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)

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

Surface peptidase activities on the human monocytic lineage cell line U937 were characterized. Two diisopropyl phosphofluoridate (DFP)-inhibitable serine peptidases were identified by differences in their hydrolytic activities on chromogenic peptides: one removed tripeptides from the free NH2-terminal end of the synthetic peptide Ala-Ala-Phe-p-nitroanilide (pNA) and was not inhibited by inhibitors of metallo-, cysteic-, and aspartic-proteinases, or by those of elastase-, trypsin- and chymotrypsin-like enzymes, suggesting the presence of a hitherto unidentified serine tripeptidyl endopeptidase; the other peptidase catalyzed the release of Gly-Pro from Gly-Pro-pNA and was inhibited by DFP, phenylmethyl sulfonyl fluoride and diprotin A, thus resembling dipeptidyl peptidase IV (DPP IV) with respect to its substrate specificity and inhibitor profile. A group of N-exo-aminopeptidase activities specifically inhibited by bestatin, was also detected when Ala-, Leu-, Arg- and Lys-pNA were used a substrates. The activities were surface associated and not secreted as determined by extracellular location of product and enzymatic recovery in highly purified U937 cell membranes. Peripheral monocytes and macrophages were found to virtually exhibit identical levels of these two classes of peptidase activities when compared to those detected on U937 cells. The relative contributions of these hydrolytic enzymes to the cleavage of bioactive and radioiodinated cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha and interferon-gamma was next examined. The results indicated that N-aminopeptidases do not appear to participate in the catabolism of any tested cytokine. In contrast, the most interesting finding was that both serine peptidases participate in TNF-alpha degradation. Analysis of the final proteolytic digestion products demonstrated the disappearance of the native 17-kDa molecule TNF-alpha, and the concomitant release of biologically inactive fragments of less than or equal to 2 kDa. Together, these observations indicate new roles for both the DPP IV-like enzyme and the tripeptidyl endopeptidase located at the surface of human monocytic cells, including the regulation of the extracellular TNF-alpha concentration. Thus, the identification of functional ectopeptidases provides insight into their potential role in both normal and malignant monocytic function.
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PMID:Human U937 cell surface peptidase activities: characterization and degradative effect on tumor necrosis factor-alpha. 134 32

Plasma membranes (PM) were prepared by discontinuous density gradient centrifugation of crude nuclear fractions from 6 rat livers. These "nuclear" PM (PM-n) were 15-fold enriched in plasma membrane marker enzymes and contained an endopeptidase activity degrading azocasein at pH 7. To get larger amounts of plasma membranes, microsomal fractions obtained in large scale subcellular fractionations were subjected to continuous gradient zonal centrifugation. These "microsomal" PM (PM-m) were 22-fold enriched in 5'-nucleotidase, however, the separation of PM from endocellular membranes was not complete. PM-m showed endopeptidase activity degrading azocasein at pH 5.4 faster than at pH 7.5 and exopeptidases degrading Ala-Pro-pNA and Ala-pNA at pH 7.6. The latter two activities were distributed over the gradient similar to PM marker enzymes and can be solubilized by detergent and proteinase treatment. Therefore, dipeptidyl-aminopeptidase IV and Ala-aminopeptidase are intrinsic plasma membrane enzymes and can be used as additional markers for rat liver plasma membranes. The efficiency and selectivity to solubilize plasma membrane bound endopeptidase, DPP IV and aminopeptidase activities are compared.
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PMID:Proteolytic activities in plasma membrane preparations from rat liver. 1. Preparation of rat liver plasma membranes and solubilization of membrane bound proteases. 636 Jan 63

Plasma membranes (PM) were prepared from nuclear and microsomal fractions of rat liver as described in the preceding paper. Four different proteolytic activities were studied and found to be solubilized from PM fractions after detergent treatment: endopeptidase activity at neutral and acid pH, dipeptidyl-aminopeptidase IV, and (alanine-)aminopeptidase. Both PM preparations contain a serine-endopeptidase with optimal activity against azocasein at pH 7.6. After solubilization of PM derived from microsomal fractions (PM-m) and gel filtration this activity shows an apparent molecular mass of 220 +/- 20 kD. This membrane proteinase is different from other known serine proteinases of liver cells because of its large molecular mass and an activating effect of 1,10-phenanthroline. PM derived from microsomal fractions contain additional endopeptidase with a pH optimum of 5.2 that could be inhibited by 4-chloromercuribenzoate, leupeptin and Z-Phe-Ala-diazomethylketone. Using detergent solubilization and gel filtration this acid endopeptidase activity in PM-m can be resolved into three peaks with apparent molecular masses (detergent forms) of 180 +/- 10, 80 +/- 10 and 35 +/- 10 kD, the latter may be cathepsin L. In addition to the endopeptidases, PM-m were shown to contain also aminopeptidases degrading Ala-Pro-pNA and Ala-pNA. The former activity, dipeptidyl-aminopeptidase IV (DPP IV), has features similar to DPP IV from other microvillus membranes (inhibition by DIFP and PMSF, pH optimum at 7.7). The Ala-pNA degrading aminopeptidase is inhibited by chelating agents and some bivalent heavy metal ions, but is activated by Co++-ions. Both enzymes apparently were eluted as monomers (molecular mass 180-190 kD) after gel filtration in detergent containing buffers.
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PMID:Proteolytic activities in plasma membrane preparations from rat liver. 2. Partial purification and characterization of membrane bound endopeptidases, dipeptidyl-aminopeptidase IV and aminopeptidase. 636 Jan 64

Inter- and intralobular mammary fibroblasts have been separated from normal human breast tissue and cultured to study the differential expression of ectoenzymes present within the stroma of the normal gland and associated with breast cancers. Specific ectoenzymes were identified by indirect immunofluorescence and quantified by flow cytometry and semi-quantitative PCR. A consistent difference was noted between the two fibroblast sub-populations at early passage in respect of dipeptidyl peptidase IV (DPP IV) and aminopeptidase N (APN) expression. Early passage intralobular fibroblasts were positive for APN but negative for DPP IV, as seen in the intact tissue. However, with continued sub-culture they gradually began to express DPP IV, until at later passages they became indistinguishable from the interlobular fibroblasts, which were APN and DPP IV-positive at all stages in culture, as they are in intact tissue. Neutral endopeptidase (NEP/CALLA/CD10) is not expressed by normal adult breast fibroblasts but is found in the stroma associated with over 60% of breast cancers. It was up-regulated in vitro on both inter- and intralobular fibroblasts, with final levels that were significantly (< 14 times) higher on the former in all pairs of preparations from individual donors analysed. This difference persisted with continued passage, and levels of the ectoenzyme and its messenger RNA were further up-regulated by hydrocortisone in both populations. These results demonstrate that phenotypically distinct cultures of human mammary fibroblast sub-populations can be used to study the regulation of these stromal ectoenzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ectoenzyme regulation by phenotypically distinct fibroblast sub-populations isolated from the human mammary gland. 787 58

The immunocytochemical distribution of three cell surface peptidases was investigated in samples of developing infant breast ranging in age from newborn to 9.5 months. We have previously demonstrated that in the adult breast these enzymes identify subpopulations of epithelial cells and fibroblasts. We therefore wished to address two questions: (a) At what stage in breast development can fibroblast subpopulations be identified, and (b) Is the distribution of these peptidases related to cellular differentiation and morphogenesis? At the histological level there was a cuff of stromal cells closely associated with the developing ductular and lobular structures. At all stages of ductular and lobular development the fibroblasts in this layer were consistently negative for dipeptidyl peptidase IV (DPP IV) and clearly distinguished from the fibroblasts in the surrounding matrix, some of which expressed DPP IV in an age-dependent manner. Within the infant breast aminopeptidase N (APN) was localised to luminal epithelial cells and all fibroblasts, whilst neutral endopeptidase (NEP) was specifically localised to myoepithelial cells. These results are considered in relation to the role of stromal-epithelial interactions during morphogenesis and the proposed function of these enzymes.
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PMID:Immunolocalisation of cell surface peptidases in the developing human breast. 791 70

The longitudinal distribution of brush-border endopeptidase-24.11, endopeptidase-2, aminopeptidase W, angiotensin-converting enzyme (ACE), dipeptidyl peptidase IV (DPP IV), carboxypeptidase P, and aminopeptidase P in the rat intestine was determined. The jejunum has the highest activities of endopeptidase-24.11 and ACE while the ileum has the highest activities of aminopeptidase W and carboxypeptidase P, and the jejunoileal junction has the highest activity of aminopeptidase P. The jejunum and ileum have similar activities of DPP IV. The profiles of differential hydrolysis of neurotensin and acetylneurotensin (8-13) along the intestine agree with distribution of endopeptidase-24.11 and ACE, suggesting that amino acid sequences of peptides and the substrate specificity of enzymes will determine site-dependent hydrolysis. There is substantial similarity in the intestinal distribution of peptidases in the human, rat, and rabbit.
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PMID:Distribution of brush-border membrane peptidases along the rat intestine. 793 32

Distribution patterns of brush-border membrane dipeptidylpeptidase IV (DPP IV), endopeptidase-24.11, and angiotensin converting enzyme (ACE) activities along the intestine of the rat and rabbit were examined. ACE and endopeptidase-24.11 had a similar distribution profile in the intestine of the rat and rabbit, jejunum > duodenum approximately jejunoileal junction > ileum > caecum (rat) or ileocaecal junction (rabbit). DPP IV had a more uniform distribution pattern than ACE and endopeptidase-24.11. Its longitudinal distribution patterns in the intestine of the rat and rabbit were slightly different. In the rat intestine, DPP IV activity had the following rank order: ileum approximately jejunum > jejunoileal junction > duodenum > caecum. In the rabbit, DPP IV had similar activities from the jejunum to the ileocaecal junction whereas its duodenal activity was much lower. The results suggest that the distribution profiles of DPP IV, ACE, and endopeptidase-24.11 are similar in both species.
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PMID:Distribution of brush-border membrane peptidases along the intestine of rabbits and rats: implication for site-specific delivery of peptide drugs. 806 64

The distribution profiles of brush border membrane activities of endopeptidase-24.11, angiotensin converting enzyme (ACE), and dipeptidyl peptidase IV (DPP IV) along the rabbit intestine were examined. DPP IV had the lowest activity in the duodenum and much higher in other segments. In those segments, its activities were similar. As regards endopeptidase-24.11 and ACE, the jejunum had the highest activities, followed by the duodenum and the ileum. Activities of these two enzymes were lower in the distal intestine. The decline of ACE activity toward the distal end was more dramatic than that of endopeptidase-24.11 activity. The results suggest that, along the intestine, endopeptidase-24.11 and ACE have similar distribution profiles while DPP IV has a different distribution pattern.
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PMID:Distribution of brush-border membrane peptidases along the rabbit intestine: implication for oral delivery of peptide drugs. 809 14

Dipeptidyl peptidase IV (DPP IV, CD 26) is an integral membrane serine protease exhibiting a well characterized exopeptidase activity. The present study shows that DPP IV also possesses a novel gelatinase activity and therefore endopeptidase activity, which was directly demonstrated by gelatin zymography. Protease inhibitor profile analysis showed that the endo- and exopeptidase activities of DPP IV share a common active site. Substrate specificity was detected for denatured collagen types I, II, III and V suggesting that DPP IV might contribute to collagen trimming and metabolism. On the basis of these data we propose that DPP IV and the recently sequenced gelatinolytic seprase (FAPalpha) represent a new subfamily of gelatinolytic integral membrane serine proteases.
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PMID:Rat dipeptidyl peptidase IV (DPP IV) exhibits endopeptidase activity with specificity for denatured fibrillar collagens. 965 25


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