Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In breast cancer, the O-glycans added to the MUC1 mucin are core 1- rather than core 2-based. We have analyzed whether competition by the glycosyltransferase, ST3Gal-I, which transfers sialic acid to galactose in the core 1 substrate, is key to this switch in MUC1 glycosylation that results in the expression of the cancer-associated SM3 epitope. Of the three enzymes known to convert core 1 to core 2, by the addition of GlcNAc to GalNAc in core1 C2GnT1 is the dominant enzyme expressed in normal breast tissue. Expression of C2GnT1 is low or absent in around 50% of breast cancers, whereas expression of ST3Gal-I is consistently increased. Mapping of ST3Gal-I and C2GnT1 within the Golgi pathway showed some overlap. To examine functional competition, the enzymes were overexpressed in T47D cells, which normally make core 1-based structures, have no detectable C2GnT1 activity and express the SM3 epitope. Overexpression of C2GnT1 resulted in loss of binding of SM3 to MUC1, accompanied by a decrease in the GalNAc/GlcNAc ratio, indicative of a switch to core 2 structures. Transfection of a C2GnT1 expressing line with ST3Gal-I restored SM3 binding and reduced GlcNAc incorporation into MUC1 O-glycans. Thus, even when C2GnT1 is expressed, the O-glycans added to MUC1 become core 1-dominated structures, provided expression of ST3Gal-I is increased as it is in breast cancer.
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PMID:The relative activities of the C2GnT1 and ST3Gal-I glycosyltransferases determine O-glycan structure and expression of a tumor-associated epitope on MUC1. 1111 34

Reactions of MnX2.nH2O with tris(N-(D-mannosyl)-2-aminoethyl)amine ((D-Man)3-tren), which was formed from D-mannose and tris(2-aminoethyl)amine (tren) in situ, afforded colorless crystals of [Mn((D-Man)3-tren)]X2 (3a, X = Cl; 3b, X = Br; 3c, X = NO3; 3d, X = 1/2SO4). The similar reaction of MnSO4.5H2O with tris(N-(L-rhamnosyl)-2-aminoethyl)amine ((L-Rha)3-tren) gave [Mn((L-Rha)3-tren)]SO4 (4d), where L-rhamnose is 6-deoxy-L-mannose. The structures of 3b and 4d were determined by X-ray crystallography to have a seven-coordinate Mn(II) center ligated by the N-glycoside ligand, (aldose)3-tren, with a C3 helical structure. Three D-mannosyl residues of 3b are arranged in a delta(ob3) configuration around the metal, leading to formation of a cage-type sugar domain in which a water molecule is trapped. In 4d, three L-rhamnosyl moieties are in a delta(lel3) configuration to form a facially opened sugar domain on which a sulfate anion is capping through hydrogen bonding. These structures demonstrated that a configurational switch around the seven-coordinate manganese(II) center occurs depending on its counteranion. Reactions of 3a, 3b, and 4d with 0.5 equiv of Mn(II) salt in the presence of triethylamine yielded reddish orange crystals formulated as [[Mn((aldose)3-tren)]2Mn(H2O)X3.nH2O (5a, aldose = D-Man, X = Cl; 5b, aldose = D-Man, X = Br; 6d, aldose = L-Rha, X = 1/2SO4). The analogous trinuclear complexes 6a (aldose = L-Rha, X = Cl), 6b (aldose = L-Rha, X = Br), and 6c (aldose = L-Rha, X = NO3) were prepared by the one-pot reaction of Mn(II) salts with (L-Rha)3-tren without isolation of the intermediate Mn(II) complexes. X-ray crystallographic studies revealed that 5a, 5b, 6c, and 6d have a linearly ordered trimanganese core, Mn(II)Mn(III)Mn(II), bridged by two carbohydrate residues with Mn-Mn separations of 3.845(2)-3.919(4) A and Mn-Mn-Mn angles of 170.7(1)-173.81(7) degrees. The terminal Mn(II) atoms are seven-coordinate with a distorted mono-face-capped octahedral geometry ligated by the (aldose)3-tren ligand through three oxygen atoms of C-2 hydroxyl groups, three N-glycosidic nitrogen atoms, and a tertiary amino group. The central Mn(III) atoms are five-coordinate ligated by four oxygen atoms of carbohydrate residues in the (aldose)3-tren ligands and one water molecule, resulting in a square-pyramidal geometry. In the bridging part, a beta-aldopyranosyl unit with a chair conformation bridges the two Mn(II)Mn(III) ions with the C-2 mu-alkoxo group and with the C-1 N-glycosidic amino and the C-3 alkoxo groups coordinating to each metal center. These structures could be very useful information in relation to xylose isomerases which promote aldose-ketose isomerization by using divalent dimetal centers such as Mn2+, Mg2+, and Co2+.
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PMID:Novel Mn(II)Mn(III)Mn(II) trinuclear complexes with carbohydrate bridges derived from seven-coordinate manganese(II) complexes with N-glycoside. 1127 63

Increased mucosal expression of TF, the Thomsen-Friedenreich oncofetal blood group antigen (galactose beta1-3 N-acetylgalactosamine alpha-) occurs in colon cancer and colitis. This allows binding of TF-specific lectins, such as peanut agglutinin (PNA), which is mitogenic to the colorectal epithelium. To identify the cell surface TF-expressing glycoprotein(s), HT29 and Caco2 colon cancer cells were surface-labeled with Na[(125)I] and subjected to PNA-agarose affinity purification and electrophoresis. Proteins, approximately 110-180 kDa, present in HT29 but not Caco2 were identified by Western blotting as high molecular weight splice variants of CD44 (CD44v). Selective removal of TF antigen by Streptococcus pneumoniae endo-alpha-N-acetylgalactosaminidase substantially reduced PNA binding to CD44v. Immunoprecipitated CD44v from HT29 cell extracts also expressed sialyl-Tn (sialyl 2-6 N-acetylgalactosaminealpha-). Incubation of PNA 15 microg/ml with HT29 cells caused no additional proliferative effect in the presence of anti-CD44v6 mAb. In colon cancer tissue extracts (N = 3) PNA bound to CD44v but not to standard CD44. These data show that CD44v is a major PNA-binding glycoprotein in colon cancer cells. Because CD44 high molecular weight splice variants are present in colon cancer and inflammatory bowel disease tissue but are absent from normal mucosa, these results may also explain the increased PNA reactivity in colon cancer and inflammatory bowel disease. The coexpression of oncofetal carbohydrate antigens TF and sialyl-Tn on CD44 splice variants provides a link between cancer-associated changes in glycosylation and CD44 splicing, both of which correlate with increased metastatic potential.
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PMID:Cell surface-expressed Thomsen-Friedenreich antigen in colon cancer is predominantly carried on high molecular weight splice variants of CD44. 1144 38

The first total synthesis of alpha-(2-->3)/alpha-(2-->6)-disialyl lactotetraosyl (DSLc4) ceramide and alpha-(2-->3)/alpha-(2-->6)-disialyl Lewis A (DSLe(a)) ganglioside as cancer-associated antigens is described. The suitably protected lactotriose (Lc3) derivatives were successively glycosylated with sialic acid, sialyl-alpha-(2-->3)-D-galactose and/or L-fucose donors in a regio- and stereo-selective manner, to give the protected type I hexa- and hepta-saccharides, respectively, which were then converted to the target gangliosides by the introduction of ceramide and subsequent complete deprotection.
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PMID:First total synthesis of alpha-(2-->3)/alpha-(2-->6)-disialyl lactotetraosyl ceramide and disialyl Lewis A ganglioside as cancer-associated carbohydrate antigens. 1266 6

It has been proposed that all ultrasonic vocalizations (USVs) in young rats are by-products of a cardiovascular response to decreased venous return, the abdominal compression reaction. To test the hypothesis, venous return was decreased in infant rats while USV and cardiovascular measures were monitored. Neither injection of the vasodilator sodium nitroprusside nor blood withdrawal from the superior vena cava or carotid artery elicited USV from pups in their home cage. Thus, decreased venous return by itself is not sufficient to elicit USV. To test whether venous return is a necessary mechanism for USV production, 5% dextrose in water or blood was infused intravenously into isolated pups that were producing USV. This artificial increase of venous return did not affect the rate of USV.
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PMID:Decreased venous return is neither sufficient nor necessary to elicit ultrasonic vocalizations of infant rat pups. 1293 68

The objective of this study was to compare the recovery of male rats after a major abdominal surgical procedure (the implantation of a radiotelemetry transmitter) when treated with buprenorphine, butorphanol, or ketoprofen and subcutaneous fluids (5% dextrose) or with subcutaneous fluids only. The parameters for assessing recovery were heart rate (HR), mean arterial blood pressure (MAP), home cage activity, food and water consumption, and body weight. HR, MAP, and activity were continuously monitored by radiotelemetry methods, food and water intakes were determined daily, and body weights were measured once or three times a week. In light of HR, nocturnal home cage activity, water consumption, and body weight gain, animals were recovered by about 7 days after surgery. MAP normalized by 1 to 2 days postsurgery, and food consumption returned to presurgical levels 5 to 12 days after surgery, depending on the analgesic treatment. On the basis of nocturnal activity, HR, and food and water intakes, buprenorphine-treated animals recovered more slowly than did the other two analgesic-treated groups. By the other parameters, all three analgesic-treated groups showed very similar responses across time. Surprisingly, when compared with the groups receiving only subcutaneous fluids, buprenorphine and butorphanol delayed or did not advance recovery, whereas ketoprofen neither retarded nor advanced recovery. Explanations for these results include: (a) the analgesics were effective in relieving pain but had pharmacological side effects that altered the measured parameters, making it difficult to determine recovery; (b) the level of pain experienced did not notably affect recovery; (c) the analgesics, at the doses and/or dosing schedules used, were not effective in the relief of pain, thereby causing both groups of animals to recover at the same rate; and (d) the analgesics interfered with recovery. Final resolution of these issues awaits further investigation.
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PMID:Recovery of male rats from major abdominal surgery after treatment with various analgesics. 1461 56

To establish an animal model of fatigue, we kept rats in a cage filled with water to a height of 1.5 cm. We selected a weight-loaded forced swimming test for evaluation of the extent of fatigue. Animals kept in the wet cage for 5 days showed a reduction in 2-[18F]fluoro-2-deoxy-D-glucose uptake into their brain. The session for 1 day showed significantly increased 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) and [3,4-dihydroxyphenyl-acetic acid (DOPAC)+homovanillic acid (HVA)]/dopamine (DA) ratios in all brain regions, but the session for 5 days showed the restoration of the 5-HIAA/5-HT ratio in the hippocampus and hypothalamus and in the (DOPAC+HVA)/DA ratio in the striatum and hypothalamus. Our data suggest that decreased glucose uptake and insufficient serotonin and dopamine turnover introduced by deprivation of rest were correlated with central fatigue.
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PMID:Establishment and assessment of a rat model of fatigue. 1462 9

We recently established an animal model of fatigue in which rats were kept in a cage filled with water to a height of 1.5 cm for 5 days. In this way, after the fatigue session, they were returned to their home cage. Rats resting for 15 min or 2 h showed reduced 2-[18F]fluoro-2-deoxy-D-glucose uptake in their brain. Rats resting for 1 h showed a significantly increased ratio of 5-hydroxyindoleacetic acid/5-hydroxytryptamine, an index of serotonin turnover, in the frontal cortex, hippocampus, and cerebellum, and the ratio of [3,4-dihydroxyphenylacetic acid+homovanillic acid]/dopamine, an index of dopamine turnover, tended to be increased as compared with the control. These data suggest that improvement of glucose uptake and increased serotonergic and dopaminergic neuronal activities are associated with recovery from central fatigue.
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PMID:Recovery from fatigue: changes in local brain 2-[18F]fluoro-2-deoxy-D-glucose utilization measured by autoradiography and in brain monoamine levels of rat. 1466 8

We investigated the role of beta 3 Gal-T5, a member of the beta 1,3galactosyltransferase (beta 1,3Gal-T) family, in cancer-associated glycosylation, focusing on the expression of sialyl-Lewis a (sLea, the epitope of CA19.9 antigen), poly N-acetyllactosamines, and sialyl-Lewis x (sLex) antigen. A clone permanently expressing an antisense fragment of beta 3Gal-T5 was obtained from the human pancreas adenocarcinoma cell line BxPC3 and characterized. Both beta 1,3Gal-T activity and sLea expression are dramatically impaired in the clone. Analysis of the oligosaccharides synthesized in cells metabolically labelled with tritiated galactose shows that a relevant amount of radioactivity is associated to large O-glycans. Endo-beta-galactosidase mostly releases NeuAc alpha 2-3Gal beta 1-3[Fuc alpha 1-4]GlcNAc beta 1-3Gal and NeuAc alpha 2-3Gal beta 1-3GlcNAc beta 1-3Gal from such O-glycans of BxPC3 membranes, but GlcNAc beta 1-3Gal and type 2 chain oligosaccharides, including NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc beta 1-3Gal, from those of the antisense clone. Furthermore, BxPC3 cells secrete sLea in the culture media but not sLex, while antisense clone secretes mostly sLex, and accumulation of both antigens is prevented by benzyl-alpha-GalNAc. These data indicate that beta 3Gal-T5 suppression turns synthesis of type 1 chain O-glycans to poly N-acetyllactosamine elongation and termination by sLex. In other cell lines and clones, beta 3Gal-T5 transcript, beta 1,3Gal-T activity, and sLea antigen are also correlated, but quantitatively the relative expression ratios are very different from cell type to cell type. We suggest that beta 3Gal-T5 plays a relevant role in gastrointestinal and pancreatic tissues counteracting the glycosylation pattern associated to malignancy, and is necessary for the synthesis and secretion of CA19.9 antigen, whose expression still depends on multiple interacting factors.
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PMID:Suppression of beta 1,3galactosyltransferase beta 3Gal-T5 in cancer cells reduces sialyl-Lewis a and enhances poly N-acetyllactosamines and sialyl-Lewis x on O-glycans. 1468 31

Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.
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PMID:Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy. 1504 96


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