Disease relevance of AHSG

• While Diplococcus pneumoniae endo-alpha-DN-acetylgalactosaminidase acting on asialofetuin released the sialic acid-free tetra- and trisaccharides (Gal beta 1----3GalNAc), this enzyme did not cleave the peptide attachment of the asialohexasaccharide (Gal beta 1----3 [Gal beta 1----4GlcNAc beta 1----6] GalNAc) [1].
• That these peptides are of functional significance is evidenced by the ability of both P30 and P10 to inhibit asialofetuin-mediated melanoma cell aggregation in vitro and to compete with peanut lectin for binding to T antigen displayed on the surface of MDA-MB-435 breast carcinoma cells in situ [2].
• Interaction of HIV-1 rgp120 subunit with the two affinity matrices was also inhibited by M6P, but only rgp120 binding to heparin-agarose, and not that to SDB, was affected by fetuin and asialofetuin [3].
• Administration of fetuin (5-500 mg/kg intraperitoneally) dose-dependently attenuated the development of paw edema as compared to either asialofetuin (500 mg/kg) or bovine albumin (500 mg/kg) [4].
• Since the transglycosylation product, beta-D-Gal-(1-->3)-alpha-D-GalNAc-(1-->O)-hexyl, efficiently inhibits the binding of anti-T antigen monoclonal antibody to asialofetuin, it has potential as an agent for blocking T antigen-mediated cancer metastasis [5].

High impact information on AHSG

• Conjugates of asialofetuin bound to folic acid (folate derivative requiring dihydrofolate reductase activity for conversion to an active metabolite) and fetuin (non-galactose-terminal glycoprotein) linked to folinic acid also were made for control studies [6].
• Very similar results were obtained when asialofetuin and antifreeze glycoprotein were used as an acceptor [7].
• Extracts of cultured 3T3 fibroblasts, obtained by homogenization and Triton X-100 solubilization, were fractionated on Sepharose columns covalently derivatized with asialofetuin [8].
• The synthetic peptides exhibited high specificities and affinities to T antigen displayed on asialofetuin or conjugated to bovine serum albumin (Kd = 5 nM for MAP-P30 binding to asialofetuin) as well as free T-antigen disaccharide in solution (Kd = 10 microM for MAP-P30, 20 microM for P10) [2].
• Finally, we demonstrate that fetuin-A binds to annexin II at the cell membrane of BVSMC [9].

Chemical compound and disease context of AHSG

• Binding of rgp140 and of corresponding rgp160 of HIV-1 to heparin- and DS-substituted (sulphated dextran beads; SDB) affinity matrices was inhibited by the soluble specific ligand and also by fetuin, asialofetuin or the anionic simple carbohydrate derivative mannose-6-phosphate (M6P) [3].
• Phagocytosis of Staphylococcus aureus by human peripheral polymorphonuclear leucocytes in vitro in the presence of fetal calf serum was inhibited by D-galactose, N-acetyl-D-glucosamine and asialofetuin but not by fetuin [10].

Biological context of AHSG

• The association kinetics of Asn-linked glycopeptides from bovine asialofetuin to recombinant macrophage lectin was determined by surface plasmon resonance spectroscopy [11].
• Unlabelled rABP and human sex steroid-binding protein (hSBP), but not lactotransferrin, serotransferrin, asialofetuin, fetuin or bovine serum albumin, competed with labelled rABP for binding sites on isolated germ cells [12].
• The alpha 2-HS-glycoprotein was the dominant bone NCP at 2 months in utero and then diminished with advancing fetal age [13].
• Bovine fetuin and human alpha(2)-HS glycoprotein significantly augmented the phagocytosis of apoptotic cells by human peripheral blood monocyte-derived macrophages, whereas the control proteins BSA, sialylated BSA and asialofetuin were ineffective [14].
• Anti-TF1 antibodies could be inhibited in the hemagglutination inhibition assay by asialofetuin, asialotransferrin, asialoglycophorin and asialomucin [15].

Anatomical context of AHSG

• Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins [9].
• Additional studies demonstrated the calcium-dependent uptake was specific for fetuin-A and only observed in BVSMC and osteoblasts, but not epithelial, endothelial, or adipose cells [9].
• MION-ASF is cleared from the circulation more than 300 times faster than MION, has a 3.7 times higher hepatic accumulation, increases liver R2 relaxivity 2.8-fold compared to MION, and accumulates in hepatocytes unlike MION, which accumulates only in macrophages [16].
• A significantly greater number of capacitated acrosome-intact spermatozoa bound to the beads coated with functional ngps than the beads coated with non-functional ngps, BSA, OVA, or ASF [17].
• These results suggest that the endocytosis of formaldehyde-treated bovine serum albumin in endothelial cells is maintained until the advanced stage of biliary obstruction, whereas the endocytic activity for asialofetuin in hepatocytes is impaired earlier [18].

Associations of AHSG with chemical compounds

• Cross-linking activity of the 14-kilodalton beta-galactoside-specific vertebrate lectin with asialofetuin: comparison with several galactose-specific plant lectins [19].
• Enzyme II appeared to be homogeneous in charge, in contrast to the heterogeneity observed for enzyme I. Studies on their specificity using natural substrates showed that enzyme I hydrolyzed GM1, asialofetuin and lactose [20].
• Conversely, 3LL cells in s.c. tumors bound heparin and asialofetuin to greater extents than cancer cells in kidney tumors [21].
• A portion of the labeling, representing 40-60% of the total, was sensitive to reagents which were known to inhibit carbohydrate binding by discoidin I, including GalNAc, asialofetuin, and ethylenediaminetetraacetic acid [22].
• The explants were incubated (39 degrees C, 5% CO2) with fetuin, asialofetuin, ovalbumin, fucoidan, fucose, N-acetyl glucosamine, or N-acetyl glucosamine sulfate dissolved in a modified Tyrode's balanced salt solution, termed sperm-TALP (pH 7.4, 295 mOsm) for 10 min before frozen-thawed motile sperm obtained by swim-up were added [23].

Other interactions of AHSG

• Adherence was saturable, time and dose dependent, and selectively blocked by glycoconjugates, in particular bovine submaxillary mucin, fetuin, and asialofetuin, suggesting that it may be mediated by a lectin type of interaction [24].
• The plasma proteins found in bone include, but are not limited to albumin, apo A-I lipoprotein, IgG, IgM, transferrin, alpha-2-HS-glycoprotein, and hemoglobin [25].
• The serum proteins alpha-2 HS glycoprotein, gamma-globulin and fetuin, and the proline-rich salivary protein termed P-B were also identified in the enamelin extract [26].
• Treatment of asialofetuin with endo--alpha--N--acetylgalactosaminidase eliminated its affinity for the lectin column, and other proteins known to contain only N-linked oligosaccharides such as ovalbumin, transferrin, and alpha 1-acid glycoprotein were not retained by the lectin [27].
• P. carinii erythrocyte-adherence was best inhibited by bovine submaxillary mucin and by a polysaccharide from the wall of group A Streptococcus, and to a lesser extent by Streptococcus group C polysaccharide, asialofetuin and fetuin [28].

Analytical, diagnostic and therapeutic context of AHSG

• To examine the mechanism by which fetuin-A is taken up in bovine VSMC (BVSMC), we examined living cells by confocal microscopy and determined the uptake of Cy5-labeled fetuin-A [9].
• Furthermore, rosette formation could be completely blocked in the presence of excess asialofetuin or D-galactose, while excess ovalbumin or D-mannose had no effect [29].
• To help understand the mechanics and kinetics of dissociation of receptor-ligand complexes, we have analyzed the separation of lactose and the N-glycan chains of asialofetuin (ASF) from three lectins and an immunoglobulin G fraction by surface plasmon resonance at zero force and by atomic force microscopy with variations of the external force [30].
• In contrast to fBSA, the endocytotic index in hepatocytes evaluated with 125I-labeled asialofetuin reached the minimum level on the second day, and then recovered to the control level 10 days after hepatectomy [31].
• We measured the affinity of more than 20 sugars with concanavalin A (ConA) by an optical biosensor (surface plasmon resonance sensor) using asialofetuin (ASF) as an immobilized binding partner of ConA [32].

References