High impact information on ECE2

• Optimal ECE activity was measured at pH 6.0, a value intermediate between that reported for ECE-1 (pH 6.8) and ECE-2 (pH 5.5), indicating expression of both enzymes [1].
• Confocal microscopy revealed a punctate pattern of ECE-2-like immunoreactive staining in the cell cytosol, suggesting localization to secretory vesicles with a possible role in processing big ET-1 while in transit to the cell surface via the constitutive secretory pathway [1].
• Evidence for intracellular endothelin-converting enzyme-2 expression in cultured human vascular endothelial cells [1].
• 4 (IC50 1.5 nmol/L), consistent with ECE-2 activity [1].
• Of the other genes, PPET-2 and ET(B) were expressed in all tissue specimens and no differences were observed between tumor subtypes or tumor-affected and normal tissue specimens, whereas PPET-3 and ECE-2 were present in all tissue specimens but were barely detectable [2].

Biological context of ECE2

• Because of the previously reported human genetic diseases ascribed to germline mutations of member genes of the endothelin family, ECE2 was localized in human chromosomes with fluorescence in situ hybridization and radiation hybrid mapping to 3q28-q29 and SHGC-20171/D3S1571, respectively [3].
• Isolation of human ECE-2 (EC 3.4.24.71) cDNAs revealed deduced open reading frames of 787 and 765 amino acids with approximately 60% identity with human ECE-1 [3].

Anatomical context of ECE2

• In diseased vessels, ECE-1c, ECE-1b and ECE-2 antisera stained macrophages infiltrating atherosclerotic plaques within coronary arteries [4].
• Intense ECE-1b immunoreactivity was present within renal and pulmonary epithelial cells with lower levels of staining displayed by ECE-1c, ECE-1a and ECE-2 antisera [4].
• ECE-1b, ECE-1c and ECE-2 immunoreactivity was localized to perivascular astrocytes and neuronal processes in the cerebral cortex [4].

Regulatory relationships of ECE2

• These results suggest ECE-1b and ECE-2 may be widely expressed in normal tissue from humans and inhibition of ECE-1 isoforms and ECE-2 expressed by cells such as macrophages in pathophysiological tissue may be an additional therapeutic target in cardiovascular disease [4].

Other interactions of ECE2

• A second enzyme, ECE-2, also exists as four isoforms and differs from ECE-1 in requiring an acidic pH for optimal activity [5].

Analytical, diagnostic and therapeutic context of ECE2

• Our aim was to compare the cellular expression of endothelin-converting enzyme-1 (ECE-1) isoforms and ECE-2 using immunocytochemistry in normal and diseased human tissue [4].
• Based on immunoblotting, ECE-1 was detected only at the PM, whereas ECE-2 and cathpesins B and D were detected in the cytosol [6].

References