Characterization of the enzyme involved in the processing of big endothelin-1 in human lung epithelial cells.

Détails

ID Serval
serval:BIB_8251592424A0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Characterization of the enzyme involved in the processing of big endothelin-1 in human lung epithelial cells.
Périodique
Pulmonary pharmacology & therapeutics
Auteur(s)
Aubert J.D., Carnal B., Ricou J., Fioroni P., Juillerat-Jeanneret L., Pinet F.
ISSN
1094-5539
Statut éditorial
Publié
Date de publication
1998
Peer-reviewed
Oui
Volume
11
Numéro
2-3
Pages
209-13
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. - Publication Status: ppublish
Résumé
Biosynthesis of active endothelin-1 (ET-1) implies an enzymatic processing of the inactive precursor Big ET-1 (1-39) into the mature, 21 amino acid peptide. The aim of this study was to characterize in airway and alveolar epithelial cells the enzymes responsible for this activation. BEAS-2B and A549 cells, which both produce ET-1, were studied in vitro as models for bronchiolar and alveolar cells, respectively. Both cell lines were able to convert exogenously added Big ET-1 (0.1 microM) into ET-1, suggesting a cell surface or an extracellular processing. The conversion was inhibited by phosphoramidon in both cell lines with an IC50 approximately 1 microM, but not by thiorphan, a specific inhibitor of neutral endopeptidase 24.11 (NEP). The endogenous production of serum-stimulated BEAS-2B and A549 cells was not inhibited by thiorphan, and phosphoramidon showed inhibition only at high concentration (>100 microM). Western blotting following electrophoresis in reducing conditions demonstrated a protein of MR 110 corresponding to the ECE-1 monomer in both BEAS-2B and A549 cells, as well as in whole lung extracts. By RT-PCR we revealed the mRNA encoding for the ECE-1b and/or -1c subtype, but not ECE-1a, in both cell lines. We conclude that BEAS-2B and A549 cells are able to process either endogenous or exogenous Big ET-1 by ECE-1 and that isoforms 1b and 1c could be involved in this processing with no significant role of NEP.
Mots-clé
Cell Line, Endothelin-1, Endothelins, Epithelial Cells, Glycopeptides, Humans, Lung, Neprilysin, Protease Inhibitors, Protein Isoforms, Protein Precursors, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Thiorphan
Pubmed
Web of science
Création de la notice
21/01/2008 13:54
Dernière modification de la notice
03/03/2018 18:50
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