMID
PREPARATION
FROM
BACTERIA
(MAXI-PREP)
.
32
2.2.5
ISOLATION
AND
PURIFICATION
OF
DNA
FROM
AGAROSE
GEL
.
33
2.2.6
RESTRICTION
ENDONUCLEASE
DIGESTION
OF
DNA
.
33
2.2.7
DNA
LIGATION
.
33
2.2.8
SUB-CLONING
.
33
2.2.9
PHENOL/CHLOROFORM
EXTRACTION
OF
NUCLEIC
ACIDS
.
33
2.2.10
DETERMINATION
OF
NUCLEIC
ACID
CONCENTRATION
.
34
2.2.11
ISOLATION
OF
GENOMIC
DNA
FROM
MAMMALIAN
CELLS
.
34
2.2.12
ISOLATION
OF
POLY(A)+
RNA
FROM
MAMMALIAN
CELLS
.
34
2.2.13
POLYMERASE
CHAIN
REACTION
(PCR)
.
35
2.2.14
CELL
CULTURE
.
35
2.2.15
STABLE
AND
TRANSIENT
TRANSFECTION
OF
MAMMALIAN
CEILS
.
37
2.2.16
CELL
EXTRACTS
PREPARATION
.
38
2.2.17
DETERMINATION
OF
PROTEIN
CONCENTRATION
.
39
2.2.18
SDS-POLYACRYLAMIDE
GEL
ELECTROPHORESIS
(SDS-PAGE)
.
40
2.2.19
COOMASSIE
STAINING
.
40
2.2.20
RADIOACTIVE
LABELING
OF
DNA
PROBES
.
40
2.2.21
SOUTHERN
BLOT
ANALYSIS
.
40
2.2.22
NORTHERN
BLOT
ANALYSIS
.
41
2.2.23
STRIPPING
DNA
PROBES
.
41
2.2.24
WESTERN
BLOT
ANALYSIS
.
42
2.2.25
STRIPPING
WESTERN
BLOT
MEMBRANE
.
42
2.2.26
IMMUNOPRECIPITATION
.
43
2.3
ANALYTICAL
METHODS
.
43
2.3.1
PULSE-LABELING
AND
PULSE-CHASE
EXPERIMENT
.
43
2.3.2
IN
VIVO
UBIQUITINATION
ASSAY
.
44
2.3.3
HOECHST
DNA
STAINING
.
45
2.3.4
FLOW
CYTOMETRY
(FACS)
.
45
2.3.5
APOPTOSIS
ASSAY
.
46
2.3.6
IMMUNOHISTOCHEMISTRY
(IHC)
.
46
2.3.7
IN
VITRO
HISTONE
DEACETYLASE
ACTIVITY
ASSAY
(HDAC
ASSAY)
.
47
2.3.8
IN
VITRO
HISTONE
ACETYLTRANSFERASE
ACTIVITY
ASSAY
(HAT
ASSAY)
.
48
2.3.9
IN
VITRO
ALKALINE
PHOSPHATASE
ACTIVITY
ASSAY
(ALP
ASSAY)
.
48
3.
RESULTS
.
49
3.1
EVIDENCE
THAT
HDAC2
IS
REGULATED
BY
PPAR8
.
49
3.1.1
REDUCTION
OF
HDAC
ACTIVITY
IN
PPAR6-DEFICIENT
F9
CELLS
.
50
3.1.2
SELECTIVE
REDUCTION
OF
HDAC2
EXPRESSION
IN
PPARS-DEFICIENT
F9
CELLS
.
51
3.1.3
SELECTIVE
DOWN-REGULATION
OF
HDAC2
IN
PPAR8+/
ES
CELLS
.
53
3.1.4
INDUCTION
OF
HDAC2
UPON
PPAR5
OVEREXPRESSION
.
56
3.1.5
UNCHANGED
HDAC2
EXPRESSION
UPON
LIGAND-ACTIVATION
OF
PPAR8
.
56
3.1.6
SUMMARY
OF
THIS
SECTION
.
57
3.2
ROLES
OF
HDAC2
IN
TRANSFORMED
PHENOTYPE
OF
COLORECTAL
CANCER
CELLS
_
59
3.2.1
REDUCED
HDAC2
EXPRESSION
UPON
RESTORING
WT
APC
IN
HT-29
CELLS
.
61
3.2.2
ELEVATED
HDAC2
EXPRESSION
IN
COLORECTAL
CARCINOMA
TISSUES
.
64
3.2.3
SPECIFIC
KNOCK-DOWN
OF
HDAC2
BY
RNAI
TECHNOLOGY
IN
HT-29
CELL
LINE
.
69
3.2.4
REDUCTION
OF
HDAC2
LEADS
TO
DECREASED
CELL
NUMBERS
IN
HT-29
CELL
CULTURES
.72
3.2.5
REDUCTION
OF
HDAC2
DOES
NOT
AFFECT
THE
CELL
CYCLE
PROGRESSION
OF
HT-29
CELLS.
74
3.2.6
REDUCTION
OF
HDAC2
INCREASES
APOPTOSIS
IN
HT-29
CELLS
.
76
3.2.7
HDAC2
REDUCTION
HAS
A
MODERATE
EFFECT
ON
HT-29
CELL
DIFFERENTIATION
.
79
3.2.8
ECTOPIC
HDAC2
EXPRESSION
ANTAGONIZES
THE
APC-INDUCED
APOPTOSIS
.
81
3.2.9
SUMMARY
OF
THIS
SECTION
.
81
3.3
VPA
SELECTIVELY
INHIBITS
A
SUBSET
OF
HDAC
ACTIVITY
_
_
84
3.3.1
VPA
INHIBITS
N-COR-ASSOCIATED
HDAC
ACTIVITY
IN
VITRO
.
84
3.3.2
VPA
INHIBITS
HDAC2
ACTIVITY
IN
VITRO
.
86
3.3.3
A
VPA-INSENSITIVE
HDAC
SUBSET
IS
ABUNDANT
IN
F9
CELLS
.
86
3.3.4
VPA
PREFERENTIALLY
INHIBITS
CLASS
I
HDACS
.
89
3.3.5
SUMMARY
OF
THIS
SECTION
.
91
3.4
VPA
SELECTIVELY
ACCELERATES
UBIQUITIN/PROTEASOME-MEDIATED
HDAC2
DEGRADATION
.92
3.4.1
VPA,
BUT
NOT
TSA,
SELECTIVELY
REDUCES
HDAC2
PROTEIN
LEVELS
.
92
3.4.2
VPA
DOES
NOT
REDUCE
THE
MRNA
LEVEL
OF
HDAC2
.
94
3.4.3
VPA
ACCELERATES
HDAC2
PROTEIN
DEGRADATION
.
96
3.4.4
VPA
ELEVATES
THE
UBIQUITINATION
OF
HDAC2
PROTEIN
.
99
3.4.5
SUMMARY
OF
THIS
SECTION
.
99
4.
DISCUSSION.
101
4.1
VPA
SELECTIVELY
TARGETS
CLASS
I
HDAC,
IN
PARTICULAR
HDAC2
.
101
4.1.1
VPA
SELECTIVELY
INHIBITS
CLASS
I
HDAC
ACTIVITIES
.
101
4.1.2
VPA
SELECTIVELY
REDUCES
HDAC2
PROTEIN
LEVEL
.
101
4.1.3
MECHANISMS
OF
VPA-INDUCED
HDAC2
DOWN-REGULATION
.
102
4.1.4
ANTI-CANCER
EFFECT
OF
VPA
.
103
4.1.5
CORRELATION
OF
HDAC
INHIBITION
AND
TERATOGENIC
ACTIVITY
OF
VPA-RELATED
COMPOUNDS
.
104
4.2
ROLE
OF
HDAC2
IN
COLORECTAL
CANCER.
104
4.2.1
ABERRANT
HDAC2
EXPRESSION
IS
ESSENTIAL
FOR
THE
TRANSFORMED
PHENOTYPE
OF
HT
29
CELLS
.
104
4.2.2
QUESTIONS
TO
BE
ANSWERED:
IN
VIVO
ROLE,
GENERAL
ONCOGENIC
ROLE
OF
HDAC2
AND
HDAC2-REGULATED
MOLECULE(S)?
.
106
4.2.3
PERSPECTIVES
OF
CLINICAL
RELEVANCE
OF
HDAC2
.
107
4.3
PPAR5
.
107
4.3.1
PPAR8
COULD
BE
A
REGULATOR
OF
HDAC2
EXPRESSION
.
107
4.3.2
MECHANISM
OF
VPA-INDUCED
ACTIVATION
OF
PPARS-DEPENDENT
TRANSCRIPTION
.
108
4.4
SUMMARY
OF
THE
ENTIRE
PROJECT
.
110
5.
REFERENCES
.
111
VII |
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| genre | (DE-588)4113937-9 Hochschulschrift gnd-content |
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| id | DE-604.BV016975273 |
| illustrated | Illustrated |
| indexdate | 2024-08-14T00:58:16Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-010251032 |
| oclc_num | 76726870 |
| open_access_boolean | |
| owner | DE-12 DE-91 DE-BY-TUM |
| owner_facet | DE-12 DE-91 DE-BY-TUM |
| physical | XI, 127 S. Ill., graph. Darst. : 30 cm |
| publishDate | 2002 |
| publishDateSearch | 2002 |
| publishDateSort | 2002 |
| publisher | FZKA |
| record_format | marc |
| series2 | Wissenschaftliche Berichte / Forschungszentrum Karlsruhe Technik und Umwelt |
| spelling | Zhu, Ping Verfasser aut Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells Ping Zhu. Forschungszentrum Karlsruhe GmbH, Karlsruhe Valproic acid and peroxisome proliferator-activated receptor delta are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells Als Ms. gedr. Karlsruhe FZKA 2002 XI, 127 S. Ill., graph. Darst. : 30 cm txt rdacontent n rdamedia nc rdacarrier Wissenschaftliche Berichte / Forschungszentrum Karlsruhe Technik und Umwelt 6806 Zugl.: Karlsruhe, Univ., Diss., 2002 (DE-588)4113937-9 Hochschulschrift gnd-content Forschungszentrum Karlsruhe Technik und Umwelt Wissenschaftliche Berichte 6806 (DE-604)BV010181833 6806 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010251032&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Zhu, Ping Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| subject_GND | (DE-588)4113937-9 |
| title | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| title_alt | Valproic acid and peroxisome proliferator-activated receptor delta are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| title_auth | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| title_exact_search | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| title_full | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells Ping Zhu. Forschungszentrum Karlsruhe GmbH, Karlsruhe |
| title_fullStr | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells Ping Zhu. Forschungszentrum Karlsruhe GmbH, Karlsruhe |
| title_full_unstemmed | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells Ping Zhu. Forschungszentrum Karlsruhe GmbH, Karlsruhe |
| title_short | Valproic acid and peroxisome proliferator-activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| title_sort | valproic acid and peroxisome proliferator activated receptor d are selective modulators of a histone deacetylase with implication for the transformed phenotype of colorectal cancer cells |
| topic_facet | Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=010251032&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| volume_link | (DE-604)BV010181833 |
| work_keys_str_mv | AT zhuping valproicacidandperoxisomeproliferatoractivatedreceptordareselectivemodulatorsofahistonedeacetylasewithimplicationforthetransformedphenotypeofcolorectalcancercells AT zhuping valproicacidandperoxisomeproliferatoractivatedreceptordeltaareselectivemodulatorsofahistonedeacetylasewithimplicationforthetransformedphenotypeofcolorectalcancercells |