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Article: Endothelin-1 pathway in human alveolar epithelial cell line A549 and human umbilical vein endothelial cells
Title | Endothelin-1 pathway in human alveolar epithelial cell line A549 and human umbilical vein endothelial cells |
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Authors | |
Keywords | Endothelin receptors Endothelin-1 Secretion |
Issue Date | 2000 |
Citation | Acta Pharmacologica Sinica, 2000, v. 21 n. 6, p. 499-506 How to Cite? |
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-la, 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 investigated by 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 (ratio 5 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 subcellular localization in the membrane fraction but was not detected in the cytosol. CONCLUSION: Both A549 and HUVEC produce and release endothelin-1 through a specific 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-1 release. |
Persistent Identifier | http://hdl.handle.net/10722/171241 |
ISSN | |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | DeprezRoy, I | en_US |
dc.contributor.author | Coge, F | en_US |
dc.contributor.author | Bertry, L | en_US |
dc.contributor.author | Galizzi, JP | en_US |
dc.contributor.author | Feletou, M | en_US |
dc.contributor.author | Vanhoutte, PM | en_US |
dc.contributor.author | Canet, E | en_US |
dc.date.accessioned | 2012-10-30T06:12:54Z | - |
dc.date.available | 2012-10-30T06:12:54Z | - |
dc.date.issued | 2000 | en_US |
dc.identifier.citation | Acta Pharmacologica Sinica, 2000, v. 21 n. 6, p. 499-506 | en_US |
dc.identifier.issn | 0253-9756 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/171241 | - |
dc.description.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-la, 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 investigated by 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 (ratio 5 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 subcellular localization in the membrane fraction but was not detected in the cytosol. CONCLUSION: Both A549 and HUVEC produce and release endothelin-1 through a specific 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-1 release. | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Acta Pharmacologica Sinica | en_US |
dc.subject | Endothelin receptors | - |
dc.subject | Endothelin-1 | - |
dc.subject | Secretion | - |
dc.subject.mesh | Adenocarcinoma - Pathology | en_US |
dc.subject.mesh | Aspartic Acid Endopeptidases - Biosynthesis - Genetics | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Endothelin-1 - Secretion | en_US |
dc.subject.mesh | Endothelins - Biosynthesis - Genetics | en_US |
dc.subject.mesh | Endothelium, Vascular - Cytology - Metabolism | en_US |
dc.subject.mesh | Glycopeptides - Pharmacology | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Lung Neoplasms - Pathology | en_US |
dc.subject.mesh | Metalloendopeptidases | en_US |
dc.subject.mesh | Protein Precursors - Biosynthesis - Genetics | en_US |
dc.subject.mesh | Rna, Messenger - Biosynthesis | en_US |
dc.subject.mesh | Tumor Cells, Cultured | en_US |
dc.subject.mesh | Umbilical Veins - Cytology - Metabolism | en_US |
dc.title | Endothelin-1 pathway in human alveolar epithelial cell line A549 and human umbilical vein endothelial cells | en_US |
dc.type | Article | en_US |
dc.identifier.email | Vanhoutte, PM:vanhoutt@hku.hk | en_US |
dc.identifier.authority | Vanhoutte, PM=rp00238 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.pmid | 11360683 | - |
dc.identifier.scopus | eid_2-s2.0-0034045779 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0034045779&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 21 | en_US |
dc.identifier.issue | 6 | en_US |
dc.identifier.spage | 499 | en_US |
dc.identifier.epage | 506 | en_US |
dc.identifier.isi | WOS:000087561300003 | - |
dc.identifier.scopusauthorid | DeprezRoy, I=6504471806 | en_US |
dc.identifier.scopusauthorid | Coge, F=6602987151 | en_US |
dc.identifier.scopusauthorid | Bertry, L=6504401404 | en_US |
dc.identifier.scopusauthorid | Galizzi, JP=7004145226 | en_US |
dc.identifier.scopusauthorid | Feletou, M=7006461826 | en_US |
dc.identifier.scopusauthorid | Vanhoutte, PM=7202304247 | en_US |
dc.identifier.scopusauthorid | Canet, E=7006072145 | en_US |
dc.identifier.issnl | 0253-9756 | - |