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 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.
Singh
Om V
OV
Department of Pediatrics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21209, USA.
Vij
Neeraj
N
Mogayzel
Peter J
PJ
Jozwik
Cathy
C
Pollard
Harvey B
HB
Zeitlin
Pamela L
PL
D001980:Bronchi / Q000187:drug effects; D002461:Cell Line, Transformed; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000235:genetics; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009154:Mutation; D010654:Phenylbutyrates / Q000494:pharmacology*; D020543:Proteome / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D020545:Respiratory Mucosa / Q000187:drug effects
C505032:CFTR protein, human; D010654:Phenylbutyrates; D020543:Proteome; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C075773:4-phenylbutyric acid