Disease relevance of ECE1

• Regional distribution of endothelin-1 and endothelin converting enzyme-1 in porcine endotoxemia [1].
• Blockade of endothelin-converting enzyme reduces pulmonary hypertension after cardiopulmonary bypass and circulatory arrest [2].

High impact information on ECE1

• The phosphoramidon and thiorphan-dependent increase is not due to direct inhibition of endothelin-converting enzyme not endopeptidase-24.11 but, rather, to an inhibition of the selective turnover of endothelin-converting enzyme protein [3].
• Immunomagnetic separation technology and immunohistochemistry have been used to demonstrate the co-localisation of endothelin-converting enzyme with the established ectoenzyme, aminopeptidase N, on the surface of endothelial cells [3].
• Endothelin-converting enzyme is a phosphoramidon-sensitive membrane metallopeptidase that catalyses the final step in biosynthesis of the potent vasoactive endothelin peptides [3].
• Unlike aminopeptidase N, however, endothelin-converting enzyme is seen to associate in clusters on the plasma membrane which can be distinguished from caveolae both biochemically and immunologically [3].
• Metallopeptidase inhibitors induce an up-regulation of endothelin-converting enzyme levels and its redistribution from the plasma membrane to an intracellular compartment [3].

Biological context of ECE1

• Removal of the rhamnose moiety of phosphoramidon (dipeptide 3) reduced the potency for ECE (IC50 = 70 microM), whereas the potencies for NEP (0.003 microM) and ACE (0.20 microM) were increased [4].
• Subsequent screening of the cDNA library constructed from epithelial cells, a complete cDNA of guinea pig ECE and a partial cDNA encoding preproET-1 were newly isolated [5].

Anatomical context of ECE1

• Pre-treatment of endothelial cells with the metallopeptidase inhibitors phosphoramidon or thiorphan in the range 0.01-100 microM produced a dose-dependent increase in the levels of endothelin-converting enzyme protein and its accumulation in an intracellular compartment [3].
• Expression and function of endothelins, endothelin receptors, and endothelin converting enzyme in the porcine trachea [6].
• In isolated LV myocyte preparations, ECE-1 activity was increased by twofold with CHF (P < 0.05) [7].
• Effects of metalloprotease inhibitors on smooth muscle endothelin-converting enzyme activity [8].
• Endotoxemia is associated with a marked increase in plasma ET-1 and an increase in ppET-1 and ECE-1 mRNA in multiple tissues; however, there was no significant change in tissue ET-1 except in the pulmonary artery [1].

Associations of ECE1 with chemical compounds

• Class-specific inhibitors of serine, cysteine, and aspartic proteases showed no significant effect on ECE activity in L-GPLGM [9].
• ECE activity of L-GPLGM was fully inhibited by phosphoramidon, 1,10-phenanthroline, and EDTA [9].
• A membrane-bound endothelin converting enzyme (ECE) of porcine aortic endothelial cells (ECs) was solubilized with Lubrol PX with high efficiency and stability [10].
• Metalloendoprotease inhibitors (phosphoramidon and DL-thiorphan), but not captopril, inhibited the contractions elicited by human big ET-1 and big ET-2 but DL-thiorphan was less active, suggesting that a non-selective enzymatic process is involved in conversion of big ET-1 and big ET-2 in addition to a phosphoramidon-sensitive ECE [11].
• Phosphoramidon-sensitive ECE activity was not enriched on immunomagnetically separated angiotensin-converting enzyme (ACE)-bearing luminal endothelial membranes from pig lung, whereas ACE showed a sevenfold enrichment [12].

Other interactions of ECE1

• Cathepsin D, a candidate for endothelin-converting enzyme (ECE), was allowed to act on porcine big endothelin-1 (big ET-1, 1-39) [13].
• Effects of dual endothelin-converting enzyme/neutral endopeptidase inhibitors, CGS 26303 and CGS 26393, on lipopolysaccharide or interleukin-1 beta-stimulated release of endothelin from guinea pig tracheal epithelial cells [14].

Analytical, diagnostic and therapeutic context of ECE1

• We investigated possible involvement of these two factors by assessing the effects of (a) phosphoramidon-an inhibitor of endothelin converting enzyme, and (b) vapiprost (GR32191B)-a specific thromboxane A2-receptor antagonist, on the recovery of cerebral blood flow and cerebral oxygen metabolism following deep hypothermic circulatory arrest [15].
• Using a monoclonal antibody to rat lung ECE (AEC32-326) and immunofluorescence microscopy, we have demonstrated ECE on the cell surface of endothelial cell lines [12].
• We used a variety of biochemical and immunologic techniques to investigate the localization of endothelin-converting enzyme (ECE) in porcine lung, in human umbilical vein endothelial cells (HUVECs), and in the transformed endothelial cell line EA.hy926 [12].
• VEGF and steroid levels in luteal tissue were determined by ELISA and RIA, respectively; VEGF, VEGFR-2, ET-1, ET-A and ECE-1 mRNAs expression was measured by real-time PCR [16].
• Northern blot analysis revealed that mRNA level of ET-1 was increased in the LPS stimulated epithelial cells, but the effect on the ECE mRNA expression was obscure [5].

References