Disease relevance of ECE1

• Escherichia coli lipopolysaccharide (LPS) was used to stimulate ET-1 synthesis, and brefeldin A, monensin, colchicine or cytochalasin B, which disrupt peptide biosynthetic pathways in a variety of ways, were tested for their ability to modify changes in ET-1 synthesis and ECE levels [1].

High impact information on ECE1

• We report the identification of ECE-1, a novel membrane-bound neutral metalloprotease that is expressed abundantly in endothelial cells in vivo and is structurally related to neutral endopeptidase 24.11 and Kell blood group protein [2].
• ECE-1: a membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1 [2].
• When transfected into cultured cells that normally secrete only big ET-1, the ECE-1 cDNA conferred the ability to secrete mature ET-1 [2].
• Endothelin-converting enzyme-1 (ECE-1) cleaves big endothelins, as well as bradykinin and beta-amyloid peptide [3].
• Several isoforms of ECE-1 (a-d) have been identified to date; they differ only in their NH(2) terminus but share the catalytic domain located in the COOH-terminal end [3].

Biological context of ECE1

• Thus, the spatial and temporal pattern of ECE-1 expression determines the site of big ET-1 activation and the bioavailability of ET-1 [4].
• The predicted amino acid sequence of bovine ECE consisted of 758 amino acid residues [5].
• Distinct cellular localization and regulation of endothelin-1 and endothelin-converting enzyme-1 expression in the bovine corpus luteum: implications for luteolysis [6].
• Low ECE-1 levels during the early luteal phase, restricting the production of active ET-1, may explain why the immature CL is able to withstand PGF(2 alpha)-induced luteolysis [6].
• In addition, these data demonstrate that phosphoramidon, which presumably inhibits the endothelin converting enzyme, can inhibit ET release over a range of cell densities without affecting cell viability [7].

Anatomical context of ECE1

• Using enriched follicular and luteal cell subpopulations and in situ hybridization techniques, we showed that the ECE-1 gene is expressed by both endothelial and steroidogenic cells; however, the intracellular ECE-1a isoform was present only in ET-1-expressing endothelial cells [4].
• This study was undertaken to investigate the hormonal regulation and cell-specific expression of ECE-1 isoforms in endothelial and steroidogenic cells of bovine follicles and corpora lutea (CL) [4].
• Effect of an antisense oligodeoxynucleotide to endothelin-converting enzyme-1c (ECE-1c) on ECE-1c mRNA, ECE-1 protein and endothelin-1 synthesis in bovine pulmonary artery smooth muscle cells [8].
• Here, we describe the characterization of ECE-1 isoforms in bovine pulmonary artery smooth muscle cells (BPASMC) and the effect on ET-1 synthesis of an antisense oligodeoxynucleotide (ODN) to ECE-1c [8].
• Also, we demonstrated that a cell line, CHO-K1, showed no detectable activity of endothelin converting enzyme [9].

Associations of ECE1 with chemical compounds

• Co-expression of the cloned cDNA of bovine ECE with human preproET-1 cDNA in CHO-K1 cells resulted in the production of mature ET-1 and this production was inhibited by phosphoramidon [5].
• Treatment with chlorophenyl-thio cyclic AMP (200 microM) for 24 h decreased ECE-1 and -2 expression to approximately 50% and approximately 40% of the control value, respectively [10].
• These increases in ECE-1 and -2 expression with TPA were inhibited by cotreatment with calphostin C (10(-7) M) [10].
• Treatment of BPASMC with a phosphorothioate antisense ODN to ECE-1c caused a marked reduction in ECE-1c mRNA levels and ECE-1 protein levels [8].
• We have established a novel method of molecular cloning of endothelin converting enzyme, a key enzyme in the production of a potent vasoconstrictor endothelin-1, by modification of the reverse hemolytic plaque assay [9].

Regulatory relationships of ECE1

• Effects of endothelin-converting enzyme inhibitors on hemolysate-induced morphological changes and production of endothelin-1 in bovine cerebrovascular endothelial cells [11].

Other interactions of ECE1

• Analyses of chimeric ECE-1/transferrin receptors demonstrate that the cytoplasmic tail of bovine ECE-1a is sufficient for the lysosomal delivery and rapid degradation [12].
• Ribonuclease protection assay revealed the expression of ECE-1 and -2 in cultured GEN, and the expression was increased approximately 2.5- and approximately 1.8-fold, respectively, by treatment with 10(-7) M 12-O-tetradecanocyl-phorbol-13-acetate (TPA) for 4 hours [10].

Analytical, diagnostic and therapeutic context of ECE1

• The novel protein, designated ECE-1 sv, has an apparent molecular mass of 75 kDa; by using site-directed mutagenesis its start site was identified in a region common to all ECE-1 forms suggesting that ECE-1 b-d SV mRNAs are translated into the same protein [3].
• Northern blot analysis revealed that ECE mRNA was abundantly expressed in lung [5].
• Sequencing of cloned ECE-1 cDNA products and semiquantitative RT-PCR demonstrated that ECE-1b and ECE-1c were expressed in BPASMC, with ECE-1c being the predominant isoform [8].
• The ECE-1 and ET(A) proteins were evaluated by semiquantitative Western blot analysis [13].
• Genetic transfer of endothelin converting enzyme activity to CHO-K1 cells: detection of positive cells by reverse hemolytic plaque assay [9].

References