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Titolo:
Endothelin-1 pathway in human alveolar epithelial cell line A549 and humanumbilical vein endothelial cells
Autore:
Deprez-Roy, I; Coge, F; Bertry, L; Galizzi, JP; Feletou, M; Vanhoutte, PM; Canet, E;
Indirizzi:
Inst Rech Servier, Dept Diabetol, F-92150 Suresnes, France Inst Rech Servier Suresnes France F-92150 etol, F-92150 Suresnes, France
Titolo Testata:
ACTA PHARMACOLOGICA SINICA
fascicolo: 6, volume: 21, anno: 2000,
pagine: 499 - 506
SICI:
0253-9756(200006)21:6<499:EPIHAE>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONVERTING ENZYME ECE-1; MOLECULAR CHARACTERIZATION; VASOCONSTRICTOR PEPTIDE; SEQUENCE-ANALYSIS; BIG ENDOTHELIN-1; CLONING; EXPRESSION; GENE; CDNA; ISOFORMS;
Keywords:
endothelin-1; secretion; endothelin receptors;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Feletou, M Inst Rech Servier, Dept Diabetol, 11 Rue Moulineaux, F-92150 Suresnes, France Inst Rech Servier 11 Rue Moulineaux Suresnes France F-92150ce
Citazione:
I. Deprez-Roy et al., "Endothelin-1 pathway in human alveolar epithelial cell line A549 and humanumbilical vein endothelial cells", ACT PHAR SI, 21(6), 2000, pp. 499-506

Abstract

AIM: This study was designed to characterize the endothelin pathway in an immortalized human adenocarcinoma-derived alveolar epithelial cell line (A549) and human umbilical vein endothelial cell line (HUVEC). METHODS: The release of ET-1 and big-ET-1 was measured in the incubation medium of both cell lines. The expression of mRNAs coding for the endothelin isoforms (hppET-1, -2, -3), the endothelin converting enzymes (hECE-1a, b, c, and d) and the hET(A) and hET(B) receptors was investigated using RT-PCR. The expression of ECE-1 mRNA in various human tissues and in A549 cells was investigatedby Northern blot analysis and the subcellular localization of ECE-1 in A549 cells was investigated by immunoblotting using a polyclonal antibody. RESULTS: Under control conditions, HUVEC release both ET-1 and big-ET-1 (ratio5 to 1) while in A549 cells the big-ET-1 levels were below the threshold of detection. The release of these two peptides was minimally affected by various inhibitors of peptidases. However, in both cell lines phosphoramidon produced a concentration-dependent inhibition of ET-1 release and an enhanced accumulation of big-ET-1. Both HUVEC and A549 cells express the mRNAs for ppET-1, ET-A, and ET-B receptor subtypes and ECE-1 (isoforms ECE-1b, c and/or d). In addition, in HUVEC the mRNAs for ppET-2 and for the isoform ECE-1a were also detected. In A549 cells, ECE-1 had a preferential subcellularlocalization in the membrane fraction but was not detected in the cytosol. CONCLUSION: Both A549 and HUVEC produce and release endothelin-1 through aspecific enzymatic pathway, whether or not ECE-1 is the only enzyme involved remains to be determined. A549 might be used as a screening assay for drug discovery such as for inhibitors of endothelin-l release.

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Documento generato il 07/04/20 alle ore 22:58:03