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40
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Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1074/jbc.M502751200" target="_blank" rel="noreferrer noopener">http://doi.org/10.1074/jbc.M502751200</a>
Pages
30517–30525
Issue
34
Volume
280
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Bcl-2 positively regulates Sox9-dependent chondrocyte gene expression by suppressing the MEK-ERK1/2 signaling pathway.
Publisher
An entity responsible for making the resource available
The Journal of biological chemistry
Date
A point or period of time associated with an event in the lifecycle of the resource
2005
2005-08
Subject
The topic of the resource
*Gene Expression Regulation; Adenoviridae/genetics; Animals; Apoptosis; beta-Galactosidase/metabolism; Blotting; Butadienes/pharmacology; Caspase Inhibitors; Cell Differentiation; Cell Line; Chondrocytes/*metabolism; Collagen Type II/metabolism; Down-Regulation; Enzyme Inhibitors/pharmacology; Fibroblasts/metabolism; Fluorescence; Genetic; High Mobility Group Proteins/*metabolism; Lac Operon; Luciferases/metabolism; MAP Kinase Kinase Kinases/*metabolism; Messenger/metabolism; Microscopy; Mitogen-Activated Protein Kinase 1/*metabolism; Mitogen-Activated Protein Kinase 3/*metabolism; NF-kappa B/metabolism; Nitriles/pharmacology; Phenotype; Phosphorylation; Promoter Regions; Protein Kinase C-alpha; Protein Kinase C/antagonists & inhibitors; Proteoglycans/metabolism; Proto-Oncogene Proteins c-bcl-2/*metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA; Signal Transduction; Small Interfering/metabolism; SOX9 Transcription Factor; Sprague-Dawley; Time Factors; Transcription; Transcription Factors/*metabolism; Transfection; Western
Creator
An entity primarily responsible for making the resource
Yagi Rieko; McBurney Denise; Horton Walter E Jr
Description
An account of the resource
Bcl-2 is an anti-apoptotic protein that has recently been shown to regulate other cellular functions. We previously reported that Bcl-2 regulates chondrocyte matrix gene expression, independent of its anti-apoptotic function. Here, we further investigate this novel function of Bcl-2 and examine three intracellular signaling pathways likely to be associated with this function. The present study demonstrates that the activity of Sox9, a master transcription factor that regulates the gene expression of chondrocyte matrix proteins, is suppressed by Bcl-2 small interference RNA in the presence of caspase inhibitors. This effect was attenuated by prior exposure of chondrocytes to an adenoviral vector expressing sense Bcl-2. In addition, the down-regulation of Bcl-2, Sox9, and chondrocyte-specific gene expression by serum withdrawal in primary chondrocytes was reversed by expressing Bcl-2. Inhibition of the protein kinase C alpha and NFkappaB pathways had no effect on the maintenance of Sox9-dependent gene expression by Bcl-2. In contrast, whereas the MEK-ERK1/2 pathway negatively regulated the differentiated phenotype in wild type chondrocytes, inhibition of this pathway reversed the loss of differentiation markers and fibroblastic phenotype in Bcl-2-deficient chondrocytes. In conclusion, the present study identifies a specific signaling pathway, namely, MEK-ERK1/2, that is downstream of Bcl-2 in the regulation of Sox9-dependent chondrocyte gene expression and phenotype.
Identifier
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<a href="http://doi.org/10.1074/jbc.M502751200" target="_blank" rel="noreferrer noopener">10.1074/jbc.M502751200</a>
Rights
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Gene Expression Regulation
2005
Adenoviridae/genetics
Animals
Apoptosis
beta-Galactosidase/metabolism
Blotting
Butadienes/pharmacology
Caspase Inhibitors
Cell Differentiation
Cell Line
Chondrocytes/*metabolism
Collagen Type II/metabolism
Department of Anatomy & Neurobiology
Down-Regulation
Enzyme Inhibitors/pharmacology
Fibroblasts/metabolism
Fluorescence
Genetic
High Mobility Group Proteins/*metabolism
Horton Walter E Jr
Lac Operon
Luciferases/metabolism
MAP Kinase Kinase Kinases/*metabolism
McBurney Denise
Messenger/metabolism
Microscopy
Mitogen-Activated Protein Kinase 1/*metabolism
Mitogen-Activated Protein Kinase 3/*metabolism
NEOMED College of Medicine
NF-kappa B/metabolism
Nitriles/pharmacology
Phenotype
Phosphorylation
Promoter Regions
Protein Kinase C-alpha
Protein Kinase C/antagonists & inhibitors
Proteoglycans/metabolism
Proto-Oncogene Proteins c-bcl-2/*metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
RNA
Signal Transduction
Small Interfering/metabolism
SOX9 Transcription Factor
Sprague-Dawley
The Journal of biological chemistry
Time Factors
Transcription
Transcription Factors/*metabolism
Transfection
Western
Yagi Rieko
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">http://doi.org/10.1002/hep.22627</a>
Pages
297–305
Issue
1
Volume
49
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression.
Publisher
An entity responsible for making the resource available
Hepatology (Baltimore, Md.)
Date
A point or period of time associated with an event in the lifecycle of the resource
2009
2009-01
Subject
The topic of the resource
Butadienes/pharmacology; Carcinoma; Cell Line; Chenodeoxycholic Acid/*pharmacology; Cholesterol 7-alpha-Hydroxylase/*biosynthesis; Cytoplasmic and Nuclear/metabolism/physiology; DNA-Binding Proteins/metabolism; Fibroblast Growth Factor; Fibroblast Growth Factors/drug effects/*physiology; Gene Expression/drug effects; Hepatocellular/metabolism; Hepatocytes/metabolism; Humans; Isoxazoles/pharmacology; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Nitriles/pharmacology; Receptor; Receptors; Signal Transduction/drug effects; Transcription Factors/metabolism; Tumor; Type 4/antagonists & inhibitors
Creator
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Song Kwang-Hoon; Li Tiangang; Owsley Erika; Strom Stephen; Chiang John Y L
Description
An account of the resource
UNLABELLED: Mouse fibroblast growth factor 15 (FGF15) and human ortholog FGF19 have been identified as the bile acid-induced intestinal factors that mediate bile acid feedback inhibition of cholesterol 7alpha-hydroxylase gene (C YP7A1) transcription in mouse liver. The mechanism underlying FGF15/FGF19 inhibition of bile acid synthesis in hepatocytes remains unclear. Chenodeoxycholic acid (CDCA) and the farnesoid X receptor (FXR)-specific agonist GW4064 strongly induced FGF19 but inhibited CYP7A1 messenger RNA (mRNA) levels in primary human hepatocytes. FGF19 strongly and rapidly repressed CYP7A1 but not small heterodimer partner (SHP) mRNA levels. Kinase inhibition and phosphorylation assays revealed that the mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/Erk1/2) pathway played a major role in mediating FGF19 inhibition of CYP7A1. However, small interfering RNA (siRNA) knockdown of SHP did not affect FGF19 inhibition of CYP7A1. Interestingly, CDCA stimulated tyrosine phosphorylation of the FGF receptor 4 (FGFR4) in hepatocytes. FGF19 antibody and siRNA specific to FGFR4 abrogated GW4064 inhibition of CYP7A1. These results suggest that bile acid-activated FXR is able to induce FGF19 in hepatocytes to inhibit CYP7A1 by an autocrine/paracrine mechanism. CONCLUSION: The hepatic FGF19/FGFR4/Erk1/2 pathway may inhibit CYP7A1 independent of SHP. In addition to inducing FGF19 in the intestine, bile acids in hepatocytes may activate the liver FGF19/FGFR4 signaling pathway to inhibit bile acid synthesis and prevent accumulation of toxic bile acid in human livers.
Identifier
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<a href="http://doi.org/10.1002/hep.22627" target="_blank" rel="noreferrer noopener">10.1002/hep.22627</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2009
Butadienes/pharmacology
Carcinoma
Cell Line
Chenodeoxycholic Acid/*pharmacology
Chiang John Y L
Cholesterol 7-alpha-Hydroxylase/*biosynthesis
Cytoplasmic and Nuclear/metabolism/physiology
Department of Integrative Medical Sciences
DNA-Binding Proteins/metabolism
Fibroblast Growth Factor
Fibroblast Growth Factors/drug effects/*physiology
Gene Expression/drug effects
Hepatocellular/metabolism
Hepatocytes/metabolism
Hepatology (Baltimore, Md.)
Humans
Isoxazoles/pharmacology
Li Tiangang
Mitogen-Activated Protein Kinase 1/metabolism
Mitogen-Activated Protein Kinase 3/metabolism
NEOMED College of Medicine
Nitriles/pharmacology
Owsley Erika
Receptor
Receptors
Signal Transduction/drug effects
Song Kwang-Hoon
Strom Stephen
Transcription Factors/metabolism
Tumor
Type 4/antagonists & inhibitors