Heterodimerization of endothelin-converting enzyme-1 isoforms regulates the subcellular distribution of this metalloprotease.

Endothelin-converting enzyme (ECE) is a membrane metalloprotease that generates endothelin from its direct precursor big endothelin. Four isoforms of ECE-1 are produced from a single gene through the use of alternate promoters. These isoforms share the same extracellular catalytic domain and contain unique cytosolic tails, which results in their specific subcellular targeting.

Piperidine renin inhibitors: from leads to drug candidates.

Non-peptidomimetic renin inhibitors of the piperidine type represent a novel structural class of compounds potentially free of the drawbacks seen with peptidomimetic compounds so far. Synthetic optimization in two structural series focusing on improvement of potency, as well as on physicochemical properties and metabolic stability, has led to the identification of two candidate compounds 14 and 23. Both display potent and long-lasting blood pressure lowering effects in conscious sodium-depleted marmoset monkeys and double transgenic rats harboring both the human angiotensinogen and the human renin genes.

Involvement of the endothelin system in experimental critical hind limb ischemia.

Background: Endothelin- (ET-1) is involved in the pathogenesis of several ischemic diseases. We investigated the hypotheses that ET-1 is involved in the pathogenesis of experimental critical hind limb ischemia and that ET-1 receptor antagonists have a protective effect.

Materials And Methods: Critical hind limb ischemia was achieved by exclusion of the femoral artery and embolization of collateral vessels in rats.

The endothelin system in human glioblastoma.

Endothelin-1 (ET-1) is a powerful mitogenic and/or anti-apoptotic peptide produced by many cancer cells. To evaluate the potential role of the endothelin system in glioblastoma we first determined the cellular distribution of the mRNA and proteins of the components of the endothelin system, preproendothelin-1 (PPET-1), endothelin-converting enzyme-1 (ECE-1), and ET(A) and ET(B) receptors in human glioblastoma tissue and glioblastoma cell lines. PPET-1, ECE-1, and ET(A) receptor were highly expressed in glioblastoma vessels and in some scattered glioblastoma areas whereas ET(B) receptor was mainly found in cancer cells.

Expression of the endothelin-converting enzyme-1 isoforms in endothelial cells.

The transformed human endothelial cell line EA.hy926 is commonly used for studying in vitro different aspects of endothelial cell biology such as signal transduction, expression or angiogenesis. These cells have the ability to process big endothelin (big-ET) into endothelin (ET), and express the endothelin-converting enzyme ECE-1.