Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PEPTIDASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,261 records · Page 70Linked to original sources
PubMed1994

Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen.

Massive proteinuria is induced in rats by administration of rabbit antibody to dipeptidyl peptidase IV (DPPIV, gp108), a glycoprotein present on glomerular cell membranes and in serum. This study was undertaken to know which antigen, glomerular or serum DPPIV, is responsible for forming immune complex in glomeruli and development of proteinuria. An i.p. injection of the antibody resulted in a rapid decrease of serum DPPIV and a gradual increase of rabbit IgG deposited along glomerular capillary wall for 4-8 h. Abnormal proteinuria appeared within 8 h, peaked on day 2 (> 200 mg/24 h) and then declined. An increase of urinary protein and glomerular deposition of IgG also occurred, when the antibody was injected into serum DPPIV-depleted rats that had received preinjection of anti-DPPIV antibody. These results suggest that proteinuria is induced by direct binding of anti-DPPIV antibody to the membrane antigen of glomerular cells.

Animals↗
PubMed1990

CD26 antigen is a surface dipeptidyl peptidase IV (DPPIV) as characterized by monoclonal antibodies clone TII-19-4-7 and 4EL1C7.

In this study we investigated the binding of three different monoclonal antibodies (MoAb), TII 19-4-7, 4EL1C7, and B1.19.2, which are clustered in CD26 to the ectoenzyme dipeptidyl peptidase IV (DPP IV) and to T lymphocytes. We found that all three MoAb bind to both unstimulated and mitogen-stimulated T lymphocytes. Further results indicated an inconsistency within the CD26-clustered MoAb: TII 19-4-7 and 4EL1C7, but not B1.19.2, recognized DPP IV on the surface o T lymphocytes and immobilized on solid-phase ELISA or Western blot. There was competition of binding to DPP IV between TII 19-4-7 and 4EL1C7. From these results we conclude that CD26 antigen is represented by the ectoenzyme DPP IV. TII 19-4-7 and 4EL1C7 recognize the same or partly identical epitopes on DPP IV, whereas B1.19.2 recognizes a different antigen. TII 19-4-7 and 4EL1C7, but not B1.19.2, should be clustered in CD26.

Antibodies, Monoclonal↗
PubMed1991

Development of monoclonal antibodies against different protein and carbohydrate epitopes of dipeptidyl peptidase IV from rat liver plasma membranes.

Dipeptidyl peptidase IV (DPP IV) is a serine exopeptidase expressed at high levels in rat kidney, liver and lung. We established eight monoclonal antibodies against partially purified DPP IV from rat liver plasma membranes. By means of a competitive dot blot assay with purified DPP IV, these antibodies were shown to recognize four different epitopes of the glycoprotein, designated A - D. The epitopes are located on the extracellular domain of DPP IV, as shown by papain digestion of liver plasma membranes. Treatment of DPP IV with neuraminidase and glycopeptide N-glycosidase F, as well as incubation of hepatocytes with the alpha-mannosidase I inhibitor deoxymannojirimycin, revealed that epitope A may be formed by a mannose-rich sugar chain and epitope D might represent a complex carbohydrate structure in the mature glycoprotein, while the epitopes B and C are formed by the protein moiety. Concanavalin A reduced the binding of monoclonal antibody to epitope A by 78%. Binding to epitope D was blocked by 73% with wheat germ lectin, and by more than 99% with sialic acid; epitopes B and C were unaffected by any of the lectins or sugars tested. The immunological cross-reactivity with DPP IV from Morris hepatoma 7777 was demonstrated with monoclonal antibodies against epitopes A-C. Epitope D was not recognized on hepatoma DPP IV. However, in addition to DPP IV, four hepatoma plasma membrane glycoproteins were precipitated by the monoclonal antibody against the epitope D, indicating that this epitope is not uniquely restricted to DPP IV.

Animals↗
PubMedDate not supplied

Dipeptidyl peptidase IV is down-regulated in rat hepatoma cells at the mRNA level.

Dipeptidyl peptidase IV (DPP-IV) is a cell surface ectopeptidase that has been implicated in cell-extracellular matrix interactions, lymphocyte growth and the regulation of biological peptides. Previous studies have shown that immunostaining for DPP-IV and DPP-IV enzyme levels is decreased in hepatoma cells and levels have been correlated with the ability of such cells to adhere in vitro. The aim of this paper was to measure DPP-IV enzyme levels in rat hepatoma cells and to examine whether changes were associated with alterations at the mRNA level. The results indicate a greater than 90% reduction in DPP-IV enzyme levels in two rat hepatoma cell lines, HTC and H35, compared with rat hepatocytes. Enzyme levels of the control enzyme leucine aminopeptidase (LAP) were not decreased. mRNA studies indicated that these changes were associated with similar reductions in rat DPP-IV mRNA. It is concluded that DPP-IV is markedly reduced at the protein, enzyme and mRNA levels in rat hepatoma cells. The significance of these changes is unclear but may lead to decreased extracellular matrix interactions by such cells.

Animals↗
PubMed1992

Cathepsin B/L-, elastase-, tryptase-, trypsin- and dipeptidyl peptidase IV-like activities in gingival crevicular fluid. A comparison of levels before and after basic periodontal treatment of chronic periodontitis patients.

20 chronic periodontitis patients were given a full periodontal examination, including measurements of probing depth, clinical attachment loss, gingival index, bleeding index and plaque index. At a second visit, gingival crevicular fluid (GCF) was collected from the deepest accessible probing site of each tooth. The patients then received scaling, root planing and other appropriate nonsurgical treatment. GCF was collected from the same sites as sampled pretreatment and clinical parameters were measured again. Cathepsin B/L-, elastase-, tryptase-, trypsin-, and dipeptidyl peptidase IV-like activities in GCF samples were determined by fluorimetric assay with peptidyl derivatives of 7-amino-4-trifluoromethyl coumarin. Following treatment, there were reductions in all clinical parameters and all protease activities. Most were statistically significant both on a patient level using average patient values and on a site level using either individual patient or pooled patient data. As in previous pre-treatment comparisons, post-treatment protease levels correlated positively and significantly with the corresponding clinical parameters at patient and site levels. The reductions and correlations were more marked for total enzyme activities than concentrations. GCF protease levels appear to reflect the clinical status of periodontal lesions and may thus be of value in monitoring disease activity.

Adult↗
PubMed1989

Detection of cathepsin B- and L-, elastase-, tryptase-, trypsin-, and dipeptidyl peptidase IV-like activities in crevicular fluid from gingivitis and periodontitis patients with peptidyl derivatives of 7-amino-4-trifluoromethyl coumarin.

Crevicular fluid samples were collected from 20 gingivitis and periodontitis patients using filter paper strips; these were then eluted into buffer. Portions of each sample were combined and the activities of this pooled eluate against different peptidyl derivatives of 7-amino-4-trifluoromethyl coumarin (AFC) were examined with respect to their pH profiles and effector responses. Ca-thepsin B- and L-like activity was detected with Bz-Val-Lys-Lys-Arg-AFC; elastase-like activity with MeOSuc-Ala-Ala-Pro-Val-AFC; tryptase-like activity with Z-Ala-Ala-Lys-AFC; trypsin-like activity with Z-Gly-Gly-Arg-AFC; and dipeptidyl peptidase (DPP) IV-like activity with Ala-Pro-AFC. The selectivity and sensitivity of these assays were improved by choice of appropriate conditions. The cathepsin B- and L-, elastase-, tryptase-, and trypsin-like activities all had properties consistent with those from host sources, whilst partial inactivation of the DPP IV-like activity by heat treatment (60 degrees C for 30 min) suggested that it may have represented a mixture of human and Bacteroides gingivalis enzymes. Individual patient eluates showed wide variations in enzyme concentrations, but generally elastase-like activity was by far the highest. The sensitivity of the assays with AFC-linked substrates was such that it should prove possible to measure all five different types of activity in crevicular fluid samples from local periodontal disease sites.

Amino Acid Sequence↗
PubMed1995

Correlation between gingival crevicular fluid dipeptidyl peptidase II and IV activity and periodontal attachment loss. A 2-year longitudinal study in chronic periodontitis patients.

OBJECTIVE: The aim of this study is to determine whether gingival crevicular fluid (GCF) dipeptidyl peptidase (DPP) II or IV levels, total activity (TA) and concentration (EC), predict progressive attachment loss (AL). SUBJECTS AND METHODS: Seventy five patients with moderate periodontitis were recruited. GCF was first collected from 16 molar and premolar mesiobuccal sites and then probing attachment level (PAL) and probing pocket depth (PPD) were measured with an electronic probe. Finally, gingival index, gingival bleeding and plaque indices were scored. Patients were given basic periodontal treatment prior to baseline after which the above procedures were repeated. Patients were seen 3 monthly for 2 years and the procedures were repeated. Carefully localised radiographs were taken of the test teeth annually. RESULTS: One hundred and twenty AL sites, 88 rapid AL (RAL) and 32 gradual AL (GrAL), in 48 patients were detected. DPP II and IV levels (TA and EC) at RAL sites were significantly higher (P < or = 0.0001) than paired control sites at the attachment loss time (ALT) and prediction time (PT). Mean levels over the study period of both proteases (TA and EC) at GrAL sites were significantly higher (P < or = 0.0001) than other paired control sites. The GCF levels of DPP IV were always slightly higher than those of DPP II. Critical values (CV) of 5 microU per 30 s (TA) and 25 microU microL(-1) (EC) for both proteases showed high sensitivity and specificity values for TA and EC and these were the same at both ALT and PT. The positive predictive values were slightly higher for DPP II. Mean site DPP II and IV levels (TA and EC) in intra-patient comparisons were significantly higher (P < or = 0.0001) at RAL and GrAL sites than non-attachment loss (NAL) sites in AL patients and mean patient levels were significantly higher (P < or = 0.0001) in AL patients than NAL patients in inter-patient comparisons. CONCLUSIONS: These results indicate that both GCF DPP II and IV may be predictors of periodontal attachment loss.

Adult↗
PubMed2006

7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one is a novel competitive and selective inhibitor of dipeptidyl peptidase IV with an antihyperglycemic activity.

7-But-2-ynyl-9-(6-methoxy-pyridin-3-yl)-6-piperazin-1-yl-7,9-dihydro-purin-8-one (ER-319711) is a novel dipeptidyl peptidase (DPP)-IV inhibitor discovered in our laboratories. In this study, we have characterized this DPP-IV inhibitor in vitro and in vivo as an antidiabetic agent. The trifluoroacetate salt form of ER-319711, ER-319711-15, inhibited human DPP-IV with an IC(50) value of 0.089 microM, whereas its IC(50) values toward human DPP8 and DPP9 were >100 microM. Inhibition kinetic pattern analysis indicated that ER-319711-15 inhibited DPP-IV in a competitive manner. ER-319711-15 (1 mg/kg) reduced glucose excursion in an oral glucose tolerance test (OGTT) using Zucker fa/fa rats, with significant increases in plasma insulin and active glucagon-like peptide-1 levels. In an OGTT using mice fed a high-fat diet in which ER-319711-15 (0.1-10 mg/kg) was orally administered at 0 h, and glucose was loaded at 0 and 5 h, this compound improved glucose tolerance dose dependently at both 0- and 5-h glucose loading. Next, we compared efficacy of ER-319711-15, E3024, a competitive DPP-IV inhibitor having an imidazopyridazinone structure, or vildagliptin, a slow-binding and long-acting DPP-IV inhibitor, at the same dose, 10 mg/kg, in the same procedures. At the first glucose challenge, all compounds lowered area under the curve (AUC) values of delta blood glucose between 0 and 2 h significantly to the same degree. At the second glucose load, the AUC values between 5 and 7 h were significantly decreased by ER-319711-15 and vildagliptin, but not by E3024. Therefore, ER-319711 might be a potent, competitive, and selective DPP-IV inhibitor with an antihyperglycemic activity.

Adamantane↗
PubMedDate not supplied

Detection of dipeptidyl peptidase IV in glioma C6 and neuroblastoma SK-N-SH cell lines.

The dipeptidyl peptidase IV (DPP-IV) activity of the rat glioma cell line C6 and the human neuroblastoma cell line SK-N-SH was investigated. DPP-IV fluorescent substrate was cleaved by both cell lines. The pH reaction optimum determined was typical for DPP-IV described in other cell models. The reaction was inhibited by specific inhibitors diprotins A and B. Enzyme activity was localized, both on the cell surface and intracellularly. Most of the DPP-IV activity was membrane bound. However, soluble intra-cellular activity was found in both cell lines. Secreted activity was not detected in either cell line. In the C6 line, but not in the SK-N-SH line, we demonstrated depression of the ratio of cell surface to total cell DPP-IV activity at higher cell densities, indicating possible enzyme redistribution during cell growth in culture. Identification of DPP-IV activity is the first step in our study of the role of DPP-IV in the neural system.

Animals↗
PubMed1991

Dipeptidyl peptidase IV expression in rat jejunal crypt-villus axis is controlled at mRNA level.

The expression of dipeptidyl peptidase IV (DPP IV), an intestinal brush-border hydrolase, has been studied in the rat jejunum crypt-villus axis. DPP IV enzyme activity is lower in crypt cells than in villus cells. Indirect immunofluorescence studies, using a polyclonal antibody raised against purified DPP IV, show a gradient of immunoreactivity from the crypts to the villi that was quantified using confocal laser scanning microscopy. Accordingly, Western blot analysis demonstrates that the steady-state amount of DPP IV is much lower in crypt cells than in villus cells. Northern blot analysis was performed using our cDNA probe for human DPP IV that presents more than 94% homology with rat DPP IV cDNA. Results clearly show that there is approximately seven times less DPP IV mRNA in crypt cells than in villus cells. We conclude that the differentiation-dependent expression of DPP IV in rat jejunum is primarily controlled at the mRNA level.

Animals↗
PubMed2004

PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism.

The amino boronic dipeptide, PT-100 (Val-boro-Pro), a dipeptidyl peptidase (DPP) inhibitor, has been shown to up-regulate gene expression of certain cytokines in hematopoietic tissue via a high-affinity interaction, which appears to involve fibroblast activation protein. Because fibroblast activation protein is also expressed in stroma of lymphoid tissue and tumors, the effect of PT-100 on tumor growth was studied in mice in vivo. PT-100 has no direct cytotoxic effect on tumors in vitro. Oral administration of PT-100 to mice slowed growth of syngeneic tumors derived from fibrosarcoma, lymphoma, melanoma, and mastocytoma cell lines. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 caused regression and rejection of tumors. The antitumor effect appeared to involve tumor-specific CTL and protective immunological memory. PT-100 treatment of WEHI 164-inoculated mice increased mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells. The role of innate activity was further implicated by observation of significant, although reduced, inhibition of WEHI 164 and A20/2J tumors in immunodeficient mice. PT-100 also demonstrated ability to augment antitumor activity of rituximab and trastuzumab in xenograft models of human CD20(+) B-cell lymphoma and HER-2(+) colon carcinoma where antibody-dependent cytotoxicity can be mediated by innate effector cells responsive to the cytokines and chemokines up-regulated by PT-100. Although CD26/DPP-IV is a potential target for PT-100 in the immune system, it appeared not to be involved because antitumor activity and stimulation of cytokine and chemokine production was undiminished in CD26(-/-) mice.

Administration, Oral↗
PubMed1989

Dipeptidyl amino peptidase IV cytochemistry in circulating lymphocytes from HIV-I-seropositive subjects.

In order to assess whether changes in the relative proportions of cells pertaining to different T-lymphocyte subsets correlate with dipeptidyl amino peptidase IV (DAP IV) activity, the enzyme was cytochemically investigated in circulating lymphocytes from 20 HIV-I-seropositive drug addicts. Although on the average, a significant reduction of lymphocyte DAP IV activity was found in comparison with healthy control subjects, wide variations between individual cases were observed, and no obvious relationship emerged between DAP IV staining on one hand, immunocytological findings and Walter Reed staging on the other. Therefore, in view of the preliminary results reported, the variations of lymphocyte DAP IV activity in the course of HIV I infection seem to deserve further investigation, in order to clarify both the biological significance of this reaction and its possible clinical relevance.

Adolescent↗
PubMed1993

Dipeptidyl peptidase IV is sorted to the secretory granules in pancreatic islet A-cells.

Dipeptidyl peptidase IV (DP IV:EC 3.4.14.5) was localized in endocrine cells of pig pancreas by immunohistochemical and enzyme histochemical methods. Immunolight microscopy with both monoclonal and polyclonal antibodies demonstrated DP IV immunoreactivity in cells located in the peripheral part of the islets of Langerhans. The antigen is enzymatically active, as shown by enzyme histochemical analysis with a synthetic DP IV substrate. By immunoelectron microscopy (immunogold labeling), the labeling of DP IV in the islets was associated with the secretory granules of the A-cells, as identified by double labeling using a monoclonal glucagon antibody as the second primary antibody. These results show that DP IV is sorted to secretory granules in the pig pancreatic islet A-cells. Furthermore, this secretory granule enzyme, as opposed to intestinal brush border DP IV, is suggested to be a soluble protein, since the gold particles appear all over the granules and are not specifically associated with the granule membrane.

Animals↗
PubMed1990

Quantitative immunogold localization of dipeptidyl peptidase IV (DPP IV) in rat liver cells.

We investigated ultrastructural localization of dipeptidyl peptidase IV (DPP IV) [EC3.4.14 5] in rat liver cells quantitatively by post embedding protein A-gold technique. In the hepatocyte, DPP IV was mainly localized on the bile canalicular surface and the lysosomal membranes, but were scarcely detectable on the sinusoid-lateral surface. A small number of DPP IV was also detected in the trans region of the Golgi apparatus, suggesting that this part may play important roles in intracellular transport or recycling of this enzyme. In the endothelial cell, DPP IV existed on the whole surface of the plasma membrane and the lysosomes. In the Kupffer cell DPP IV was mainly localized in lysosomes and a few were detected on the plasma membrane.

Animals↗
PubMed2006

Tripeptidyl-peptidase I in health and disease.

The lysosomal lumen contains numerous acidic hydrolases involved in the degradation of carbohydrates, lipids, proteins, and nucleic acids, which are basic cell components that turn over continuously within the cell and/or are ingested from outside of the cell. Deficiency in almost any of these hydrolases causes accumulation of the undigested material in secondary lysosomes, which manifests itself as a form of lysosomal storage disorder (LSD). Mutations in tripeptidyl-peptidase I (TPP I) underlie the classic late-infantile form of neuronal ceroid lipofuscinoses (CLN2), the most common neurodegenerative disorders of childhood. TPP I is an aminopeptidase with minor endopeptidase activity and Ser475 serving as an active-site nucleophile. The enzyme is synthesized as a highly glycosylated precursor transported by mannose-6-phosphate receptors to lysosomes, where it undergoes proteolytic maturation. This review summarizes recent progress in understanding of TPP I biology and molecular pathology of the CLN2 disease process, including distribution of the enzyme, its biosynthesis, glycosylation, transport and activation, as well as catalytic mechanisms and their potential implications for pathogenesis and treatment of the underlying disease. Promising data from gene and stem cell therapy in laboratory animals raise hope that CLN2 will be the first neurodegenerative LSD for which causative treatment will become available for humans.

Aminopeptidases↗
PubMed1990

Purification and properties of dipeptidyl peptidase IV from human urine.

Dipeptidyl peptidase IV (DPP-IV) (EC 3.4.14.5) has been purified from normal human urine using immunoaffinity chromatography. The purified enzyme was homogeneous as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The molecular mass of urinary DPP-IV was estimated to be 280 kDa by gel filtration. The Km value for the hydrolysis of (Gly-L-Pro)-4-methylcoumaryl-7-amide tosylate was calculated to be 1.25 +/- 0.25 X 10(-4) M; the pH optimum and pI were 8.7 and 6.5, respectively. These properties were the same as those of renal DPP-IV. Both renal and this urinary DPP-IV were inhibited by diisopropylfluorophosphate and activated by phospholipid. From these results we suppose that urinary DPP-IV may be derived from the kidney rather than from the blood

Adult↗
PubMed1992

Prolyl endopeptidase and dipeptidyl peptidase IV are distantly related members of the same family of serine proteases.

Prolyl endopeptidase and dipeptidyl peptidase IV are serine proteases which cleave the peptide bonds at the carboxy group of proline residues. They do not show amino acid sequence homology with the known serine enzymes, but a possible relationship between them has not yet been examined. We have compared the amino acid sequences, and this revealed a distant evolutionary relationship between the two enzymes. Conserved segments were found mainly in the C-terminal region which also contained the catalytic residues. It is concluded that the C-terminal region is a protease domain which is attached to some noncatalytic structures.

Amino Acid Sequence↗