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

A series of prolineboronic acid (boroPro) containing dipeptides were synthesized and assayed for their ability to inhibit the serine protease dipeptidyl peptidase IV (DPPIV). Inhibitory activity, which requires the (R)-stereoisomer of boroPro in the P1 position, appears to tolerate a variety of L-amino acids in the P2 position. Substitution at the P2 position which is not tolerated include the D-amino acids, alpha,alpha-disubstituted amino acids, and glycine. Specificity against DPPII and proline specific endopeptidase is reported. A correlation between the ability to inhibit DPPIV in cell culture and in the human mixed lymphocyte reaction is demonstrated. A synthesis of prolineboronic acid is reported as well as conditions for generating the fully unprotected boronic acid dipeptides in either their cyclic or acyclic forms.
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PMID:Structure-activity relationships of boronic acid inhibitors of dipeptidyl peptidase IV. 1. Variation of the P2 position of Xaa-boroPro dipeptides. 864 68

Neuropeptide Y is one of the most abundant neuropeptides in the central and peripheral nervous systems and its sequence is highly conserved among species. A number of key physiological roles for NPY are now emerging, especially in the control of feeding and energy homeostasis. Other physiological actions of NPY are also reviewed. The metabolism of NPY has been examined by employing certain purified ectopeptidases and by using different membrane preparations. These approaches reveal that NPY is processed at its N-terminus by two proline-preferring aminopeptidases: aminopeptidase P and dipeptidyl peptidase IV. The action of the latter enzyme generates NPY (3-36) which has previously been shown to be a selective agonist at the Y2 class of NPY receptor. Thus, post-secretory processing of NPY can modify receptor selectivity. NPY is found to be resistant to the action of two other membrane aminopeptidases (N and W), and to the action of angiotensin converting enzyme. However, it is a substrate for endopeptidase-24.11 (K(m) = 15.4 microM) which can cleave the Tyr20-Tyr21 and Leu30-Ile31 bonds consistent with the known specificity of the enzyme. In striatal synaptic and renal brush border membranes, NEP is shown to be the major NPY hydrolysing activity but plays a lesser role in intestinal brush border membranes. Knowledge of the proteolytic processing of NPY should aid in the design of stable analogues of this neuropeptide.
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PMID:Metabolism and functions of neuropeptide Y. 889 76

In vivo, bicarbonate can affect proximal tubule intermediary metabolism, including gluconeogenesis, ammoniagenesis and maintenance of the mitochondrial substrate supply. In vitro, rabbit proximal tubule cells (RPTC) in primary culture revert from gluconeogenesis to glycolysis and their mitochondrial metabolism remains lower than in vivo. To determine whether the bicarbonate buffer system could have an effect on these deregulations, RPTC in primary culture grown in the absence of insulin and glucose in the culture medium were developed either with the standard sodium bicarbonate buffer with 5% CO2 or with a Hepes hydrogen ion buffer in the presence of 0.5% CO2. Duration of the bicarbonate-free cultures was increased until at least day 17 after seeding, compared with day 11 in bicarbonate-buffered cultures. As could be expected, succinate dehydrogenase activity remained stable as a function of time in bicarbonate-free cultures while an early marked decrease of this activity occurred from seeding in cultures developed in the presence of bicarbonate buffer. Compared to bicarbonate-buffered cells, higher phosphoenolpyruvate carboxykinase activity concomitant with lower intracellular lactate dehydrogenase activity was observed in cultures developed in the absence of bicarbonate, which is indicative of closer carbohydrate metabolism orientation to the in vivo situation for RPTC. Immunofluorescence staining of RPTC with monoclonal antibodies directed to neutral endopeptidase (NEP), and dipeptidyl-peptidase IV (DPP II) showed similar extensive labelling with DPP and NEP in both culture conditions. Confocal microscopy analysis of NEP subcellular distribution, showed exclusive targetting of NEP to the apical plasma membranes. In both models, cAMP production was stimulated by parathyroid hormone and unaffected by arginine vasopressin. In conclusion, bicarbonate withdrawal from the culture medium (without changing the pH of the medium) allows a marked improvement of mitochondrial capacity and carbohydrate metabolism pattern without any loss of differentiated properties.
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PMID:Effects of the medium HCO3-/CO2 buffer system on differentiation and intermediary metabolism properties of rabbit proximal tubule cells in primary culture. 897 88

Cholesteatoma is a destructive process involving an accumulation of desquamated keratin arising from squamous epithelium that pathologically has invaded the middle ear or mastoid process. The clinical hallmarks of cholesteatomas, namely invasion of healthy tissues, migration, unrestrained proliferation, aggressiveness, recidivism, and uncoordinated differentiation predict the existence of defects in the normal biology and biochemistry of the cellular constituents that compose a cholesteatoma, as well as in the cellular interactions between these cells, the surrounding normal tissue, and the host. In the current report, we analyzed 11 cholesteatomas and matched healthy tissue for altered expression in four different cell surface peptidases, aminopeptidase A, aminopeptidase N, dipeptidyl peptidase IV, and neutral endopeptidase. We suggest that peptidases may modulate cell growth and differentiation by inactivating stimulatory signals (or conversely, by activating inhibitory signals).
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PMID:Altered regulation of cell surface peptidases in human cholesteatoma. 901 59

Three cell surface peptidases have been shown to be present in the human endometrium. Aminopeptidase N and neutral endopeptidase are detected on the endometrial stromal cells and decidual cells, while dipeptidyl peptidase IV is detected on the endometrial glandular cells and surface epithelium. As these cell surface peptidases can degrade a variety of biologically-active peptides including cytokines and growth factors, they are considered to be involved in the local metabolism of these molecules. In addition, recent studies have indicated that they are involved in local immune responses, cell attachment, and cellular maturation/ differentiation of endometrial cells, and suggest an important role of these endometrial cell surface peptidases in implantation processes.
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PMID:Cell surface peptidases in human endometrium. 923 12

We report on the use of several proximal tubular cell (PTC) surface markets and corresponding antibodies in fluorescence-activated cell sorting (FACS), and their ability to identify and flow sort cells of defined proximal tubular origin (S1S2S3) or of defined proximal subsegmental origin (S1S2 only/S3 only). We tested monoclonal/polyclonal antibodies directed against five different surface peptidases [leucine aminopeptidase (LAP), neutral endopeptidase 24.11 (NEP), dipeptidyl peptidase IV (DPPIV), aminopeptidase A (APA) and gamma-glutamyl transferase (gamma-GT)], the S3 segment-specific marker intestinal type alkaline phosphatase (iAP) and an S1S2 marker (TN20-antigen), originally proposed as a surface marker for interstitial fibroblasts. Segmental (proximal tubular vs. distal tubular) and proximal subsegmental (S1S2 vs. S3) expression of all five surface peptidases and TN20 antigen were first assessed by comparing immunohistochemical staining on normal human kidney tissue with staining for well-known segment-specific differentiation markers (intestinal type alkaline phosphatase, Tamm-Horsfall protein) on adjacent sections. All five peptidases were found to be expressed to a certain degree in all subsegments (S1 S2 and S3) of the proximal nephron, whereas expression was never seen in the more distal parts of the nephron. Flow cytometry was performed on cells obtained following gradient purification of collagenase-digested human renal tissue. Labeling cells for expression of LAP, NEP or DPPIV resulted in high yields of specifically labeled PTC (S1S2S3 origin). Labeling with anti-LAP resulted in the clearest distinction between positive and negative cell subpopulations, and therefore LAP was considered the best PTC marker for use in FACS. iAP histochemical staining on sorted cells showed that flow sorting with monoclonal antibody (moAb) 250 (anti-intestinal type alkaline phosphatase) allowed sorting of S3 cells with > 90% purity. Likewise, moAb TN20 enabled us to obtain a highly purified S1S2 population as confirmed by the absence of iAP on sorted cells.
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PMID:Immunodissection of the human proximal nephron: flow sorting of S1S2S3, S1S2 and S3 proximal tubular cells. 926 97

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

The properties, distribution, and biological functions of several proteases from the plasma membrane of lymphoid cells are reviewed: dipeptidyl peptidase IV, neutral endopeptidase, aminopeptidases A and N, and a new protease of the family of adamalysins. these enzymes (designated as ectopeptidases) are integral membrane proteins whose molecules are mainly located extracellularly. Their functions involve proteolysis on the cell surface: the formation and inactivation of regulatory peptides and growth factors, as well as modification of cell surface proteins. The biological significance of a partial proteolysis of the plasma membrane proteins and the resulting soluble isoforms are discussed. An analysis of the data suggests that ectopeptidases from lymphoid cells are elements of the sensory system of the cell and are involved in the regulation of its physiological response to external factors and in the coordination of cell-cell interactions.
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PMID:[Plasma membrane proteinases from lymphoid cells and their biological functions]. 966 85

The regulatory mechanisms responsible for malignant transformation, tumor progression and metastasis in renal cell cancer (RCC) are still unclear, but there is some evidence that biologically active peptides might have regulatory effects on the behavior of this malignancy. Tumor cells can change local concentrations of active peptides by modulating their cell-surface enzymes. Using immunohistochemistry and enzyme-histochemistry, the expression of various membrane peptidases was examined in RCC and adjacent noninvaded renal parenchyma (n = 44). We describe the down-regulation of neutral endopeptidase 24.11 (NEP) protein expression in RCC of the clear cell/chromophilic type when compared with renal parenchyma, and show for the first time the lack of enzyme activity of NEP in RCC. The strongest expression could be found for dipeptidyl peptidase IV (DPIV) which is only decreased in RCC of the chromophobe cell type and is even present in oncocytoma. Aminopeptidase N (APN) and aminopeptidase A (APA) show attenuated expression in up to one third of clear cell/ chromophilic RCC. Chromophobe RCC and oncocytomas do not express APN, APA, NEP and gamma-glutamyltranspeptidase.
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PMID:Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer. 985 25

There is little data available regarding the extent of peptide metabolism encountered following inhalation to the lung. We have studied the activity of five ectopeptidases in primary rat alveolar epithelial cells, A549 cells and pulmonary macrophages. Peptidase activity was assayed in the plasma membrane fractions (PMF) of primary type II alveolar epithelial cells (ATII cells) after 2 days in culture and after 7 days in culture when they had formed monolayers of type I-like cells (ATI-like cells). Dipeptidyl peptidase IV (DPP) activity fell from 36.65 mU/mg protein to 16.29 mU/mg protein between day 2 and day 7 in culture, aminopeptidase N (AMN) activity increased from 16.16 mU/mg protein to 23.99 mU/mg protein, angiotensin-converting enzyme (ACE) activity was lost (4.29 mU/mg protein at day 2, not detected at day 7), and carboxypeptidase M (CPM) activity was acquired (not detected at day 2, 5.20 mU/mg protein at day 7). The profile of exopeptidase expression in A549 cells was similar to that of primary rat alveolar cells at day 7 in culture (DPP 24.24 mU/mg protein, AMN 47.74 mU/mg protein, CPM 4.28 mU/mg protein, ACE not detected). Macrophages expressed high levels of aminopeptidases (DPP 46.85 mU/mg protein, AMN 28.28 mU/mg protein) but carboxypeptidase activity was not detected. Low neutral endopeptidase 24.11 (NEP) activity was found in all cell types studied (0.96-2.41 mU/mg protein). The qualitative and quantitative changes in the peptidase activity of primary cultured rat alveolar cells between day 2 and day 7 in culture has implications for the use of alveolar cell monolayers as drug absorption models to investigate peptide absorption from the lung. Ectopeptidase activity in cultured alveolar cells can be used to infer the peptide-metabolising capacity of the surface of the alveolar epithelium. The aminopeptidase activity in particular, if representative of enzyme activity in vivo, would offer a significant metabolic barrier to systemic delivery of peptides via the lung.
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PMID:Temporal dependence of ectopeptidase expression in alveolar epithelial cell culture: implications for study of peptide absorption. 1037 Jan 93


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