Pharmacoproteomics of 4-Phenylbutyrate-Treated IB3-1 Cystic Fibrosis Bronchial Epithelial Cells

4-Phenylbutyrate (4-PBA) is an oral butyrate derivative that has recently been approved for treatment of urea cycle disorders and is under investigation in clinical trials of cancer, hemoglobinopathies, and cystic fibrosis (CF). We hypothesized that proteome profiling of IB3-1 cystic fibrosis bronch...

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Bibliographic Details
Published in:Journal of proteome research 2006-03, Vol.5 (3), p.562-571
Main Authors: Singh, Om V, Vij, Neeraj, Mogayzel, Peter J, Jozwik, Cathy, Pollard, Harvey B, Zeitlin, Pamela L
Format: Article
Language:English
Subjects:
Bronchi - drug effects
Cell Line, Transformed
Cystic Fibrosis - drug therapy
Cystic Fibrosis - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Electrophoresis, Gel, Two-Dimensional
Epithelial Cells - drug effects
Gene Expression Regulation - drug effects
Humans
Mutation
Phenylbutyrates - pharmacology
Proteome - drug effects
Proteome - genetics
Proteome - metabolism
Proteomics
Respiratory Mucosa - drug effects
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Summary:4-Phenylbutyrate (4-PBA) is an oral butyrate derivative that has recently been approved for treatment of urea cycle disorders and is under investigation in clinical trials of cancer, hemoglobinopathies, and cystic fibrosis (CF). We hypothesized that proteome profiling of IB3-1 cystic fibrosis bronchial epithelial cells treated with 4-PBA would identify butyrate-responsive cellular chaperones, protein processing enzymes, and cell trafficking molecules associated with the amelioration of the chloride transport defect in these cells. Protein profiles were analyzed by two-dimensional gel electrophoresis and mass spectrometry. Over a pI range of 4−7 and molecular weight from 20 to 150 kDa a total of 85 differentially expressed proteins were detected. Most of the identified proteins were chaperones, catalytic enzymes, and proteins comprising structural elements, cellular defense, protein biosynthesis, trafficking activity, and ion transport. Subsets of these proteins were confirmed by immunoblot analysis. These data represent a first-draft of the pharmacoproteomics map of 4-PBA treated cystic fibrosis bronchial epithelial cells. Keywords: cystic fibrosis • chaperone • chloride transport • proteasome • two-dimensional gel electrophoresis
ISSN:1535-3893
1535-3907
DOI:10.1021/pr050319o