RGD Reference Report - ENDOTOXIN ATTENUATES GROWTH HORMONE INDUCED HEPATIC INSULIN-LIKE GROWTH FACTOR-1 EXPRESSION BY INHIBITING JAK2/STAT5 SIGNAL TRANSDUCTION AND STAT5b DNA BINDING.

General

ENDOTOXIN ATTENUATES GROWTH HORMONE INDUCED HEPATIC INSULIN-LIKE GROWTH FACTOR-1 EXPRESSION BY INHIBITING JAK2/STAT5 SIGNAL TRANSDUCTION AND STAT5b DNA BINDING.
Authors:	Chen, Y Sun, D Krishnamurthy, VM Rabkin, R
Citation:	Chen Y, etal., Am J Physiol Endocrinol Metab. 2007 Feb 27;.
RGD ID:	1601383
Pubmed:	PMID:17327369 (View Abstract at PubMed)
DOI:	DOI:10.1152/ajpendo.00581.2006 (Journal Full-text)
Gram negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced IGF-1 expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, required for GH induced IGF-1 expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied four hours later. In liver of these animals, GH induced JAK2 and STAT5 phosphorylation was impaired and appeared to be caused, at least in part, by a marked increase in hepatic TNFα and IL-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine inducible suppressors of cytokine signaling -1, -3 and CIS. Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values, and represents a potential cause of the reduced GH induced IGF-1 expression. In addition, binding of the activated STAT5b to DNA was reduced to an even greater extent and averaged 17% of the normal control value. This provides a further explanation for the impaired IGF-1 gene transcription. Interestingly when endotoxin treated rats were treated with GH, there was a marked increase in pro-inflammatory cytokine gene expression in the liver and if such a response were to occur in humans, this might provide a partial explanation for the adverse effect of GH treatment reported in critically ill patients Key words: lipopolysaccharide, cytokines, inflammation.

RGD Manual Disease Annotations Click to see Annotation Detail View

Only show annotations with direct experimental evidence (0 objects hidden)

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Endotoxemia		ISO	Stat5b (Rattus norvegicus)	1601383; 1601383	protein:decreased tyrosine phosphorylation:liver	RGD
Endotoxemia		IDA		1601383	protein:decreased tyrosine phosphorylation:liver	RGD

Gene Ontology Annotations Click to see Annotation Detail View

Biological Process

Only show annotations with direct experimental evidence (0 objects hidden)

Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
response to lipopolysaccharide		IDA		1601383		RGD

Objects Annotated

Genes (Rattus norvegicus)

Stat5b (signal transducer and activator of transcription 5B)

Genes (Mus musculus)

Stat5b (signal transducer and activator of transcription 5B)

Genes (Homo sapiens)

STAT5B (signal transducer and activator of transcription 5B)

Additional Information

Gene Annotator (Functional Annotation) unavailable	Gene Annotator (Annotation Distribution) unavailable	Variant Visualizer (Genomic Variants) unavailble Variant Visualizer (Genomic Variants) unavailable
Gene Annotator (Functional Annotation)	Gene Annotator (Annotation Distribution)	Variant Visualizer (Genomic Variants)

InterViewer (Protein-Protein Interactions) unavailable	Gviewer (Genome Viewer) unavailable	Variant Visualizer (Damaging Variants) unavailble Variant Visualizer (Damaging Variants) unavailable
InterViewer (Protein-Protein Interactions)	GViewer (Genome Viewer)	Variant Visualizer (Damaging Variants)

Gene Annotator (Annotation Comparison) unavailable	OLGA (Gene List Generator) unavailable
Gene Annotator (Annotation Comparison)	OLGA (Gene List Generator)	Excel (Download)

MOET (Multi-Ontology Enrichement) unavailable	GOLF (Gene-Ortholog Location Finder) unavailable
MOET (Multi-Ontology Enrichement)	GOLF (Gene-Ortholog Location Finder)

Create Name:

Description:

Send us a Message

ENDOTOXIN ATTENUATES GROWTH HORMONE INDUCED HEPATIC INSULIN-LIKE GROWTH FACTOR-1 EXPRESSION BY INHIBITING JAK2/STAT5 SIGNAL TRANSDUCTION AND STAT5b DNA BINDING.