Linked Life Data

14583596

Source:http://linkedlifedata.com/resource/pubmed/id/14583596

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-16
pubmed:abstractText
Most individuals with cystic fibrosis (CF) carry one or two mutations that result in a maturation defect of the full-length CFTR protein. The DeltaF508 mutation results in a mutant protein that is degraded by the proteosome instead of progressing to the apical membrane where it functions as a cAMP-regulated chloride channel. 4-Phenylbutyrate (PBA) modulates heat-shock protein expression and promotes trafficking of DeltaF508, thus permitting maturation and membrane insertion. The goal of this study was to gain insight into the genetic mechanism of PBA action through a large-scale analysis of gene expression. The Affymetrix genome-spanning U133 microarray set was used to compare mRNA expression levels in untreated IB3-1 cell line cultures with cultures treated with 1 mM PBA for 12 and 24 h. The most notable changes in mRNA levels were transient elevations in heat-shock proteins. The majority of genes downregulated throughout the application period were functionally associated with control of gene expression. Another set of genes increased in expression starting at 24 h, suggesting these are downstream effects of altered gene expression initiated by PBA. More than one-third of the genes in this late expressing set were identified as having potential significance in understanding the pathology of CF. Our results demonstrate the usefulness of gene expression profile analysis in understanding the consequences of PBA treatment and provide insights in how this drug exerts its effect on the trafficking of CFTR.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1531-2267
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
204-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins.
pubmed:affiliation
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. jwright@jhmi.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't