Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endopeptidase-24.18 (endopeptidase-2, EC 3.4.24.18, E-24.18) is a Zn-ectoenzyme of rat renal and intestinal microvillar membranes exhibiting an oligomeric structure, alpha 2-beta 2. The primary structure of the alpha-subunit of E-24.18 has been defined by molecular cloning and its expression mapped in rat kidney by in situ hybridization. A 2.9-kb cDNA coding for the alpha-subunit was isolated and sequenced. It had an open reading frame of 2,244 base pairs coding for a type I membrane protein of 748 amino acids. The deduced amino acid sequence showed 87% identity with that of meprin A, a mouse metallo-endopeptidase, sharing common properties with the rat enzyme, and 85% identity with the human intestinal enzyme, 'PABA-peptide hydrolase'. Northern blot analysis revealed the alpha-subunit to be encoded by a single mRNA species of 3.2-kb. In situ hybridization performed on rat kidney showed a co-localization of E-24.18 with endopeptidase-24.11 in proximal tubules of juxtamedullary nephrons, suggesting that the two enzymes have similar or complementary physiological functions in kidney.
FEBS Lett 1992 Sep 07
PMID:Molecular cloning of the alpha-subunit of rat endopeptidase-24.18 (endopeptidase-2) and co-localization with endopeptidase-24.11 in rat kidney by in situ hybridization. 150 84

Hydrolysis of endothelin 1 by rat kidney membranes was investigated using a reverse-phase HPLC and an automated gas-phase protein sequencer. Endothelin 1 was hydrolyzed into four major fragments which were detected by HPLC. Phosphoramidon, an inhibitor of neutral endopeptidase 24,11, almost completely suppressed the production of three fragments, but one fragment was not affected by the inhibitor. Analysis of N-terminal sequences of the degradation products revealed that the phosphoramidon-sensitive fragments were generated by cleavage at the Ser5-Leu6 bond of endothelin 1 that was identical with its cleavage site by purified rat endopeptidase 24,11, reported previously. The phosphoramidon-insensitive fragment was produced by cleavage at Leu17-Asp18, which was distinct from the sites by endopeptidase 24,11, but corresponded to that by a phosphoramidon-insensitive metallo-endopeptidase recently isolated from rat kidney membranes by us [(1992) Eur. J. Biochem. 204, 547-552]. Kinetic determination of endothelin 1 hydrolysis by the isolated enzyme yielded values of Km = 71.5 microM and kcat = 1.49 s-1, giving a ratio of kcat/Km = 2.08 x 10(4) s-1.M-1. The Km value was much higher and the kcat/Km value was much lower than those for rat endopeptidase 24,11 reported previously. Thus, endopeptidase 24,11 appears to hydrolyze endothelin 1 more efficiently than the isolated enzyme does. Both enzymes may play physiological roles in the metabolism of endothelin 1 by rat kidney membranes in vivo.
FEBS Lett 1992 Sep 14
PMID:Endothelin 1 hydrolysis by rat kidney membranes. 151 1

We developed a fluorometric assay for endopeptidase-24.11 (EC 3.4.24.11) in human plasma. Substrate [glutaryl-Ala-Ala-Phe-amidomethylcoumarin(AMC)] was incubated with plasma (20 microL, 30 min, pH 7.6) with (control) or without the endopeptidase-24.11 inhibitor phosphoramidon. Further incubation with aminopeptidase M released free AMC. Within-assay CVs were 4.5% and 8.6%, respectively, at 3.31 and 0.27 nmol of AMC released per milliliter per minute. The between-assay CV was 10.4% at 0.31 nmol/mL per minute and the detection limit was 0.05 nmol/mL per minute. A highly skewed distribution of endopeptidase-24.11 in 41 normal samples was found, ranging from 0.12 to 6.84 nmol/mL per minute (median = 0.44). Mean endopeptidase-24.11 concentrations were significantly higher in hypertensive subjects (0.68 nmol/mL per minute) than in normotensive subjects (0.34 nmol/mL per minute; P less than 0.05). Compared with placebo administration, the oral endopeptidase-24.11 inhibitor UK 79300 significantly inhibited the plasma enzyme at doses of 100 mg (twice daily). Although in normotensive subjects the enzyme was unaffected with doses of 25 mg, the same dose (25 mg) inhibited the plasma enzyme in hypertensive subjects. No activity was detected in sheep plasma, but addition of exogenous endopeptidase-24.11 to sheep plasma in vitro allowed in vivo assessment of the effect of infused endopeptidase-24.11 inhibitor SCH 39370.
Clin Chem 1992 Sep
PMID:Assay of endopeptidase-24.11 activity in plasma applied to in vivo studies of endopeptidase inhibitors. 152 15

Thiorphan, a potent inhibitor of enkephalinase (membrane metalloendopeptidase, atriopeptidase, EC 3.4.24.11) enhanced markedly (+214%) and prolonged the rise in plasma atrial natriuretic factor (ANF) immunoreactivity in anesthetized rats submitted to acute extracellular volume expansion obtained through i.v. injection of a Ringer's solution. These changes were accompanied by marked potentiations of the natriuretic and diuretic responses to the ANF-releasing stimulus, whereas kaliuresis was only slightly affected. Thiorphan also enhanced markedly the biphasic rise in urinary cyclic GMP excretion elicited by volume expansion. All these renal responses to volume expansion in thiorphan-treated rats were significantly reduced by pretreatment with anti-ANF antibodies, suggesting an involvement of the endogenous natriuretic hormone protected against degradation. However, pretreatment with antibradykinin antibodies led to qualitatively similar results, suggesting that the endogenous kinin-generating system in kidney may also participate in the responses to endogenous ANF and their potentiation by the peptidase inhibitor.
J Pharmacol Exp Ther 1991 Sep
PMID:Thiorphan-induced natriuresis in volume-expanded rats: roles of endogenous atrial natriuretic factor and kinins. 165 39

We investigated the origin of leukemic progenitors in a case of the simultaneous occurrence of myelomonocytic leukemia and multiple myeloma (IgG-kappa). At presentation, myeloperoxidase and nonspecific esterase-positive myelomonocytic cells had proliferated up to 12.2 x 10(9)/liter in the peripheral blood. Bone marrow cell differentials revealed the coexistence of myelomonocytic cells (30%) and atypical plasmacytoid cells (26%). Myelomonocytic cells in peripheral blood expressed both myeloid antigens (CD11b, CD13, CD14, CD15, CD33) and T/B-lymphoid antigens (CD2, CD4, CD5, CD7, CD10, PCA-1). Bone marrow mononuclear cells (BMMC) could be divided into PCA-1 strongly positive and PCA-1 weakly positive populations, which were considered to represent myeloma cells and myelomonocytic cells, respectively; the former were CD2-positive (CD2+), CD14-, and CD15-, whereas the latter were CD2+, CD14+, and CD15+. Immunohistochemical analysis revealed that, in addition to plasmacytoid cells, a minority of myelomonocytic cells showed a positive reaction for IgG staining, and production of IgG was observed in the culture supernatant of CD14+ myelomonocytic cells in peripheral blood. Southern blot analysis revealed the presence of two identical rearrangement bands of immunoglobulin heavy chain gene in both BMMC containing myeloma cells and myelomonocytic cells and CD14+ myelomonocytic cells in peripheral blood. In a long-term methylcellulose assay, peripheral blood mononuclear cells produced large compact colonies consisting of macrophages and IgG+ plasmacytoid cells (M phi/P colonies), while BMMC produced a different type of colonies consisting of CD14+ myelomonoblasts, macrophages, and IgG+ plasma cells (Mb/M phi/P colonies) in addition to M phi/P colonies. Recloning experiments showed that primary Mb/M phi/P colonies gave rise to both secondary M phi/P and Mb/M phi/P colonies. These observations strongly suggest that common leukemic progenitors provide both myeloma and myelomonocytic leukemia cells, and the mechanism of "lineage infidelity" is probably involved in the development of their "bilineal" differentiation.
J Cell Physiol 1991 Sep
PMID:Simultaneous occurrence of myelomonocytic leukemia and multiple myeloma: involvement of common leukemic progenitors and their developmental abnormality of "lineage infidelity". 165 17

An immunofluorescence study of the adherent layer of human long-term bone marrow cultures (HLTBMC) revealed the following surface markers on the different stromal cell populations: stromal fibroblastic cells CD10+, FIB86.3+, CD13+, CD71+; adipocytes CD10+, FIB86.3-, CD13+, CD71-/+; and macrophages CD10-/+, FIB86.3+, CD13+, CD71-/+, CD14+, CD33+, CD25+, HLA-DR+, CD4+, CD19+, CD45+. The markers of the stromal fibroblastic cells in HLTBMC were similar to those of twice-passaged fibroblasts not only from bone marrow and spleen, but also from a hemopoietic non-supportive organ such as the skin. Some of the cultured human umbilical vein endothelial cells used as controls were found to be CD25+, demonstrating for the first time the interleukin-2 receptor p55 chain on normal non-hemopoietic cells. The stromal fibroblastic cells are overrepresented compared to the small non-macrophage hemopoietic cell population in the adherent layer of HLTBMC. In addition, silver staining revealed an increased reticulin content in most of the HLTBMC. An excessive growth of stromal fibroblastic cells and an excessive deposition of their product, the reticulin fibers, are the hallmark of myelofibrosis. The finding of equivalent observations in HLTBMC suggests that the hitherto unexplained, premature quenching of hemopoiesis in HLTBMC might at least partly be due to mechanisms similar to those operating in myelofibrosis in vivo.
Leukemia 1991 Sep
PMID:Stromal populations and fibrosis in human long-term bone marrow cultures. 165 97

An inhibitor (BGIA) against an acidic amino acid-specific endopeptidase of Streptomyces griseus (Glu S. griseus protease) was isolated from seeds of the bitter gourd Momordica charantia L., and its amino acid sequence was determined. The molecular weight of BGIA based on the amino acid sequence was calculated to be 7419. BGIA competitively inhibited Glu S. griseus protease with an inhibition constant (Ki) of 70 nM, and gel filtration analyses suggested that BGIA forms a 1:1 complex with this protease. However, two other acidic amino acid-specific endopeptidases, protease V8 from Staphylococcus aureus and Bacillus subtilis proteinase (Glu B. subtilis protease), were not inhibited by BGIA. BGIA had no inhibitory activity against chymotrypsin, trypsin, porcine pancreatic elastase, and papain, although subtilisin Carlsberg was strongly inhibited. The amino acid sequence of BGIA shows similarity to potato chymotrypsin inhibitor, barley subtilisin-chymotrypsin inhibitor CI-1 and CI-2, and leech eglin C, especially around the reactive site. Although the residue at the putative reactive site of these inhibitors is leucine or methionine, the corresponding amino acid in BGIA is alanine.
J Biol Chem 1991 Sep 05
PMID:Purification and amino acid sequence of a bitter gourd inhibitor against an acidic amino acid-specific endopeptidase of Streptomyces griseus. 167 33

Cell surface peptidases degrade enkephalins and thereby restrict the number of molecules available to activate receptors. The effects of peptidase inhibitors on degradation of enkephalins and on enkephalin-stimulated contraction of gastric smooth muscle cells were examined. Muscle cells dispersed from the guinea pig stomach degraded [Tyr1-3H] [Leu5]enkephalin (41.6 +/- 9.0% degradation at 60 min incubation, mean +/- SD, n = 4 animals). Amastatin (10 microM, an aminopeptidase inhibitor) inhibited degradation by 72.1 +/- 1.5% The residual peptidase activity was inhibited by phosphoramidon (1 microM, an endopeptidase EC 3.4.24.11 inhibitor) by 58.0 +/- 11.0%. [Tyr1-125I] [Met5]enkephalin was similarly degraded. Phosphoramidon (1 microM) inhibited the degradation of the aminopeptidase-resistant peptide [Tyr1-3H] [D-Ala2]-[Leu5]enkephalin by greater than 95%. [Met5]enkephalin, incubated with cells for 30 s, stimulated contraction [50% maximal contraction (EC50) 120 +/- 50 nM, n = 6]. Pretreatment of cells with phosphoramidon alone, amastatin alone, or phosphoramidon plus amastatin, caused 20-fold (EC50 6.5 +/- 1.1 nM), 2-fold (EC50 63 +/- 23 nM), and 100-fold (EC50 1.1 +/- 0.3 nM) increase in potency of [Met5]enkephalin, respectively. The results show that endopeptidase EC 3.4.24.11 and aminopeptidases contribute to degradation of enkephalins by gastric muscle cells. The rapidity and magnitude of the potentiating effects of the inhibitors on enkephalin-stimulated contraction suggest a close physical relationship between the peptidases and the enkephalin receptors.
Am J Physiol 1991 Sep
PMID:Inhibition of peptidases potentiates enkephalin-stimulated contraction of gastric muscle cells. 167 1

Most of the circulating lymphocytes from three asymptomatic adults (one male, two female, age range 61-67 years) with isolated persistent lymphocytosis of between 7.1 and 10 x 10(9)/l possessed characteristic villous projections of the cell membrane. Morphological, histochemical, ultrastructural, immunological, and genotypic studies confirmed a clonal proliferation of tartrate-resistant acid phosphatase (TRAP)-negative CD5-CD10-CD25- and CD11c+ B-cells. In addition to CD11c, these cells expressed other adhesion receptors (LFA-1/CD11a, VLA-4/CD29/49d, ICAM-1/CD54, and LAM-1) and produced detectable amounts of interleukin-1 beta, interleukin-6, and in one case tumour necrosis factor-alpha mRNA. This monoclonal villous lymphocytosis (MVL) could be differentiated from B-cell chronic lymphocytic, prolymphocytic, and hairy cell leukaemias, and from previously recognized CD11c+ chronic B-cell leukaemia. A rare splenomegalic non-Hodgkin's lymphoma variant with circulating villous B-lymphocytes (SLVL), usually CD10+ and sometimes CD11c- and TRAP+, appears to be a closely related disorder. In all three patients the lymphocyte count increased very slowly, at a rate less than 5 x 10(9)/l per year, over 3-7.5 years of follow up, and a moderate splenomegaly eventually developed in one of the patients. Chemotherapy was never required. MVL may be a relatively benign clinical entity akin to SLVL within the group of CD11c+ B-cell lymphoproliferative disorders.
Leukemia 1991 Sep
PMID:Monoclonal lymphocytosis with villous lymphocytes: a chronic lymphoproliferative disease of CD11c+ B-cells. 168 36

The content of membrane peptidases has been compared in the human astrocytoma clone D384 and the human neuroblastoma line SH-SY5Y. Endopeptidase-24.11 (neutral endopeptidase, EC 3.4.24.11) was detectable only on the astrocytoma cells whereas angiotensin-converting enzyme (EC 3.4.15.1) was selectively expressed on the neuroblastoma line. Dipeptidyl peptidase IV (EC 3.4.14.5) was also abundant on the astrocytoma line. The presence of both endopeptidase-24.11 and dipeptidyl peptidase IV on D384 cells was confirmed by immunohistochemistry. A membrane preparation from D384 cells hydrolyzed both atrial natriuretic peptide and brain natriuretic peptide and, in both cases, the pattern of metabolism was similar to that seen with purified endopeptidase-24.11. The endopeptidase-24.11 inhibitor, phosphoramidon, at 1 microM abolished natriuretic peptide metabolism. The neuroblastoma line, which lacked endopeptidase-24.11, failed to metabolise atrial natriuretic peptide and brain natriuretic peptide, emphasizing the key role of the endopeptidase in hydrolyzing these regulatory peptides at the cell surface.
Neuroendocrinology 1991 Sep
PMID:Hydrolysis of atrial and brain natriuretic peptides by the human astrocytoma clone D384 and the neuroblastoma line SH-SY5Y. 168 34


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