Disease relevance of Ece1

• Mutations in ECE-1 may cause developmental defects in humans, such as Hirschsprung disease, velocardiofacial syndrome and related neurocristopathies [1].
• Impaired ventilatory responses to hypoxia in mice deficient in endothelin-converting-enzyme-1 [2].
• Baseline breathing variables and ventilatory responses to hypercapnia were normal in the ECE-1+/- newborn mice [2].
• These findings suggest that although ECE inhibition by AM-A was mainly attributable to its chelating activity, it showed apparent in vivo activities due to ECE inhibition with low toxicity [3].
• Prophylactic use of melatonin protects against focal cerebral ischemia in mice: role of endothelin converting enzyme-1 [4].

High impact information on Ece1

• In this study, in situ hybridization of ETA-/- and ECE-1(-)/- embryos with a cardiac neural crest marker, cellular retinoic acid-binding protein-1, shows that the migration of neural crest cells from the neural tube to cardiac outflow tract is not affected in these embryos [5].
• Immunostaining of an endothelial marker, platelet endothelial cell adhesion molecule CD-31, shows that the initial formation of the branchial arch arteries is not disturbed in ETA-/- or ECE-1(-)/- embryos [5].
• Endothelin-converting enzyme catalyses the final step in the biosynthesis of the vasoconstrictor peptide, endothelin (ET) [6].
• Angiotensin-converting enzyme, neprilysin and endothelin-converting enzyme function as vasopeptidases and are the targets of drugs designed to treat cardiovascular disorders, and ACE inhibitors are commonly prescribed [7].
• Interaction of a plasma membrane isoform with ECE-1b resulted in its intracellular localization and decreased its extracellular activity [8].

Biological context of Ece1

• Ece1 and Tbx1 define distinct pathways to aortic arch morphogenesis [9].
• As with the human gene, the exons containing isoform-specific sequences were localised in the 5' terminal region of the murine Ece1 gene [10].
• By comparative sequence analysis using exon-specific sequences of human and rat ECE-1 we have resolved the complete exon-intron structure of the murine Ece1 locus on chromosome 4 [10].
• Endothelium dependent relaxation to acetylcholine and vascular gene expression of endothelin converting enzyme (ECE) isoforms 1 and 2 were studied as indicators of vascular injury [11].
• WS75624 A and B showed highly potent ECE inhibitory activity, and both had IC50 values of 0.03 microgram/ml [12].

Anatomical context of Ece1

• Genetic disruption of this ET-1/ECE-1/ETA pathway results in defects in branchial arch- derived craniofacial tissues, as well as defects in cardiac outflow and great vessel structures, which are derived from cephalic (cardiac) neural crest [5].
• We found that both intracellular isoforms were concentrated in the endosomal system: ECE-1d in recycling endosomes, and ECE-1b in late endosomes/multivesicular bodies [8].
• Evidence for atypical endothelin receptors and for presence of endothelin-converting enzyme activity in the mouse isolated vas deferens [13].
• Role of endothelin-converting enzyme, chymase and neutral endopeptidase in the processing of big ET-1, ET-1(1-21) and ET-1(1-31) in the trachea of allergic mice [14].
• Six different mouse hybridoma cell lines have been generated secreting monoclonal antibodies specific to human ECE-1 [15].

Associations of Ece1 with chemical compounds

• The endothelin-converting enzyme (ECE) inhibitor, phosphoramidon, and endothelin type-A (ETA) receptor antagonist BQ-123 reduced expression of CD44 in VSMC [16].
• Leucine-based motifs were involved in the intracellular retention of these isoforms, and the targeting of ECE-1b to the degradation pathway required an additional signal in the N terminus [8].
• 4. A metalloproteinase inhibitor, phosphoramidon (10 mg kg-1, i.v.), which inhibits the activity of endothelin converting enzyme (ECE), delayed the onset of big ET-1-induced haemoconcentration, but failed to alter the maximal value and the duration of the haemoconcentration [17].
• ECE-1 mRNA was unaltered in the CARV and LOS group and was decreased by 20% in the QIN group [18].
• EDTA also inhibited ECE (IC50 = 1.1 microM), but the inhibitions by AM-A, AM-B and EDTA were each abolished by the addition of 10 microM Zn2+ to the reaction mixture [3].

Regulatory relationships of Ece1

• The ECE inhibitor CGS35066 (10 microM) inhibited contractions induced by big ET-1 (4.8-fold rightward shift of dose-response curve; P<0.05), but not those induced by either ET-1(1-21) or ET-1(1-31) [14].

Other interactions of Ece1

• Interleukin-1beta attenuates endothelin B receptor-mediated airway contractions in a murine in vitro model of asthma: roles of endothelin converting enzyme and mitogen-activated protein kinase pathways [19].
• Endothelin-converting enzyme-like 1 (ECEL1) is a putative zinc metalloprotease that was recently identified on the basis of its strong similarity to endothelin-converting enzyme 1 [20].

Analytical, diagnostic and therapeutic context of Ece1

• ET-1 and ECE mRNA expression was markedly increased by RT-PCR in PbA-infected mice [21].
• Northern blot analysis of preproendothelin-1 (preproET-1) and endothelin-converting enzyme-1 (ECE-1) expression revealed a significant (p < 0.05) 20% decrease in preproET-1 mRNA in the mRen2 rats in the RV and in the LV, compared to SD rats [18].
• To test whether brain protection involved vascular mechanisms, as suggested earlier, the effects of melatonin on endothelin converting enzyme-1 (ECE-1) levels were studied using Western blots [4].

References