Dipeptidyl peptidase IV (DPP IV/CD26) is a cell-surface plasminogen receptor

Dipeptidyl peptidase IV (DPP IV) is a cell surface glycoprotein which has been implicated in hepatocyte-extracellular matrix interactions [Hixson, DeLourdes, Ponce, Allison & Walborg (1984) Exp. Cell Res. 152, 402-414; Walborg, Tsuchida, Weeden, Thomas, Barrick, McEntire, Allison & Hixson (1985) Exp. Cell Res. 158, 509-518; Hanski, Huhle & Reutter (1985) Biol. Chem. Hoppe-Seyler 366, 1169-1176]. However, its proteolytic substrate(s) and/or binding protein(s) which mediate this influence have not been conclusively identified. Nitrocellulose binding assays using 125I-labelled DPP IV that was purified to homogeneity from rat hepatocytes revealed a direct interaction of DPP IV with fibronectin. Although fibronectin could mediate an indirect binding of DPP IV to collagen, no evidence was found for a direct binding of DPP IV to native or denatured Type I collagen. Fibronectin appeared to bind DPP IV at a site distinct from its exopeptidase substrate recognition site since protease inhibitors such as competitive peptide substrates and phenylmethanesulphonyl fluoride enhanced binding, possibly as a result of an altered conformation of DPP IV. To determine if fibronectin binding to DPP IV is involved in the interaction of fibronectin with the hepatocyte surface, the effect of various DPP IV inhibitors on 125I-fibronectin binding to isolated hepatocytes in suspension was examined. Kinetic studies revealed that inhibitors of DPP IV which enhanced fibronectin binding in vitro accelerated the initial binding of fibronectin to the cell surface where it was subsequently cross-linked (presumably by tissue transglutaminase) to as yet undefined components. Immunolocalization of fibronectin and DPP IV in normal rat liver sections showed that both proteins were present along the hepatocyte sinusoidal membrane. These observations, coupled with previous results showing that DPP IV is tightly bound to biomatrix isolated from rat liver (Hixson et al., 1984; Walborg et al., 1985), suggest that DPP IV binding to fibronectin may play a role in interactions of hepatocytes with extracellular matrix in vivo and possibly in matrix assembly.

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

Biochemistry and Cell Biology ◽

10.1139/o95-013 ◽

1995 ◽

Vol 73 (1-2) ◽

pp. 113-115 ◽

Cited By ~ 4

Author(s):

Aleksi Sedo ◽

Roberto P. Revoltella

Keyword(s):

Cell Surface ◽

Cell Line ◽

Cell Lines ◽

Neuroblastoma Cell ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Human Neuroblastoma Cell ◽

Fluorescent Substrate ◽

Human Neuroblastoma ◽

Dpp Iv

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.Key words: dipeptidyl peptidase IV, glioma, neuroblastoma.

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Automatic Recognition of Muscle-Invasive T-Lymphocytes Expressing Dipeptidyl-Peptidase IV (CD26) and Analysis of the Associated Cell Surface Phenotypes

Journal of Theoretical Medicine ◽

10.1080/10273660290015189 ◽

2002 ◽

Vol 4 (1) ◽

pp. 67-74 ◽

Cited By ~ 9

Author(s):

W. Schubert ◽

M. Friedenberger ◽

R. Haars ◽

M. Bode ◽

L. Philipsen ◽

...

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Cell Surface ◽

Detection System ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Cell Detection ◽

Surface Receptors ◽

Dpp Iv ◽

Muscle Invasive

A neural cell detection system (NCDS) for the automatic quantitation of fluorescent lymphocytes in tissue sections was used to analyze CD26 expression in muscle-invasive T-cells. CD26 is a cell surface dipeptidyl-peptidase IV (DPP IV) involved in co-stimulatory activation of T-cells and also in adhesive events. The NCDS system acquires visual knowledge from a set of training cell image patches selected by a user. The trained system evaluates an image in 2 min calculating (i) the number, (ii) the positions and (iii) the phenotypes of the fluorescent cells. In the present study we have used the NCDS to identity DPP IV (CD26) expressing invasive lymphocytes in sarcoid myopathy and to analyze the associated cell surface phenotypes. We find highly unusual phenotypes characterized by differential combination of seven cell surface receptors usually involved in co-stimulatory events in T-lymphocytes. The data support a differential adhesive rather than a co-stimulatory role of CD26 in muscle-invasive cells. The adaptability of the NCDS algorithm to diverse types of cells should enable us to approach any invasion process, including invasion of malignant cells.

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Modulation of substance P signaling by dipeptidyl peptidase-IV enzymatic activity in human glioma cell lines

Physiological Research ◽

10.33549/physiolres.931231 ◽

2008 ◽

pp. 443-449

Author(s):

P Bušek ◽

J Stremeňová ◽

E Křepela ◽

A Šedo

Keyword(s):

Substance P ◽

Cell Surface ◽

Intracellular Calcium ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Biologically Active ◽

Wild Type ◽

Surface Receptors ◽

Dpp Iv ◽

Stromal Cell Derived Factor

Dipeptidyl peptidase-IV (DPP-IV, CD26) is a serine protease almost ubiquitously expressed on cell surface and present in body fluids. DPP-IV has been suggested to proteolytically modify a number of biologically active peptides including substance P (SP) and the chemokine stromal cell derived factor-1α (SDF-1α, CXCL12). SP and SDF-1α have been implicated in the regulation of multiple biological processes and also induce responses that may be relevant for glioma progression. Both SP and SDF-1α are signaling through cell surface receptors and use intracellular calcium as a second messenger. The effect of DPP-IV on intracellular calcium mobilization mediated by SP and SDF-1α was monitored in suspension of wild type U373 and DPP-IV transfected U373DPPIV glioma cells using indicator FURA-2. Nanomolar concentrations of SP triggered a transient dose dependent increase in intracellular calcium rendering the cells refractory to repeated stimulation, while SDF-1α had no measurable effect. SP signaling in DPP-IV overexpressing U373DPPIV cells was not substantially different from that in wild type cells. However, preincubation of SP with the DPP-IV overexpressing cells lead to the loss of its signaling potential, which could be prevented with DPP-IV inhibitors. Taken together, DPP-IV may proteolytically inactivate local mediators involved in gliomagenesis.

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Reduced Cell Surface Expression of a Mutated Dipeptidyl Peptidase IV (DPP IV/CD26) Correlates with the Generation of a β Strand in Its C-Terminal Domain

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1996.0828 ◽

1996 ◽

Vol 222 (3) ◽

pp. 833-838 ◽

Cited By ~ 4

Author(s):

Frédéric David ◽

Laurent Baricault ◽

Catherine Sapin ◽

Xavier Gallet ◽

Didier Marguet ◽

...

Keyword(s):

Cell Surface ◽

Surface Expression ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Cell Surface Expression ◽

Terminal Domain ◽

Dpp Iv

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Dipeptidyl Peptidase IV Inhibitors for Nonalcoholic Fatty Liver Disease – Systematic Review and Metanalysis

Current Diabetes Reviews ◽

10.2174/1573399816999201110195634 ◽

2020 ◽

Vol 16 ◽

Author(s):

Lucas Ribeiro dos Santos ◽

Marcio Luis Duarte ◽

Maria Stella Peccin ◽

Antônio Ricardo de Toledo Gagliardi ◽

Tamara Melnik

Keyword(s):

Hepatic Steatosis ◽

Grey Literature ◽

Specific Treatment ◽

Reducing Power ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase Iv ◽

Cochrane Library ◽

Vast Number ◽

Dpp Iv ◽

Dipeptidyl Peptidase Iv Inhibitors

Introduction:: Hepatic steatosis is a frequent condition, that afflicts, especially, obese and insulin resistant patients; diagnosis is made, usually, through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective:: To determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP-IV) in the treatment of NAFLD. Methods:: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results:: 7 studies were used for metanalysis, for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 [95% CI 35.23 to 13.57] at 3 months and MD -9.27 [95% CI 10.92 to -7.62] at 6 months of intervention, as well as reduction of hepatic steatosis via MRI of SMD 0.10 [95% CI 0.31 to 0.50]; the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion:: Because of the poor overall quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.

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