P-glycoprotein expression increases ATP release in respiratory cystic fibrosis cells.
P-glycoprotein (Pgp) is a well-defined ATP-binding cassette (ABC) protein and a close relative of cystic fibrosis transmembrane conductance regulator (CFTR), whose dysfunction causes cystic fibrosis (CF). It is postulated that Pgp can complement deficient CFTR functions because of structural and functional homologies. One of the most relevant functions appears to be the regulation of ATP release, which influences mucociliary clearance in respiratory epithelia by nucleotide receptor stimulation. However, mechanisms involved in ATP secretion remain a controversial issue. In the present study, CF epithelial cells (sigmaCFTE29ó) were transduced with the retroviral vector MP1m encoding Pgp, and thus, a stable Pgp-overexpressing CF cell line (sigmaCFTE29óPgp) was established and used for studies of hypothesized CFTR complementation. In addition, overexpression of native Pgp in sigmaCFTE29ó could also be achieved by long-term treatment with colchicine, a drug, which may be of great interest in CF therapy. We confirmed that overexpression of Pgp causes a significant increase in cellular ATP release, which could even be enhanced by stimulation with hypoosmolar medium. A potential clinical benefit is discussed.
Naumann
Nora
N
Department of Pediatrics, University Clinic Carl Gustav Carus, Dresden, Germany.
Siratska
Olga
O
Gahr
Manfred
M
Rösen-Wolff
Angela
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014132:Trachea / Q000473:pathology; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000255:Adenosine Triphosphate; D003078:Colchicine