title: Characterization of endothelin converting enzyme from intact cells of a permanent human endothelial cell line, EA.hy926.
abstract: Endothelin converting enzyme (ECE) from intact cells of a permanent human endothelial cell line, EA.hy926, was studied by examining the effects of phosphoramidon, an endothelin converting enzyme inhibitor, on the levels of secreted endothelin-1 and big endothelin-1. The specific ECE activity was demonstrated by a phosphoramidon dose-dependent decrease in ET-1 level with a concomitant increase in big ET-1 level. By using a specific neutral endopeptidase 24.11 (NEP 24.11) inhibitor, thiorphan, it was also shown that the phosphoramidon-sensitive ET-1 degrading activity in this cell line is due to the NEP 24.11 activity. Other serine, acid, and cysteine protease inhibitors had no effect on the endogenous synthesis of ET-1 and big ET-1 supporting the evidence that ECE is insensitive to these protease inhibitors as has been demonstrated with the isolated enzyme.
authors.affiliation: Department of Biochemistry, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ahn
authors.forename: S M
authors.initials: SM
authors.lastname: Pan
authors.forename: M A
authors.initials: MA
authors.lastname: Zientek
authors.forename: P M
authors.initials: PM
authors.lastname: Guy
authors.forename: A M
authors.initials: AM
authors.lastname: Sisneros
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D004717:Endometrium / Q000187:drug effects / Q000201:enzymology; D019332:Endothelin-1 / Q000096:biosynthesis / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000096:biosynthesis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases; D011498:Protein Precursors / Q000096:biosynthesis / Q000378:metabolism*; D011863:Radioimmunoassay; D015244:Thiorphan / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D011498:Protein Precursors; D015244:Thiorphan; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes; C008890:phosphoramidon