Increase Of DPP Research Articles

Response of Southern Ocean phytoplankton and bacterioplankton production to short‐term experimental warming

We examined the potential response of Southern Ocean pelagic ecosystems to warming through changes in total primary production (particulate plus dissolved = PPP + DPP) and bacterial production (BP), determined simultaneously at ambient temperature (−1.4 to 0.4°C) and at 2°C in eight experiments performed near the Antarctic Peninsula in late spring 2002. Short (<6 h) time course experiments of radiocarbon uptake and photosynthesis‐irradiance relationships consistently showed that a significant amount of photosynthate appeared as dissolved substances, with a mean 35% extracellular release (PER). Whereas PPP remained virtually unchanged (0.7 mg C m−3 h−1), DPP increased significantly at 2°C from 0.5 to 0.9 mg C m−3 h−1. The corresponding increase in PER (54% on average) was significantly and positively correlated with the temperature difference among treatments, suggesting that an increase in DPP could be expected with a temperature rise in the Southern Ocean. BP, estimated via [3H]leucine incorporation, tended to increase at 2°C only at low absolute values, and this increment was inversely related to PPP. However, our results show that the estimated bacterial carbon demand (BCD) was generally well below concurrent DPP at both treatments (mean BCD:DPP ratios of 0.60 and 0.27 at ambient temperature and 2°C, respectively), indicating that temperature‐related extra inputs of organic substrates were not fully and immediately processed by bacteria. To the extent that these results reflect general ecophysiological trends, warming of Southern Ocean surface waters could produce changes in plankton‐mediated biogeochemical processes leading to a greater importance of dissolved organic matter fluxes.

Eating disorders: a role for dipeptidyl peptidase IV in nutritional control

Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, has been postulated to modulate nutrition control by modification or inactivation of peptide hormones operating in the enteroinsular axis. We hypothesized that changes of DPP IV activity in serum are related to the nutrition status of patients with eating disorders. Serum DPP IV activity was measured in 52 patients (28 with anorexia nervosa and 24 with bulimia nervosa) in four consecutive weekly analyses. Simultaneously, the number of CD26 (DPP IV)-positive peripheral blood lymphocytes was counted. The same analyses were carried out in 28 healthy female volunteers. In week 1 and throughout the observation period, DPP IV activity in the sera of patients with anorexia nervosa and, to a lesser extent, those with bulimia nervosa was elevated in comparison to that of healthy controls (week 1: means = 92.8 U/L for anorexia-nervosa patients and 89.3 U/L for bulimia-nervosa patients versus 74.7 U/L for healthy control subjects, P = 0.014; weeks 1–4: 91.8 U/L for anorexia-nervosa patients and 86.2 U/L for bulimia-nervosa patients versus 77.6 U/L for healthy controls, P < 0.001). We assume that the increase in DPP IV serum activity will increase the turnover of distinct peptide hormones with known effects on nutrition control and susceptibility to degradation by DPP IV. The potential impact of an increase in DPP IV activity in serum on satiety and nutrition control contributes to previously reported implications for immune function.

INVOLVEMENT OF CD26/DPP IV IN ALLOANTIGEN-INDUCED HUMORAL IMMUNE RESPONSES IN ALLOGRAFT RECIPIENTS

510 CD26, a major lymphocyte costimulatory molecule, binds to extracellular matrix proteins, HIV Tat-1 protein, adenosine deaminase, and CD45. In vitro costimulatory efficacy and in vivo immunocompetence have been linked to the enzymatic activity of CD26 (dipeptidyl peptidase IV; DPP IV). Several cytokines and growth factors are susceptible to cleavage by this serine-type protease. Previously, we have documented that specific targeting of DPP IV enzymatic activity affected proliferative, cytotoxic and humoral immune responses in allograft recipients. This resulted in the abrogation of acute and accelerated rejection of cardiac allografts in otherwise untreated and sensitized rats, respectively. The aim of this study was to further investigate the involvement of CD26/DPP IV in allospecific humoral immunity in transplant recipients. Treatment of LEW rat recipients of LBNF1 cardiac allografts with a low molecular weight inhibitor of DPP IV enzymatic activity (pro-pro-diphenyl phosphonate; 15 mg/rat sc. at days 0, 3 and 6 post-transplant) abrogated circulating donor-specific IgM allo-Ab responses, and markedly decreased IgG allo-Ab titers in the serum (n=10). Concomitant analysis of total immunoglobulin did not reveal significant differences in IgM and IgG allo-Ab levels between treated and untreated hosts. Assessment of IgG subclasses(IgG1, IgG2a, and IgG2b) showed a significant (p<0.05) drop in secretion of IgG2b allo-Ab in treated animals at 14 and 21 days post-transplant(n=4/7), as compared to untreated rejecting controls. Post-transplant treatment of LEW rats with OX-61 mAb, directed against rat CD26, not only caused a strong increase in DPP IV serum activity, but it also resulted in augmented and enduring circulating IgM allo-Ab titers (n=2). The OX-61-mediated effects were reflected in an acute-type allograft rejection pattern, comparable with untreated recipients. In conclusion, inhibition of DPP IV enzymatic activity interferes with the initiating step of the humoral response to a protein Ag following organ transplantation. Selective impairment of allospecific Ab secretion, while non-specific immunoglobulins are being generated, may suggest a CD26/DPP IV-mediated effect during early T cell-dependent B cell responses. Modulation of CD26 catalytic activity may influence the physiological maturation process of specific Abs. Hence, our findings suggest a central role of CD26/DPP IV in allo-Ag mediated humoral immune pathways in transplant recipients.

X-ray diffraction and calorimetric study of N-lignoceryl sphingomyelin membranes

Differential scanning calorimetry and x-ray diffraction have been used to investigate hydrated multibilayers of N-lignoceryl sphingomyelin (C24:0-SM) in the hydration range 0-75 wt % H2O. Anhydrous C24:0-SM exhibits a single endothermic transition at 81.3 degrees C (delta H = 3.6 kcal/mol). At low hydration (12.1 wt % H2O), three different endothermic transitions are observed: low-temperature transition (T1) at 39.4 degrees C (transition enthalpy (delta H1) = 2.8 kcal/mol), intermediate-temperature transition (T2) at 45.5 degrees C, and high-temperature transition (T3) at 51.3 degrees C (combined transition enthalpy (delta H2 + 3) = 5.03 kcal/mol). On increasing hydration, all three transition temperatures of C24:0-SM decrease slightly to reach limiting values of 36.7 degrees C (T1), 44.4 degrees C (T2), and 48.4 degrees C (T3) at approximately 20 wt % H2O. At 22 degrees C (below T1), x-ray diffraction of C24:0-SM at different hydration levels shows two wide-angle reflections, a sharp one at 1/4.2 A-1 and a more diffuse one at 1/4.0 A-1 together with lamellar reflections corresponding to bilayer periodicities increasing from d = 65.4 A to a limiting value of 71.1 A. Electron density profiles show a constant bilayer thickness dp-p approximately 50 A. In contrast, at 40 degrees C (between T1 and T2) a single sharp wide-angle reflection at approximately 1/4.2 A-1 is observed. The lamellar reflections correspond to a larger bilayer periodicity (increasing from d = 69.3-80.2 A) and there is some increase in dp-p (52-56 A) with hydration. These structural parameters,together with calculated lipid thickness and molecular area considerations, suggest that the low temperature endotherm(T1) of hydrated C24:0-SM corresponds to a transition from a tilted, gel state (Gel I) with partially interdigitated chains to an untilted, or less tilted, gel state (Gel 11). At 600C (above T3), the usual liquid-crystalline La bilayer structure (d = 59.5-66.3A; dp p -46 A) is present at all hydrations. Comparison with the behavior of C18:0-SM indicates that the in equivalence of length of the sphingosine (C18) and lignoceryl (C24) chains results in a more complex gel phase polymorphism for the sphingosine (C18) and lignoceryl (C24) chains results in a more complex gel phase polymorphism for C24:0-SM.

Biochemical properties of dipeptidyl peptidase IV in liver and hepatoma plasma membranes

In the present investigation we compared the glycoprotein DPP IV from rat liver and Morris hepatoma 7777 by means of biochemical and immunological methods. For that purpose nine monoclonal anti-DPP IV-antibodies recognizing four different epitopes and a monospecific anti-DPP IV-antiserum were applied. In the homogenates of both tissues a plasma membrane-bound and a soluble form were detected. The immunological cross-reactivity of both forms was demonstrated with the antiserum and the monoclonal antibodies against the epitopes A, B and C while epitope D was restricted to liver plasma membrane. Differences of the distinct DPP IV forms were exhibited in the molecular weights, isoelectric points and peptide maps. In the hepatoma homogenate only 10% of DPP IV activity was found compared to normal liver but the ratio of soluble to membrane-bound form is higher in the hepatoma than in the liver. The fractionation of the homogenates into different cell components revealed for the liver a continuous increase of DPP IV activity from the endoplasmic reticulum fractions to the Golgi apparatus and finally to the plasma membranes. By contrast, in hepatoma the flow from the Golgi apparatus to plasma membrane was greatly reduced. The loss of DPP IV from the surface of cultured hepatoma cells was concomitant with a decrease of cell-substratum adhesion. DPP IV was found to be inserted into the liver plasma membrane by two different mechanisms, a phospholipase C-sensitive and a papain-sensitive one. In the hepatoma the phospholipase C-sensitive anchorage was not expressed. Besides liver and hepatoma the distribution of DPP IV was characterized in various rat organs by enzyme activity, histochemistry and immunohistochemistry with the anti-DPP IV-antibodies.

Evidence for sequential deployment of secretory enzymes during the normal acrosome reaction of guinea pig sperm in vitro.

Experiments were conducted to determine if acrosomal enzymes are released simultaneously or in sequence during the normal acrosome reaction. Epididymal guinea pig sperm were incubated in a chemically defined, calcium-containing medium which supports normal acrosome reactions within 4-5 hours at 37 degrees C. The sperm suspensions were monitored for motility, normal acrosome reactions, and false acrosome reactions during in vitro incubation. At specified time intervals, the sperm were separated from the incubation medium by centrifugation, and the distribution of dipeptidyl peptidase (DPP II) and acrosin activity was determined by biochemically assaying the hydrolysis of trialanine and N-benzoyl-L-arginine ethyl ester (BAEE), respectively. When calcium was present, there was a significant increase in DPP II activity in the supernatants by 1 hour of incubation and a slight decline at later time points. This release was not correlated with false or normal acrosome reactions (loss of the acrosomal cap) monitored by phase-contrast microscopy but probably represents a very early stage in the normal acrosome reaction. This early stage is difficult to detect at the light microscope level because sperm are still in rouleaux and because membrane fusion is not directly observable. In contrast, acrosin activity, which was assayed in the same supernatants, increased at later times when sperm were observed to have completed normal acrosome reactions. The ultrastructural distribution of DPP II was determined in sperm pellets collected during in vitro incubation by using the DPP II substrate lysyl-alanyl-4-methoxy-2-naphthyamide. In freshly isolated cauda epidiymal sperm, reaction product is confined to the light-staining area in the dorsal bulge of the acrosome. However, by 1 hour of incubation, the light-staining area of many sperm was partially or completely dispersed, while other regions of the acrosome were unchanged. Our data are consistent with the conclusions that DPP II is a highly soluble component of the guinea pig sperm acrosome and that its release occurs during the initial phase of the acrosome reaction while sperm are still in rouleaux. Structural changes in the acrosome associated with DPP II release were detectable by electron microscopy but not by light microscopy. Acrosin, which is less soluble than DPP II, is released at a later time during the acrosome reaction. Both DPP II and acrosin appear to be partially inhibited following their release from sperm. A complete understanding of the sequential release and extracellular activities of the acrosomal enzymes will be necessary to fully define their functions in fertilization.