CFTR gene transfer corrects defective glycoconjugate secretion in human CF epithelial tracheal cells
| Autor: | Mustapha Lemnaouar, A. Paul, Jean-Yves Picard, M.-C. Brahimi-Horn, D. C. Gruenert, D. Veissiere, M. Perricaudet, Martine Mergey, Jacqueline Capeau |
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| Rok vydání: | 1995 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty DNA Complementary Cystic Fibrosis Physiology Glycoconjugate Genetic Vectors Molecular Sequence Data Cystic Fibrosis Transmembrane Conductance Regulator Epithelium Adenoviridae Chlorides Physiology (medical) Internal medicine medicine Cyclic AMP Humans Secretion Protein kinase A Protein kinase C Protein Kinase C chemistry.chemical_classification biology Base Sequence Genetic transfer Electric Conductivity Gene Transfer Techniques Cell Biology Cyclic AMP-Dependent Protein Kinases Cystic fibrosis transmembrane conductance regulator Cell biology Trachea Endocrinology chemistry Cell culture Molecular Probes biology.protein Signal transduction Glycoconjugates |
| Zdroj: | The American journal of physiology. 269(6 Pt 1) |
| ISSN: | 0002-9513 |
| Popis: | We demonstrate that in immortalized normal human tracheal epithelial cells (NT-1 and 56FHTE8o-) 14C-labeled glycoconjugate secretion may be regulated independently by agonists of the protein kinase A (PKA) and protein kinase C (PKC) signaling pathways. In contrast, in immortalized cystic fibrosis (CF) human tracheal epithelial cells (CFT-1 and CFT-2), regulation is defective for agonists specific for the PKA but not for the PKC pathway. To characterize the involvement of the cystic fibrosis transmembrane conductance regulator (CFTR) in regulated glycoconjugate secretion, we examined the effect of adenovirus-mediated gene transfer of CFTR to CF and control cells. Forty-eight hours after infection, at a multiplicity of infection of 50 plaque-forming units per cell, high levels of CFTR mRNA were detected by reverse transcription-polymerase chain reaction, and de novo synthesis of CFTR protein was demonstrated by immunoblotting. Gene transfer to CF cells restored defective adenosine 3',5'-cyclic monophosphate (cAMP)-dependent secretion not only of chloride but also of glycoconjugates. Taken together, these results argue for a role for CFTR in cAMP-mediated glycoconjugate secretion. |
| Databáze: | OpenAIRE |
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