PubMed Health⌕ Search

Biomedical subjects

I Ziegler

Publications and source records attributed to I Ziegler.

At least 55 records · Page 3Linked to original sources
PubMed1989

Regulation of tetrahydrobiopterin synthesis during lectin stimulation of human peripheral blood lymphocytes.

Lectin stimulation of human T lymphocytes causes a 7-fold increase in the specific activities of GTP-cyclohydrolase and a 4-fold increase in the specific activities of sepiapterin reductase. GTP-cyclohydrolase activities are maximal after 48 h and subsequently decline, whereas sepiapterin reductase activities continue to increase during the 72 h period measured. The specific activities of 6-pyruvoyltetrahydropterin synthase remain unchanged upon stimulation. Tetrahydrobiopterin synthesis during blast transformation is thus directed by both GTP-cyclohydrolase and sepiapterin reductase.

Alcohol Oxidoreductases↗
PubMed1989

Biosynthesis of tetrahydrobiopterin: a sensitive assay of 6-pyruvoyltetrahydropterin synthase using [2'-3H]dihydroneopterin 3'-triphosphate as substrate.

Pyruvoyltetrahydropterin synthase catalyzes the release of tritiated water from [2'-3H]dihydroneopterin 3'-triphosphate. The tritiated water formed during the enzymatic reaction is separated from substrate by adsorption of the latter to activated charcoal. The sensitivity and specificity of the assay allows the determination of the enzyme in crude cell extract.

Adsorption↗
PubMed1989

Modulation of interleukin 2 high-affinity binding by lymphocyte-derived tetrahydrobiopterin: pterins as potential participants in the control of interleukin 2 receptor assembly.

In this report, we have examined whether (6R)-tetrahydrobiopterin (H4biopterin) modulates the binding of interleukin 2 to high-affinity sites of the cloned mouse cytotoxic T-lymphocyte clone CTLL-2. Scatchard plot analysis of the equilibrium binding data reveals increased affinity when the cells are exposed simultaneously to interleukin 2 and to the pterin. The Kd values are statistically significantly reduced from 1.4 x 10(-11) M to 0.78 x 10(-11) M interleukin 2. The dissociation kinetics of the ligand were followed at 4 degrees C after equilibrium binding under high-affinity conditions (1.2 x 10(-10) M interleukin 2). In the presence of H4 biopterin, the dissociation rate constant (k-1) decreases from 6.2 x 10(-3) min-1 to 3.0 x 10(-3) min-1 and the half-time for dissociation increases from 106.8 min to 218.0 min. As a third approach interleukin 2 was bound to the surface of cells under high-affinity conditions by incubation in the cold and the internalization kinetics upon warming were determined. Sigmoidal-shaped kinetics of endocytosis in control cells indicate that the internalization rates increase only gradually. The presence of H4 biopterin causes an apparent immediate transition from higher-order kinetics to a linear response so that maximum internalization rates are reached immediately upon warming. The data show that lymphocyte-derived H4 biopterin in vitro at concentrations ranging from 2-8 x 10(-7) M modulates interleukin 2 high-affinity binding and that H4 biopterin potentially participates in the control of interleukin 2 receptor assembly.

Binding Sites↗
PubMed1988

Inhibition of monocyte luminol-dependent chemiluminescence by tetrahydrobiopterin, and the free radical oxidation of tetrahydrobiopterin, dihydrobiopterin and dihydroneopterin.

Luminol-dependent chemiluminescence of normal human monocytes activated by zymosan is demonstrated to be inhibited by tetrahydrobiopterin in a concentration-dependent manner. The reduced pterins tetrahydrobiopterin, dihydrobiopterin, and dihydroneopterin are all shown to be readily oxidized by the hydroxyl radical. The susceptibility of reduced pterins to free radical attack may explain the inhibition of chemiluminescence observed and an additional role of reduced pterins as free radical scavengers in tissues is considered.

Ascorbic Acid↗
PubMed1988

Identification of pigment cells during early amphibian development (Triturus alpestris, Ambystoma mexicanum).

The purpose of the present investigation was to provide and apply a methodological manual with which the distribution, patterning and relationship of melanophores and xanthophores can be analyzed during early amphibian development. For demonstration of the methods, which include ultrastructural, histochemical and biochemical approaches, Triturus alpestris and Ambystoma mexicanum (axolotl) embryos are used. These two species differ conspicuously in their larval pigment patterns, showing alternating melanophore bands in horizontal (T. alpestris) and vertical (axolotl) arrangements. With transmission- and scanning electron microscopy melanophores and xanthophores were distinguished by their different pigment organelles and surface structures. The presence of phenol oxidase (tyrosinase) was used to reveal externally invisible or faintly visible melanophores by applying an excess of 3,4 dihydroxy-phenylalanine (dopa). Xanthophores were made visible in fixed and living embryos by demonstrating their pterin fluorescence. In addition, pterins were analyzed by HPLC in embryos before and after pigmentation was visible.

Ambystoma↗
PubMed1987

[Pterins: pigments, cofactors and signal connections in cell interactions].

Pteridines were originally described as pigments of insects and lower vertebrates. The electron-donating function of tetrahydrobiopterin for aromatic amino acid hydroxylation and thus, for neurotransmitter biosynthesis adduced the participation of unconjugated pterins in cellular metabolism. There has been increasing evidence moreover that they are signal molecules for intercellular recognition in primitive eucaryotes, as well as modifiers of signal polypeptides in higher vertebrates.

Animals↗
PubMed1987

Biopterin synthesis in mouse spleen during bone marrow transplantation correlates with unimpaired hemopoietic engraftment.

Normal engraftment of bone marrow transplants depends on histocompatibility between donor and recipient. In this case reconstitution of hemopoiesis and lymphopoiesis in the mouse spleen is correlated with transient biopterin synthesis in these cells. Allogeneic bone marrow progeny cells undergo donor cell proliferation in the spleen prior to the incidence of graft-versus-host reaction. These cells are not committed to biopterin synthesis. Thy-1 monoclonal antibody fully repairs engraftment of allogeneic transplants together with biopterin synthesis.

Animals↗
PubMed1986

Phorbol ester causes short term and transient accumulation of pteridines in T cells and in cell lines.

Upon exposure to 12-O-tetradecanoylphorbol 13-acetate, interleukin 2 receptor+ T cells transiently accumulate neopterin and biopterin as was determined by HPLC after iodine oxidation of acidic cell extracts. Pteridines peak at maximally 20 fold levels after 10-20 min and return to initial levels during the following 30-40 min. Resting human peripheral blood mononuclear cells do not react within this short period. TPA elicits similar neopterin and biopterin accumulation kinetics in cell lines such as HL-60, Reh, Jurkat JMN, HeLa and 293, whereby HL-60 and Reh release substantial amounts of these transiently formed pteridines into the medium.

Biopterins↗
PubMed1986

Pteridines are produced during interleukin 2-induced T-cell proliferation and modulate transmission of this signal.

Pteridine levels of interleukin 2 (IL-2) receptor+ T-cell populations have been determined by HPLC after iodine oxidation; neopterin was monitored in the culture supernatants by radio-immunoassay. Upon addition of IL-2, cellular levels of biopterin and 6-hydroxymethylpterin rise transiently from 0.02 to 0.9 pmol/10(6) cells, cellular levels of neopterin from 1.5 to 4.1 pmol/10(6) cells. They peak at 8 and 13 h, respectively, after exposure to IL-2. Neopterin is not accumulated in the culture supernatant. DNA synthesis in T cells begins 10-12 h after adding the lymphokine and the portion of cells that undergo S-phase transition gradually increases during the subsequent 10 h. Entry into DNA synthesis phase is markedly accelerated if IL-2 is supplied together with tetrahydrobiopterin (0.8-1.6 X 10(-6) M) and the kinetics of entry into the S-phase transition during the period of 6-20 h become linear. This indicates that tetrahydrobiopterin modulation of IL-2 activity (Ziegler, I. et al. Naturwiss 72 (1985) 330) is an early event occurring during IL-2 signal transmission.

Biopterins↗
PubMed1985

Synthesis and interferon-gamma controlled release of pteridines during activation of human peripheral blood mononuclear cells.

Lectin stimulation of human peripheral blood mononuclear cells causes an increase in neopterin, biopterin, 6-hydroxymethylpterin and 6-formylpterin, as was determined by HPLC after iodine oxidation of the acid extract. After 72 h, pteridines peak at levels 5-10 fold as compared to resting cells. Levels decline to initial values during the following 24 h. Changes in pteridine proportions indicate that the synthesis of tetrahydrobiopterin proceeding from dihydroneopterin triphosphate is controlled during the process of lymphocyte activation. The release of both cellular neopterin and biopterin, but not of 6-hydroxymethylpterin and its aldehyde, is controlled by interferon-gamma.

Animals↗
PubMed1985

Pteridine formation during lectin-induced lymphocyte activation.

After iodine oxidation, biopterin, 6-hydroxymethylpterin, and 6-formylpterin were identified in mouse spleen lymphocytes by means of reverse-phase HPLC, Crithidia assay, and oxidative degradation. Concanavalin A activation induces a 30-fold increase in the pteridine amounts; biopterin as well as the sum of the carbinol and the aldehyde attain levels of 6-8 X 10(-12) mol/10(6) cells. The most rapid increase occurs during the first 24 hr. Thus, pteridine accumulation precedes the period of lymphocyte proliferation; maximum DNA synthesis was found after 72 hr. Biopterin remains largely inside the cells, whereas 6-hydroxymethylpterin and 6-formylpterin were found in the supernatant if the stimulated cells were subsequently incubated in a phosphate buffered salt solution (PBS). Isoxanthopterin was found in the PBS supernatant of control cells that previously were kept in medium alone rather than subjected to lectin stimulation. Only minimal amounts were found inside these cells, and this pterin was absent from the stimulated lymphocytes. The early increase in cellular pteridines and their differential release may well provide the basis for their modulating effect on interleukin-2 activity (Ziegler I, et al: Lymphokine Research 3:284, 1984).

Animals↗
PubMed1984

Pterins and the regulation of lymphocyte activation on the mode of xanthopterin action.

Some intermediates of pterin anabolism amplify the lectin-induced lymphocyte stimulation while the catabolites xanthopterin and isoxanthopterin terminate their proliferation (Ziegler, I. et al., Cancer Res. 43, 5356 (1983). In the present investigation, we analysed the effect of xanthopterin on total RNA synthesis and on DNA synthesis in both concanavalin A-stimulated lymphocytes and in the lymphoblastoid cell line L 1210. The time courses at various inhibitor concentrations indicated that xanthopterin inhibits RNA synthesis prior to DNA synthesis. Further analysis of the RNA species was performed by double-labeling and subsequent polyacrylamide-gel electrophoresis. Pulse and pulse-chase experiments revealed that an inhibition of 45 S pre-RNA is closer to the target of xanthopterin inhibition than is DNA synthesis.

Animals↗
PubMed1983

Participation of pterins in the control of lymphocyte stimulation and lymphoblast proliferation.

Biopterin accumulation had been demonstrated as the result of normal and, especially, of malignant hemopoietic cell proliferation (Ziegler, I. et al. Blut, 44: 231-240, and 261-270, 1982). Among 13 major intermediates of pterin metabolism and two lumazines, xanthopterin (but not dihydroxanthopterin) was found to inhibit cell proliferation (half-maximum inhibition at 1.8 X 10(-5) M) during concanavalin A-induced lymphocyte activation in pre-stimulated lymphocytes and in a lymphoid cell line grown in continuous culture (LS-2). LS-2 cells exposed to maximum inhibitor concentrations largely maintained the initial thymidine incorporation rate for about 40 hr but failed to enter logarithmic growth. Isoxanthopterin inhibition was found only in serum-free medium, since it is trapped by the alpha-acid glycoprotein present in the serum. The reduced biopterin derivatives, sepiapterin, dihydrobiopterin, and tetrahydrobiopterin, are costimulators during concanavalin A-induced lymphocyte activation. Their costimulatory effect follows an optimum curve and peaks at 1.5 to 3 X 10(-5) M. It is highest at the suboptimal and supraoptimal concanavalin A concentration. The D-erythro isomer dihydroneopterin was inactive. The results indicate that the anabolic-reduced biopterin derivatives are not simply lymphocytic products, but, in combination with the catabolites xanthopterin and isoxanthopterin, they also participate in the regulation of lymphocyte activation. Hence, they fulfill the criteria for lymphokines.

Animals↗
PubMed1982

Biopterin level in peripheral blood cells as a marker for hemopoietic cell proliferation during leukemia and polycythemia vera.

Using the Crithidia assay 3.0 ng biopterin/ml blood was found, of which one third was present in the plasma. The erythrocyte fraction comprised 1.7 ng and the buffy coat 0.33 ng. After Ficoll separation 0.050 ng were found in the lymphocyte layer of 1 ml blood. During blast crisis of chronic myelocytic leukemias increased amounts of biopterin were found in the erythrocyte fraction and in the buffy coat. The high biopterin concentration per unit of protein in the white cell fraction indicated the presence of blasts. In Polycythemia vera increased amounts of biopterin in both the red cell fraction and in the buffy coat were also found but the percentage distribution within total cellular biopterin was markedly shifted toward the erythrocyte fraction. In cases of chronic and acute lymphocytic leukemias the low amounts of biopterin in the red cell fraction agreed with the current view of partial extinction of the erythropoietic line. The isolated lymphoblasts were characterized by high biopterin concentrations per unit of protein. During remission the biopterin patterns approached normal levels.

Biopterins↗
PubMed1982

Biopterin level in blood cells as a marker for hemopoietic cell proliferation during autologous bone marrow transplantation in beagle dogs.

Bone marrow aplasia was induced by fractionated whole body irradiation with 3000 R and restitution was started by autologous bone marrow transplantation. During the period of aplasia the amount of buffy coat biopterin clearly followed the decline of leukocytes and, vice versa, during reconstitution it largely paralleled their increase in number. The amount of red cell biopterin closely correlated with the number of reticulocytes rather than with the fairly constant values for hematocrit or of erythrocytic protein. Thereby it clearly followed the various periods of red cell recovery. The amount of cellular biopterin, its concentration with respect to cell number or to unit of protein and the percentage distribution of biopterin among the cell fractions are presented as characteristics of the activity of hemopoietic cell proliferation.

Animals↗
PubMed1982

Pteridine-binding alpha 1-acid glycoprotein from blood of patients with neoplastic diseases.

A glycoprotein was selectively enriched in the supernatant (Fraction b) obtained by alcohol and trichloroacetic acid fractionation of digitonin extracts from blood of patients with neoplastic diseases and of control subjects. Subsequent chromatography with concanavalin A:Sepharose separated a concanavalin A-reactive fraction from a concanavalin A-nonreactive one. In sodium dodecyl sulfate gel electrophoresis, the fractions from both malignant origin as well as control subjects appeared as single bands showing the same mobility. They were identical with the band obtained from commercial alpha 1-acid glycoprotein. In Fraction b of malignant origin, greatly increased amounts of the alpha 1-acid glycoprotein from malignant cases (AGPM) were found as compared to alpha 1-acid glycoprotein from controls (AGPC). Furthermore, AGPC had a higher glycine content than did AGPM. The electrofocusing pattern of AGPM showed additional bands between pH 3.7 and 4.4, whereas AGPC and commercial alpha 1-acid glycoprotein focused between pH 3.2 and 3.8. In contrast to AGPC and to a commercial alpha 1-acid glycoprotein, AGPM is characterized by a chromophoric group with maximal absorbance at 400 nm. It could be detached by treatment with 6 M guanidine hydrochloride thus indicating a noncovalent binding. The spectral data on the separated chromophore at pH 0.5 agreed with that of a 6,7-substituted pteridine. After detachment with reducing agents, a pteridine in its 7,8-dihydro form was indicated by spectral analysis.

Amino Acids↗