Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.4.99.7 (sialyltransferase)
1,534 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After the observation that human mAb 32-27M reacts only with melanoma and astrocytoma cells cultured in the presence of fetal bovine serum, a novel pathway for the uptake of exogenous gangliosides, their further biosynthesis, and expression at the cell surface as novel Ag has been elucidated. The addition of fetal bovine serum to melanoma and astrocytoma cells growing in synthetic medium (insulin-transferrin-selenium) resulted in reactivity with Ab32-27M. As antibody 32-27M detects N-glycolylneuraminic acid (NeuGc)-containing gangliosides, the effect of adding a number of different gangliosides to melanoma and astrocytoma cells cultured in the synthetic medium was studied. Only the addition of NeuGc-GM3 resulted in the development of Ab32-27M reactivity. The identity of the antigenic structures developed after addition of fetal bovine serum or NeuGc-GM3 was determined by analysis of the gangliosides from both samples. The major component detected in melanoma cell lines was shown to be N-acetylneuraminic acid-NeuGc-GD3. Another, slower moving component, present in some melanomas and in astrocytomas may be N-acetylneuraminic acid-NeuGc-GD2. The cell type specificity for these processes can be most readily explained by postulating that all cells can take up exogenous gangliosides but only melanoma and astrocytoma cells have sufficiently high levels of GM3 alpha 2----8-sialyltransferase for the conversion of added NeuGc-GM3 to disialogangliosides to be effective. These results demonstrate a novel pathway for exogenous glycolipid processing that can lead to novel Ag expression but may also play a role in normal glycolipid metabolism and function.
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PMID:The addition of exogenous gangliosides to cultured human cells results in the cell type-specific expression of novel surface antigens by a biosynthetic process. 246 27

We are interested in determining whether carbohydrates are important regulatory determinants in the intracellular transport and secretion of glycoproteins. In the present study, we have used swainsonine, an indolizidine alkaloid, to modify the structure of N-glycosidically linked complex oligosaccharides. By inhibiting Golgi mannosidase II, swainsonine prevents the trimming of GlcNAc(Man)5(GlcNAc)2 to GlcNAc-(Man)3(GlcNAc)2, resulting in the formation of hybrid-type oligosaccharides. We find, from pulse-chase experiments using [35S]methionine and immunoprecipitation of individual proteins from culture media, that swainsonine treatment (1 microgram/ml) accelerated the secretion of glycoproteins (transferrin, ceruloplasmin, alpha 2-macroglobulin, and alpha 1-antitrypsin) by decreasing the lag period by 10-15 min relative to untreated cultures. The enhanced secretion was specific for glycoproteins since the secretion of albumin, a nonglycoprotein, was unaffected. When alpha 1-antitrypsin was immunoprecipitated from the cell lysates, sodium dodecyl sulfate-polyacrylamide gel electrophoresis fluorographic analysis demonstrated that the conversion of the high-mannose precursor to the hybrid form in swainsonine-treated cells occurred more rapidly (by about 10 min) than the conversion to the complex form in control cells. Since both the hybrid and complex forms of alpha 1-antitrypsin are terminally sialylated by sialyltransferase in the trans-Golgi, these results suggest that swainsonine-modified glycoproteins traverse the Golgi more rapidly than their normal counterparts. Therefore, accelerated transport within this organelle may account for the decreased lag period of glycoprotein secretion in the swainsonine-treated cultures.
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PMID:Swainsonine treatment accelerates intracellular transport and secretion of glycoproteins in human hepatoma cells. 257 69

The effect of a single administration and a 6-week treatment with ethanol on rat liver sialyltransferase activity towards asialoglycoproteins and N-acetyllactosamine (Gal beta 1,4GlcNAc) was studied. Since only the alpha 2,6-sialyltransferase is involved in the in vivo sialylation of transferrin, Gal beta 1,4GlcNAc was chosen as an acceptor and alpha 2,6-sialyl-N-acetyllactosamine was separated from the corresponding alpha 2,3-sialyl isomer present in the sialyltransferase reaction mixture by high-performance liquid chromatography. After a single ethanol administration there was a low (about 20%) but significant (p less than 0.005) reduction of sialyltransferase activity towards asialotransferrin as well as a reduced alpha 2,6-sialyltransferase activity towards N-acetyllactosamine. An opposite result was found in the chronically ethanol-treated rats: in these animals either the total or alpha 2,6-sialyltransferase activity was slightly higher than in control animals. Blood ethanol concentration was significantly high (3.3 +/- 1.2 mg/ml) only in the acute-treated animals, suggesting that the accumulation in the body of ethanol and/or its metabolites induces a reduction of liver alpha 2,6-sialyltransferase activity responsible for the transferrin sialylation. Current results are consistent with the finding (Stibler H, Hultcrantz R: Alcohol Clin Exp Res 11:468-473, 1987) that an enhanced level of hyposialylated transferrin isoforms is a marker of present but not previous alcohol abuse.
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PMID:Effect of acute and chronic ethanol administration on rat liver alpha 2,6-sialyltransferase activity responsible for sialylation of serum transferrin. 268 63

The intracellular movement of cell surface transferrin receptor (TfR) after internalization was studied in K562 cultured human erythroleukemia cells. The sialic acid residues of the TfR glycoprotein were used to monitor transport to the Golgi complex, the site of sialyltransferases. Surface-labeled cells were treated with neuraminidase, and readdition of sialic acid residues, monitored by isoelectric focusing of immunoprecipitated TfR, was used to assess the movement of receptor to sialyltransferase-containing compartments. Asialo-TfR was resialylated by the cells with a half-time of 2-3 h. Resialylation occurred in an intracellular organelle, since it was inhibited by treatments that allow internalization of surface components but block transfer out of the endosomal compartment. Moreover, roughly half of the resialylated molecules were cleaved when cells were retreated with neuraminidase after culturing, indicating that this fraction of the molecules had returned to the cell surface. These results suggest that TfR is transported from the cell surface to the Golgi complex, the intracellular site of sialyltransferases, and then returns to the cell surface. This pathway, which has not been previously described for a cell surface receptor, may be different from the route followed by TfR in iron uptake, since reported rates of transferrin uptake and release are significantly more rapid than the resialylation of asialo-TfR.
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PMID:Intracellular movement of cell surface receptors after endocytosis: resialylation of asialo-transferrin receptor in human erythroleukemia cells. 298 85

The recycling of cellular glycoproteins to the site of Golgi mannosidase I, an enzyme of asparagine-linked oligosaccharide synthesis, was studied in K562 human erythroleukemia cells. Cells were metabolically labeled in the presence of deoxymannojirimycin, a reversible inhibitor of Golgi mannosidase I. This generates glycoproteins with immature oligosaccharides in their normal locations. Transport to the mannosidase I compartment was then assessed by testing for the conversion of oligosaccharides into mature forms during reculture without deoxymannojirimycin. Transferrin receptor (TfR) was acted on by mannosidase I during reculture, suggesting that it returned to the region of the Golgi complex where this enzyme resides. The slow rate of this transport (t1/2 greater than 6 h) implies that it is probably different than TfR movement during transferrin internalization (t1/2 = 10-20 min) and TfR transport to the sialyltransferase compartment in the Golgi complex (t1/2 = 2-3 h) (Snider, M. D., and O. C. Rogers, 1985, J. Cell Biol., 100:826-834). The total cell glycoprotein pool was also transported to the mannosidase I compartment with a half-time of 4 h. Because this transport is 5-10 times faster than the rate of de novo glycoprotein synthesis in these cells, it is likely that most of the glycoprotein traffic through the Golgi complex is composed of recycling molecules.
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PMID:Membrane traffic in animal cells: cellular glycoproteins return to the site of Golgi mannosidase I. 301 99

Lymph node (LN) T cells from autoimmune MRL/MpJ-lpr/lpr (lpr) mice and control MRL/MpJ-+/+ (+/+) mice were compared as to their cell surface lectin-binding sites and glycosyltransferase activities. T cells from enlarged LN of lpr mice expressed a higher amount of binding sites for lectins reactive to mucin-type sugar chains than normal +/+ mouse T cells. Correspondingly, glycosyltransferase activities involved in the biosynthesis of mucin-type sugar chains were higher in lpr mouse T cells than in +/+ T cells. The activities of UDP-N-acetylgalactosamine (GalNAc):polypeptide GalNAc transferase and UDP-galactose (Gal):asialo bovine submaxillary mucin (BSM) Gal transferase were found to be elevated. The activity of UDP-Gal:asialo-agalacto transferrin Gal transferase, which is involved in the biosynthesis of complex type sugar chains, was also increased in lpr mice but to a smaller extent than the mucin-type Gal transferase activities. An abnormality in sialyltransferase activity was also found in lpr T cells.
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PMID:Enhancement of the activities of glycosyltransferases involved in the biosynthesis of mucin-type sugar chains in autoimmune MRL lpr/lpr mouse T cells. 313 57

The existence of a brain sialyltransferase catalyzing the specific transfer of NeuAc on native fetuin was demonstrated. This enzyme was not able to sialylate either asialofetuin or desialylated and nondesialylated orosomucoid, transferrin, and bovine submaxillary mucin. It required the presence of Mn2+ for optimal activity. Moreover, in fetuin, this activity was closely related to the proportion of NeuAc residues, but in liver tissue sialylation occurred only onto asialofetuin. In native fetuin, sialylation took place on O-glycan chains to give an O-disialyltetrasaccharidic structure. The Gal----GalNAc----protein was not an acceptor, but alpha-NeuAc-(2----3)-Gal----GalNAc----protein was, suggesting a specific transfer alpha-(2----6) to the GalNAc residue.
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PMID:A brain sialyltransferase having a narrow specificity for O-glycosyl-linked oligosaccharide chains. 373 Nov 79

Carbohydrate-deficient transferrin (CDT) is now considered to be the most sensitive and specific biological marker of alcohol abuse. However, the mechanism by which chronic alcohol consumption causes an elevation of CDT levels in serum is still not understood. Therefore, we fed eight pairs of male rats a nutritionally adequate liquid diet containing either alcohol (36% of energy) or isocaloric dextrose (control) for 4 weeks, after which blood and liver samples were obtained. Serum CDT content in alcohol-treated rats increased by 45% (P < .05) in ethanol-fed animals compared with their corresponding controls. In contrast, in rats fed ethanol, the activities of sialyltransferase (ST), galactosyltransferase (GT), and N-acetylglucosamine transferase (N-AGT), which are glycosyltransferases involved in transferrin carbohydrate side chain synthesis, were diminished by 24% and 40% (P < .05), 23% and 51% (P < .05, .001), and 20% and 26% (P < .05) in total liver homogenates and Golgi fraction (GF) 1, respectively, when expressed as units/100 g body weight. These enzymes were also significantly less active in hepatic GFs 2 and 3. The depression of the transferase activities in ethanol-fed rats appeared to be due, at least in part, to enzyme inactivation by acetaldehyde, whereas ethanol itself was without effect. Similar results were obtained in humans: five alcohol abusers were found to exhibit a 23% decrease in hepatic sialyltransferase and a 41% increase in sialidase activities, respectively, when compared with three nondrinking subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum carbohydrate-deficient transferrin: mechanism of increase after chronic alcohol intake. 759 Jun 64

Transferrin is N-glycosylated glycoprotein and plays an important role in iron transport from sites of absorption and storage to sites of utilization. Chronic ethanol alters the normal microheterogeneity pattern of transferrin as a consequence of changes in the sialic acid content. However the underlying basis of this change in sialic acid contents of transferrin in alcohol abuse remains unclear. We have undertaken this study in order to investigate the effects of chronic ethanol in rats with respect to the hepatic rate of (i) transferrin synthesis based on labeled leucine incorporation, (ii) the incorporation of labeled N-acetyl mannosamine (NAM) into sialic acid residues of transferrin, and (iii) roles of specific sialyltransferase and sialidase at hepatic subcellular level. The results showed no significant difference in the incorporation of labeled leucine into transferrin at all levels between the control and ethanol group, whereas the incorporation of NAM into transferrin was significantly decreased by 84% (p < 0.001) both at the whole cell and Golgi level. Thus, the incorporation of labeled NAM relative to the incorporation of labeled leucine into hepatic transferrin was significantly decreased by 86% (p < 0.001) in chronic ethanol-treated animals as compared with the controls both at the whole cell golgi levels. These data are further supported by our finding of concomitant decrease in the activity of beta-galactoside alpha 2,6-sialyltransferase by 58% (p < 0.01) in ethanol-treated rats as compared with control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of chronic ethanol on enzymes regulating sialylation and desialylation of transferrin in rats. 833 87

In recent years, a number of studies have been reported that have clearly established that hepatic glycosylation machinery is affected by chronic ethanol treatment in rats. We have previously reported that chronic ethanol treatment in rats resulted in decreased glycosylation of transferrin and apolipoprotein E with concomitant decreases in enzymatic activities of Golgi galactosyltransferases and sialyltransferases. In all these studies investigators have invariably used the well-accepted dietary formulation of alcohol diet as proposed by Lieber and DeCarli. However, questions were raised whether the lower carbohydrate content in Lieber's alcohol diet may be responsible for observed effects of ethanol on hepatic glycosylation machinery. Therefore, to verify whether or not the crucial effects of chronic ethanol treatment on hepatic glycosylation machinery as observed in our studies, were truly caused by ethanol, we have extended our studies on protein glycosylation with the inclusion of a third dietary group that was compensated for carbohydrate content. In this investigation, rats were fed with three dietary regimen corresponding to control, ethanol, and carbohydrate compensated ethanol group and studies were done on (i) labeled leucine, galactose and N-acetylmannosamine incorporation into transferrin and apolipoprotein E, and (ii) hepatic galactosyltransferase and sialyltransferase activities in Golgi rich fraction in rat. Our results clearly showed that regardless of the carbohydrate content, marked decreases in the incorporation of labeled sugars into transferrin and the enzymatic activities of galactosyltransferase and sialyltransferase occurred in rats administered chronic ethanol. Thus, it is reasonable to conclude that it is not the carbohydrate content of the diet but ethanol per se, when administered chronically, greatly impairs the glycosylation machinery of rat liver and that the magnitudes of these effects are selectively specific with regard to the type of sugar or the glycosylation enzyme.
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PMID:Chronic ethanol induced impairment of hepatic glycosylation machinery in rat is independent of dietary carbohydrate. 904 76


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