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)

Antibodies raised in rabbits to detergent-solubilized pig kidney microvillar proteins have been used to investigate the membrane hydrolases by crossed immunoelectrophoresis. Eight enzymes were detected by specific staining methods: aminopeptidase M, dipeptidylpeptidase IV, neutral endopeptidase, aminopeptidase A, carboxypeptidase P, gamma-glutamyltransferase, trehalase and phosphodiesterase I. The mobility of all these enzymes, with the exception of trehalase and neutral endopeptidase, was increased by treatment of the detergent-solubilized preparation with papain. The difference between the detergent and proteinase forms of these enzymes is attributed to the removal of a small, non-antigenic peptide to which detergent is bound in significant quantities. This interpretation was further supported by experiments in which the microvillus fraction was labelled with an intramembrane photolabelling reagent, 1-azido-4-[125I]iodobenzene. After photolysis, the radioactivity in the membrane could be solubilized by detergent treatment but not by papain treatment. Radioautography after crossed charge-shift immunoelectrophoresis showed a good correlation between charge-shift (signifying the presence of detergent bound to a hydrophobic domain) and the presence of the label.
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PMID:Proteins of the kidney microvillar membrane. Immunoelectrophoretic analysis of the membrane hydrolases: identification and resolution of the detergent- and proteinase-solubilized forms. 48 90

The ectoenzymes acting in the metabolism of peptides play an essential role in renal cell-cell communication. We have studied four of these ectoenzymes, aminopeptidases N and A (APN, APA), dipeptidylpeptidase IV (DPP IV) and neutral endopeptidase (NEP) in cultured human glomerular mesangial and epithelial cells and cultured rabbit renal cortical vascular smooth muscle cells. APN is present at the surface of both mesangial and epithelial cells with identical characteristics. Its expression (enzyme activity and immunoreactive protein) is induced by phorbol-esters and other protein kinase C-stimulating agents. APA is present only in glomerular epithelial cells. Its expression is induced by glucocorticoids and cyclic AMP-stimulating agents. DPP IV is also present only in glomerular epithelial cells. Its expression (enzyme activity, immunoreactive protein and mRNA) is induced by interferon gamma. NEP is present in glomerular epithelial cells and vascular smooth muscle cells. The expression of the latter enzyme is inhibited in the presence of serum via the combined effect of Ca2+i and PKC-stimulating agents. In contrast, glucocorticoids and cyclic GMP induce its expression. NEP plays a major role in the catabolism by these cells of atrial natriuretic factor. All these data emphasize the multiplicity of the mechanisms controlling ectopeptidase expression in cultured glomerular and renal vascular cells.
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PMID:[Ectoenzymes of peptidic metabolism in renal glomerular and vascular cells]. 133 92

The effects of a range of metallopeptidase inhibitors on the activities of the porcine kidney cell surface zinc aminopeptidases, aminopeptidase A (AP-A; EC 3.4.11.2), aminopeptidase N (AP-N; EC 3.4.11.7) and aminopeptidase W (AP-W; EC 3.4.11.16), have been directly compared. Amastatin and probestin were effective against all three aminopeptidases, with the concentration of inhibitor required to cause 50% inhibition (I50) in the low micromolar range (I50 = 1.5-20 microM), except for probestin with AP-N which displayed an I50 of 50 nM. Actinonin failed to inhibit significantly either AP-A or AP-W, and thus can be considered a relatively selective inhibitor (I50 = 2.0 microM) of AP-N. In contrast, bestatin was a relatively poor inhibitor of AP-N (I50 = 89 microM) and failed to inhibit AP-A, but was more potent towards AP-W (I50 = 7.9 microM). Thus, some of the observed chemotherapeutic actions of bestatin may be due to inhibition of cell-surface AP-W. A number of other metallopeptidase inhibitors, including inhibitors of endopeptidase-24.11 (EC 3.4.24.11) and membrane dipeptidase (EC 3.4.13.11), and the carboxylalkyl and phosphoryl inhibitors of angiotensin converting enzyme (EC 3.4.15.1) failed to inhibit significantly AP-A, AP-N or AP-W. However, AP-W was inhibited with I50 values in the micromolar range by the sulphydryl converting enzyme inhibitors rentiapril (I50 = 1.6 microM), zofenoprilat (I50 = 7.0 microM) and YS 980 (I50 = 17.7 microM). Neither AP-A nor AP-N were affected by these sulphydryl compounds. Inhibition of AP-W may account for some of the side effects noted with the clinical use of the sulphydryl converting enzyme inhibitors. The availability of compounds which are totally selective for AP-W over any of the other mammalian cell surface zinc aminopeptidases may aid in identifying endogenous substrates, and thus physiological or pathophysiological role(s) of AP-W.
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PMID:Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme. 136 Feb 11

Aminopeptidase inhibitors have been demonstrated to enhance the behavioral effects of both exogenously applied and endogenously released neuropeptides. In this study peptidase inhibitors were used as probes for involvement of central neuropeptides in osmotically-induced drinking behavior. Intracerebroventricular (i.c.v.) injections of amastatin, an aminopeptidase A inhibitor, potentiated water intake induced by subcutaneous injections of hypertonic saline. Drinking responses to i.c.v. infusions of hypertonic saline were also enhanced when amastatin was added to the infusions. The effect was not attenuated by the angiotensin receptor antagonist, [Sar1, Thr8]angiotensin II, which suggests that angiotensins do not play a role in the over-drinking. Drinking responses to centrally infused hypertonic saline were not enhanced by i.c.v. thiorphan, an endopeptidase inhibitor; this provides evidence that the effects of amastatin are specific for a particular class of peptidases. These results suggest that there is a role for an endogenous, non-angiotensinergic brain peptide in the mediation of osmotic thirst.
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PMID:Amastatin potentiates drinking elicited by osmotic stimuli: evidence for peptidergic mediation of intracellular dehydration-induced thirst. 142 35

A comprehensive survey of 11 peptidases, all of which are markers for renal microvillar membranes, has been made in membrane fractions prepared from pig choroid plexus. Two fractionation schemes were explored, both depending on a MgCl2-precipitation step, the preferred one having advantages in speed and yield of the activities. The specific activities of the peptidases in the choroid-plexus membranes were, with the exception of carboxypeptidase M, lower than in renal microvillar membranes: those of aminopeptidase N, peptidyl dipeptidase A ('angiotensin-converting enzyme') and gamma-glutamyltransferase were 3-5-fold lower, those of aminopeptidase A and endopeptidase-24.11 were 12-15 fold lower, and those of dipeptidyl peptidase IV and aminopeptidase W were 50-70-fold lower. Carboxypeptidase M had a similar activity in both membranes. Alkaline phosphatase and (Na+ + K+)-activated ATPase were more active in the choroid-plexus membranes. No activity for microsomal dipeptidase, aminopeptidase P and carboxypeptidase P could be detected. Six of the peptidases and (Na+ + K+)-activated ATPase were also studied by immunoperoxidase histochemistry at light- and electron-microscopic levels. Endopeptidase-24.11 and (Na+ + K+)-activated ATPase were uniquely located on the brush border, and the other two peptidases appeared to be much more abundant on the endothelial lining of microvessels. Dipeptidyl peptidase IV and aminopeptidase W were also detected in microvasculature. Pial membranes associated with the brain and spinal cord also stained positively for endopeptidase-24.11, aminopeptidase N and peptidyl dipeptidase A. The immunohistochemical studies indicated the subcellular fractionation did not discriminate between membranes derived from epithelial cells (i.e. microvilli) and those from endothelial cells. The possible significance of these studies in relation to neuropeptide metabolism and the control of cerebrospinal fluid production is discussed.
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PMID:Membrane peptidases in the pig choroid plexus and on other cell surfaces in contact with the cerebrospinal fluid. 265 79

Porcine cerebral microvessels were isolated by differential sieving and centrifugation and were characterized by microscopic examination and marker enzyme enrichment (gamma-glutamyltransferase; EC 2.3.2.2). Purified microvessels contained a membrane-bound enzyme immunologically indistinguishable from renal aminopeptidase A (AmA; EC 3.4.11.7). AmA hydrolyzed both alpha-glutamyl- and alpha-aspartyl-2-naphthylamide, and hydrolysis was competitively inhibited by angiotensin II. Micro-vessel AmA hydrolyzed the N-terminal Asp1-Arg2 bond of both angiotensin I and angiotensin II, whereas the angiotensin II antagonist saralasin [(Sar1, Ala8)angiotensin II] was resistant to N-terminal hydrolysis. Angiotensin metabolism was optimal at pH 8.5 and was inhibited by EDTA, o-phenanthroline and amastatin. Conversely, inhibitors of neutral endopeptidase (phosphoramidon), post-proline cleaving enzyme (Z-Pro-Prolinal), carboxypeptidase N [D-L-mercaptomethyl-3-guanidinoethylthiopropanoic acid (MERGETPA)] and angiotensin I converting enzyme (captopril) had no effect. The Km values of angiotensin I, angiotensin II and (Asn1, Val5)angiotensin II for microvessel AmA were 40.1 +/- 8.2, 35.3 +/- 4.3 and 156 +/- 22 microM respectively. Cerebral microvascular aminopeptidase A may play a role in vivo in modulating angiotensin-mediated local cerebral blood flow, and in preventing circulating angiotensins from crossing the blood-brain barrier.
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PMID:Angiotensin metabolism by cerebral microvascular aminopeptidase A. 289 20

In the present study, we established a dependable system by which human pre-B- and non-T/non-B-acute lymphoblastic leukemia (ALL) cells are efficiently transplanted into nude mice; the transplanted tumors provide a useful model for investigating the efficacy of antitumor agents in the in vivo therapy of human cancer. NALM-6 (a pre-B-ALL cell line) cells were transplanted under varying conditions as the pre-B-leukemia cells, whereas REH (a non-T/non-B-ALL cell line) cells were transplanted as the non-T/non-B-leukemia cells. Under optimal and near optimal conditions, 71 of 101 X-irradiated mice (70%) developed distinct tumors approximately 2 wk after i.d. inoculation of a mixture of NALM-6 cells and X-irradiated human fibrosarcoma cells. Under the same conditions, 9 of 11 mice (82%) developed tumors following i.d. inoculation of REH cells admixed with X-irradiated human fibrosarcoma cells. Examination of the tumor tissues demonstrated that the tumors are of leukemia origin but not of fibrosarcoma origin. To demonstrate the usefulness of the present tumors for investigating the efficacy of antitumor agents in the in vivo therapy of human cancer, immunotoxins were tested for their specific suppressive activity against growing tumors of the transplanted NALM-6 cells. To this end, monoclonal antibodies SN5 and SN6 which define a common ALL antigen, termed CALLA, and a novel leukemia-associated cell surface glycoprotein, termed gp160, respectively, were separately conjugated with the A-chain subunit of ricin, a plant toxin; CALLA and gp160 are expressed on the cell surface of various human non-T-leukemia cells including NALM-6 cells. The conjugates of SN5 and SN6 with ricin A-chain (RA) showed specific activity against the leukemia cells but not against control cells in an in vitro assay. To investigate their in vivo efficacy in suppressing tumor growth, nude mice which had been inoculated i.d. with NALM-6 cells 25 days in advance and bore distinct palpable tumors (5 to 6 mm in diameter) were divided into five groups. One group of mice was nontreated as a control. Each of the remaining four groups of mice was given an injection of one of the following agents: (a) purified control mouse IgG (IgG1); (b) purified antibodies SN5 (IgG1) and SN6 (IgG1); (c) control IgG-RA conjugate; or (d) SN5-RA and SN6-RA. Tumors in all mice of the first four groups including the untreated group grew continuously, causing the mice to die.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Efficient transplantation of human non-T-leukemia cells into nude mice and induction of complete regression of the transplanted distinct tumors by ricin A-chain conjugates of monoclonal antibodies SN5 and SN6. 296 82

Five membrane peptidases were studied by radiation inactivation analysis of pig kidney microvillar membranes. One heterodimeric enzyme, gamma-glutamyl transferase, presented a target size corresponding to the dimeric Mr. The other enzymes are known to be homodimers. Three of these, aminopeptidase A. aminopeptidase N and dipeptidyl peptidase IV, gave results clearly indicating the monomer to be the target and, hence, in this group the association of the subunits was not essential for activity. The target size for endopeptidase-24.11 was intermediate between those for monomer and dimer and its functional state was not resolved by the experiments.
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PMID:Radiation inactivation analysis of kidney microvillar peptidases. 352 52

Microvilli from human placental syncytiotrophoblast are rich in angiotensin I converting enzyme (ACE), aminopeptidase A, a carboxypeptidase N-like enzyme, and a neutral endopeptidase (NEP). The specific activities of these enzymes were enhanced in microvillus-enriched fractions obtained by differential centrifugation: Purified microvilli were isolated in a discontinuous sucrose gradient. The placental microvilli hydrolyzed angiotensin II, vasopressin and oxytocin as shown by high pressure liquid chromatography. The inhibitors, bestatin, phosphoramidon, and o-phenanthroline, established the specificity of the enzymes. Aminopeptidase A (angiotensinase A) cleaved angiotensin II to angiotensin III and Asp1. NEP from placenta and from human kidney hydrolyzed oxytocin at the Pro7-Leu8 bond to yield oxytocin 1-7 and leucyl-glycine amide, but did not hydrolyze vasopressin. Vasopressin was cleaved by aminopeptidases in the placental membranes. On electroblotting placental NEP appeared as a double band with a molecular weight slightly higher than the 90,000 of the purified kidney enzyme. Neuraminidase treatment reduced the molecular weight of the placental enzyme to approximately 90,000, indicating that it contains a large amount of sialic acid. The microvilli of human placenta are thus rich in enzymes that may regulate passage of peptides at the maternal-fetal interface.
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PMID:Enzymes in placental microvilli: angiotensin I converting enzyme, angiotensinase A, carboxypeptidase, and neutral endopeptidase ("enkephalinase"). 609 76

An organ culture employing slices of renal-cortex tissue from piglets of the Yucatan strain was used to study the biogenesis of four microvillar peptidases: endopeptidase-24.11 (EC 3.4.24.11), dipeptidyl peptidase IV (EC 3.4.14.5), aminopeptidase N (EC 3.4.11.2) and aminopeptidase A (EC 3.4.11.7). The viability of the culture system was confirmed by the preservation of ultrastructural integrity and by an unchanged uptake of [3H]alanine into cells during the period of the experiments. After labelling with [35S]methionine, treatment with Mg2+ yielded two fractions, one containing microvilli and another, the Mg2+ pellet, containing intracellular and basolateral membranes. The labelled forms of the peptidases, isolated by immunoprecipitation, were analysed by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and fluorography. The Mg2+ pellet contained the earliest detectable forms of the enzymes. In each case, a polypeptide of lower Mr than the mature form and sensitive to treatment with endo-beta-N-acetylglucosaminidase H was the first form to be detected. These high-mannose forms were followed, about 30 min after the pulse, by a complex glycosylated form of higher Mr. Only the latter form was observed in microvilli and then only after 90 min of the chase period. A quantitative study of dipeptidyl peptidase IV showed that the forms observed in the Mg2+ pellet were precursors of those in the microvillar fraction. No labelled forms were observed in the cytosol. All four peptidases were thus synthesized within membrane compartments and glycosylated in two steps before assembly in microvilli.
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PMID:Proteins of the kidney microvillar membrane. Biosynthesis of endopeptidase-24.11, dipeptidylpeptidase IV and aminopeptidases N and A in pig kidney slices. 615 93


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