Linked Life Data

19845467

Source:http://linkedlifedata.com/resource/pubmed/id/19845467

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-2-22
pubmed:abstractText
Heat shock protein 90 (Hsp90), encoded by the murine hsp84 and hsp86 genes in mice, is a pivotal regulator of glucocorticoid receptor (GR) function in the hypothalamus-pituitary-adrenal axis and affords stress protection. To explore the underlying molecular mechanisms of strain susceptibility to traumatic stress, we investigated the alteration by Hsp90 of the function of the glucocorticoid-glucocorticoid receptor (GC-GR) pathway in attenuating stress responses in C57BL/6 and BALB/c mice using the whole-body blast injury (WBBI) model. We found that C57BL/6 mice had a lower WBBI-induced mortality, higher nuclear GR level, and higher glucocorticoid-response element (GRE) binding activity than BALB/c mice. This study is the first report identifying four genetic variations of the murine hsp84 gene: 226A>C, 996G>C, 1483G>C, and 2000G>T. These nucleotide changes occur in the functional domains associated with the nuclear/cytosolic translocation of GR, GR-Hsp90 interaction, ATP binding, and self-dimerization of Hsp90, respectively. Further, we used a specific Hsp90 inhibitor, geldanamycin (GA), to assess the role of Hsp90 in the discriminative traumatic response in C57BL/6 mice. Pretreatment with GA reduced nuclear GR levels and GRE binding activity, and enhanced WBBI-induced mortality. These findings suggest that Hsp90 may underlie the strain-selective (C57BL/6 versus BALB/c) susceptibility to WBBI by mediating the nuclear translocation of GRs and GRE binding. Thus, pharmacological manipulation of Hsp90 may represent a therapeutic strategy to modify the function of the GC-GR pathway and traumatic stress response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1557-9042
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
373-81
pubmed:meshHeading
pubmed-meshheading:19845467-Animals, pubmed-meshheading:19845467-Benzoquinones, pubmed-meshheading:19845467-Blast Injuries, pubmed-meshheading:19845467-Blotting, Western, pubmed-meshheading:19845467-Enzyme Inhibitors, pubmed-meshheading:19845467-Genetic Predisposition to Disease, pubmed-meshheading:19845467-HSP90 Heat-Shock Proteins, pubmed-meshheading:19845467-Hypothalamo-Hypophyseal System, pubmed-meshheading:19845467-Lactams, Macrocyclic, pubmed-meshheading:19845467-Male, pubmed-meshheading:19845467-Mice, pubmed-meshheading:19845467-Mice, Inbred BALB C, pubmed-meshheading:19845467-Mice, Inbred C57BL, pubmed-meshheading:19845467-Pituitary-Adrenal System, pubmed-meshheading:19845467-Polymorphism, Single Nucleotide, pubmed-meshheading:19845467-Receptors, Glucocorticoid, pubmed-meshheading:19845467-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:19845467-Stress, Physiological, pubmed-meshheading:19845467-Wounds and Injuries
pubmed:year
2010
pubmed:articleTitle
Differential alteration of heat shock protein 90 in mice modifies glucocorticoid receptor function and susceptibility to trauma.
pubmed:affiliation
Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't