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H Ankel

Publications and source records attributed to H Ankel.

At least 37 records · Page 2Linked to original sources
PubMed1984

Binding of interleukin 2 to gangliosides.

Exogenous gangliosides inhibit interleukin 2 (IL2)-dependent growth of a T cell line, AKIL -1.E8. IL2 activity is retained by columns of ganglioside covalently linked to poly(L-lysine)-agarose and is not eluted with ethylene glycol but is completely recovered by elution with 1% SDS. The ability of gangliosides to inhibit IL2 activity is directly related to the complexity of their carbohydrate portion, and related ceramide derivatives at similar concentrations do not inhibit IL2 activity. We conclude that IL2 bound to exogenous gangliosides is inactive and that the carbohydrate portion of the ganglioside is crucial to its interaction with IL2.

Animals↗
PubMed1982

Inhibition of beta-interferon augmentation of murine natural killer cytotoxicity by gangliosides.

Interferons cause augmentation of natural killer (NK) cell activity, which might be a major reason for their antitumor effect. Antiviral and antigrowth effects of mouse beta interferon are inhibited by mono-, di-, and trisialogangliosides commonly found in brain extracts, but also in membranes of many other cells. Results presented in this report show that preincubation of mouse beta interferon with a brain ganglioside mixture or its isolated major components Gm1, Gd1a, Gd1b, and Gt1b (see Aberrations) prior to addition to effector spleen cells, inhibits NK-cell enhancement due to interferon in a dose-dependent manner. When spleen cells are treated with individual gangliosides alone, spontaneous NK cell activity is not affected. Pretreatment of effector cells with gangliosides prior to addition of interferon does not inhibit subsequent augmentation of NK cell activity by beta interferon. Also, target susceptibility remains unaltered in the presence of gangliosides. Thus the inhibitory effect of gangliosides appears to involve competition for interaction of beta interferon with the NK cells.

Animals↗
PubMed1982

Inhibition of mouse fibroblast interferon by gangliosides. Differential effects on biological activity and on induction of (2'--5')oligoadenylate synthetase.

Gangliosides are potent inhibitors of the antiviral activity of mouse fibroblasts and other beta-interferons. We have compared the effects of gangliosides on antiviral and antigrowth activities of mouse fibroblast interferon and on the induction of (2'--5')oligoadenylate synthetase, one of the enzymes implicated in the antiviral state induced by interferon. Whereas both biological effects appear to be inhibited by gangliosides in an analogous fashion, inhibition of induction of (2'--5')oligoadenylate synthetase does not correlate with inhibition of vesicular stomatitis virus replication. Ganglioside concentrations that inhibit the interferon-induced (2'--5')oligoadenylate synthetase to levels close to those of uninduced cells, still allow for a 100--1000-fold reduction of viral yield. Significantly higher ganglioside concentrations are required to prevent completely the antiviral effect. This biphasic relationship between (2'--5')oligoadenylate synthetase levels and inhibition of viral yield suggests that no or very small increases in synthetase levels are involved in inhibition of virus by between two and three orders of magnitude.

2',5'-Oligoadenylate Synthetase↗
PubMed1980

Mouse fibroblast (type I) and immune (type II) interferons: pronounced differences in affinity for gangliosides and in antiviral and antigrowth effects on mouse leukemia L-1210R cells.

Different interferons can be obtained from the same animal species depending on the cells and (or) the inducers used. Interferons of type I and type II differ not only antigenically but also in molecular weight and stability at low pH. We have investigated whether mouse type I and type II interferons also differ in properties relating to their biological action. We present evidence which suggests that the molecular mechanism leading to antiviral and antigrowth effects induced by both types of interferon in susceptible cells must differ in at least one important step. Antiviral and antigrowth activities of type I but not of type II interferon are both inhibited when gangliosides are added to cell cultures together with the interferon. Whereas type I interferon strongly binds to ganglioside affinity columns and can be eluted with solutions of N-acetylneuraminyllactose, type II interferon passes through such columns unretarded. L-1210 mouse leukemia cells (L-1210S) respond equally well to antiviral and antigrowth activities of type I and type II interferons. Type I interferon-resistant L-1210 cells (L-1210R), derived from L-1210S cells after continuous culture in the presence of mouse fibroblast interferon, lack antiviral and antigrowth response to mouse type I interferon [Gresser, I., Bandu, H.T. & Brouty-Boyé, D. (1974) J. Natl. Cancer Inst. 52, 553-559]. However, these cells display the same sensitivity toward type II interferon as do the parent L-1210S cells from which they were derived and respond equally well to its antiviral and antigrowth activities.

Animals↗
PubMed1977

Separation and allosteric properties of two forms of UDP-glucuronate carboxy-lyase.

DEAE-cellulose chromatography of partially purified preparations of UDP-glucuronate carboxy-lyase from wheat germ results in the separation of two forms of the enzyme. Both are fully active in the absence of added DPN, have indistinguishable molecular weights (210,000), but differ in charge and kinetic properties. Both are cooperatively activated by UDP-glucuronate, however Enzyme 1 is activated at lower concentrations than Enzyme 2. At low substrate concentrations (less than or equal to 5 micron), both enzymes are activated by UDP-glucose, 2 mM concentrations of activator increasing the activity of Enzyme 1 2-fold and of Enzyme 2 2.5-fold. UDP-xylose allosterically inhibits both enzymes. At substrate concentrations equal to the apparent Km values, inhibition of Enzyme 1 is much greater than that of Enzyme 2 (83 and 28% at 0.33 mM inhibitor concentration). The data suggest that synthesis of UDP-xylose is controlled both by substrate activation and product inhibition of UDP-glucuronate carboxy-lyase. The existence of a "more active" and a "less active" species of the enzyme suggests the possibility of two interconvertible forms of the same protein and the involvement of such interconversion in further regulation of UDP-xylose biosynthesis. However it is equally possible that both represent true isoenzymes.

Allosteric Regulation↗
PubMed1977

UDP-glucuronate carboxy-lyase in cultured chondrocytes.

UDP-glucuronate carboxy-lyase has been demonstrated in chick chondrocytes in tissue culture. It occurs in the particulate fraction, and its activity is stimulated by exogenous NAD. The enzyme is allosterically activated by UDP-glucuronate and inhibited by UDP-xylose, n Values of 2.8 indicate positive cooperativity of at least three interacting sites on the enzyme. These data suggest that UDP-xylose concentration in chondrocytes is regulated by substrate activation and product inhibition of UDP-glucuronate carboxy-lyase. Activity levels of the enzyme during growth of the cells peak towards mid-log phase and decline thereafter, closely paralleling levels of chondroitin sulfate glycosyltransferases determined previously (Schwartz, N. B. (1976) J. Biol. Chem. 251, 3346-3351). Thus, it appears that during chondrocyte development a common mechanism governs induction of glycosyltransferases and of UDP-glucuronate carboxy-lyase.

Animals↗
PubMed1977

Membrane receptors for interferon.

Specific cell membrane receptors for interferon have been postulated based on a variety of different observations, such as the following: trypsin treatment of monkey-mouse hybrid cells preferentially destroys sensitivity to primate interferon (9); syngeneic mice immunized with human-mouse hybrid cells develop surface-directed antibodies, which only block antiviral action of human interferon (24); interferon covalently bound to Sepharose beads retains its antiviral activity despite the fact that diameters of the beads are several times those of the cells (1,10,19); cells challenged with polyl:C to produce interferon do not develop resistance to viral infection in the presence of interferon antiserum (30). Interferon has a strong and specific affinity for the carbohydrate side chain of cell membrane gangliosides. Preincubation of Sepharose-bound interferon with gangliosides inhibits antiviral activity in the following order of potency: GM2 greater than or equal to GTl greater than GMl greater than or equal to GDla (3). Derivatives of GM2 lacking either terminal N-acetyl-galactosamine or terminal N-acetyl-neuraminic acid are not (or very little) inhibitory; in addition, binding to gangliosides is reversed by N-acetyl-neuraminyl-lactose, the trisaccharide common to all gangliosides. These data clearly demonstrate interferon's specificity for the carbohydrate moiety of the ganglioside molecule (6). Phaeseolus vulgaris lectin, which blocks antiviral action of interferon (4), also prevents binding of interferon to ganglioside-Sepharose affinity columns (2). Many substances of known affinity for gangliosides likewise inhibit action of interferon. These include cholera (15) and tetanus toxins (2), thyrotropin (5,23) and human chorionic gonadotropin (5). Although a more general effect on the state of the membrane or on cellular metabolism by these substances cannot be ruled out, competition for interferon binding sites appears to be the most plausible explanation. Increased sensitivity of certain transformed cells to interferon upon uptake of exogenous gangliosides not only supports the concept that these glycolipids are involved in binding of interferon to the membrane, but furthermore points to the importance of interferon-ganglioside interaction for triggering of the antiviral response (29).

Cell Membrane↗
PubMed1975

Cryptococcus laurentii cell envelope glycoprotein. Evidence for separate oligosaccharide side chains of different composition and structure.

Particulate enzyme preparations of the fungus imperfectus Cryptococcus laurentii catalyze transfer of mannosyl and galactosyl residues from GDP-[14C]mannose and UDP-[3H]-galactose to the same endogenous acceptor. After solubilization with pronase, the major portion of both labels is retarded on Sepharose columns and forms a symmetrical peak, in which 14C and 3H coincide. Label also coincides with endogenous protein and carbohydrate. Both labels bind to Sepharose-Concanavalin A (Con A) and are eluted with alpha-methylglucoside. After beta elimination with NaOH-NaBH4 only 14C label retains binding to Sepharose-Con A; 3H label representing (6-O-alpha-galactosyl)10-O-beta-galactosyl-O-mannitol as previously reported (Raizada, M. K., Kloepfer, H. G., Schutzbach, J. S., and Ankel, H. (1974) J. Biol. Chem. 249, 6080-6086) no longer binds. The [14C]mannose-containing material after beta elimination yields a pentasaccharide and a trisaccharide. Similar penta- and trisaccharides can be isolated following beta elimination of particulate preparations of the organism after pronase treatment. Analytical data suggest that the structure of the isolated pentasaccharides corresponds to that of a pentasaccharide previously synthesized de novo using cell-free enzyme preparations of the organism: 2-O-alpha-mannosyl-6-O-alpha-mannosyl-3-O-alpha-mannosyl-(2-O-beta-xylosyl)-O-mannose (Schutzbach, J. S., Raizada, M. K., and Ankel, H. (1974) J. Biol. Chem. 249, 2953-2958). The trisaccharide has the structure 2-O-alpha-mannosyl-2-O-alpha-mannosyl-O-mannitol. The data are consistent with a glycoprotein structure in which these three types of oligosaccharides are bound to a common polypeptide core through O-glycosidic linkages to threonyl and seryl residues.

Cell Membrane↗