Disease relevance of 1-Deoxymannojirimycin

• The effects of 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM), inhibitors of oligosaccharide trimming glucosidase I and mannosidase I, respectively, on the biosynthesis of vesicular stomatitis virus G protein, influenza virus hemagglutinin, and human class I histocompatibility antigens were investigated [1].
• Inhibition by tunicamycin (lipid-linked oligosaccharide precursor synthesis), castanospermine, 1-deoxynojirimycin, and 1-deoxymannojirimycin attenuated HIV-1 infectivity and blocked HIV-1-induced syncytium formation and cytopathicity, whereas bromoconduritol and swainsonine failed to have such effects [2].
• 1-Deoxymannojirimycin (dMM), a specific alpha-mannosidase I inhibitor, completely blocks the conversion of Man9-8GlcNAc2 into Man7-5-GlcNAc2 in both differentiated and undifferentiated human adenocarcinoma HT-29 cells [3].
• In contrast, parent lymphoma cells, as well as HepG2 cells in the presence of 1-deoxymannojirimycin accumulated Man9GlcNAc2 as the primary deglucosylated N-linked oligosaccharide and contained only about 16% of their Man8GlcNAc2 as isomer A [4].
• Although inhibition of glucosidase activity by 1- deoxynojirimycin caused a 10-fold drop in virion formation, transport of G protein to the plasma membrane was not altered [5].

High impact information on 1-Deoxymannojirimycin

• Altering the N-linked carbohydrates on stimulator cells by use of the N-linked trimming glycosidase inhibitors 1-deoxymannojirimycin and swainsonine, or by treatment with bacterial neuraminidase, results in a restoration of the B6 anti-bm6 response in the absence of CD4+ cells [6].
• Cruzipain, a lysosomal proteinase having three potential N-glycosylation sites, two at the catalytic domain and one at the COOH-terminal domain, was isolated in a glucosylated form from cells grown in the presence of the glucosidase II inhibitor 1-deoxynojirimycin [7].
• In spite of not affecting cell growth rate or the cellular general metabolism in short and long term incubations, 1-deoxynojirimycin caused a marked delay in the arrival of cruzipain to lysosomes [7].
• As judged by equilibrium gradient centrifugation, 1- deoxynojirimycin caused alpha 1-antitrypsin and alpha 1-antichymotrypsin to accumulate in the rough endoplasmic reticulum [8].
• 1- Deoxynojirimycin is a specific inhibitor of glucosidases I and II, the first enzymes that process N-linked oligosaccharides after their transfer to polypeptides in the rough endoplasmic reticulum [8].

Chemical compound and disease context of 1-Deoxymannojirimycin

• Dual effect of 1-deoxymannojirimycin on the mannose uptake and on the N-glycan processing of the human colon cancer cell line HT-29 [3].
• The alpha-glucosidase inhibitor 1-deoxynojirimycin blocks human immunodeficiency virus envelope glycoprotein-mediated membrane fusion at the CXCR4 binding step [9].
• The present study investigates the antiviral effects of the alpha-glucosidase and alpha-mannosidase inhibitors (castanospermine, 1-deoxynojirimycin, bromoconduritol, deoxymannojirimycin and swainsonine) on human parainfluenza virus type 3 (HPIV3) [10].
• The effect of a new alpha-glucosidase inhibitor (BAY m 1099), a 1-deoxynojirimycin derivative, was studied in 10 black patients with Type II diabetes mellitus [11].

Biological context of 1-Deoxymannojirimycin

• The glucosidase inhibitors nojirimycin (NM) and 1-deoxynojirimycin (dNM) interfere with N-linked glycosylation [12].
• Chemical modification of the glucosidase inhibitor 1-deoxynojirimycin. Structure-activity relationships [13].
• In pulse-chase experiments we compared the kinetics of early carbohydrate processing and subsequent secretion of thyroid-stimulating hormone (TSH) and free alpha subunit under control conditions and after treatment with 1-deoxynojirimycin, an inhibitor of glucosidases I and II [14].
• In order to determine the role of carbohydrate chain processing in insulin receptor biogenesis, we investigated the effect of inhibiting glucose removal from core oligosaccharides of the insulin proreceptor with glucosidase inhibitors, castanospermine and 1-deoxynojirimycin [15].
• The virus aggregation phenotype of NE2G216 was reproduced in vertebrate cells (Pro-5) by the addition of 1-deoxymannojirimycin, an inhibitor of carbohydrate processing which limits the processing of N-linked oligosaccharides to structures that are structurally similar, albeit not identical, to those synthesized in C6/36 cells [16].

Anatomical context of 1-Deoxymannojirimycin

• Cathepsin D and beta-hexosaminidase synthesized in the presence of 1-deoxynojirimycin accumulate in the endoplasmic reticulum [17].
• In the presence of 1-deoxymannojirimycin, a specific inhibitor of alpha-mannosidase I, differentiated HT-29 cells, as expected, accumulate Man9-8-GlcNAc2 species, whereas in undifferentiated HT-29 cells these compounds continue to be rapidly degraded [18].
• 1-deoxynojirimycin impairs oligosaccharide processing of alpha 1-proteinase inhibitor and inhibits its secretion in primary cultures of rat hepatocytes [19].
• When grown in the presence of 1-deoxymannojirimycin, the C5b-9-inhibitory activity of CD59 expressed on the surface of the transfected CHO cells was reduced by an amount comparable to that observed for the N-glycanase digested protein [20].
• 1-Deoxymannojirimycin, an inhibitor of Golgi alpha-mannosidase I, had no influence on the rate of appearance of these hydrolases in the brush border membrane as assessed by subcellular fractionation [21].

Associations of 1-Deoxymannojirimycin with other chemical compounds

• We have also examined the effects of DTT, tunicamycin, 1-deoxymannojirimycin, pilocarpine, and testosterone on PSA biosynthesis and secretion [22].
• Forms of alpha 1-AT identical to those retained with ionomycin or thapsigargin were observed upon treatment with the alpha-1,2-mannosidase inhibitor 1-deoxymannojirimycin whereas castanospermine, an inhibitor of ER alpha-glucosidase I, produced different forms of the glycoprotein [23].
• Both tunicamycin and 1-deoxynojirimycin inhibit exit from the endoplasmic reticulum in parallel with their effects on the acquisition of binding activity [24].
• The location of the conserved acidic residues of the catalytic site and the binding of the inhibitors, kifunensine and 1-deoxymannojirimycin, to the essential calcium ion are conserved in the fungal enzyme [25].
• The inhibition of maturation was at the stage of N-linked glycosylation in the Golgi, because the immature integrin subunits were sensitive to endoglycosidase H digestion and the inhibition could be mimicked in adherent cells by treatment with 1-deoxymannojirimycin [26].

Gene context of 1-Deoxymannojirimycin

• Treatment of B16F10 cells with 1-deoxymannojirimycin, which prevents N-glycan processing, restored the ability of SHPS-1 derived from these cells to bind CD47-Fc in vitro, indicating that aberrant N-glycosylation of SHPS-1 impairs CD47 binding in B16F10 cells [27].
• As expected, binding of TAA90K to galectin-3 was dependent on carbohydrate since it was inhibitable by lactose and asiolofetuin, and a TAA90K-His glycoform purified from HT-29 cells treated with the glycosylation inhibitor 1-deoxymannojirimycin bound poorly to galectin-3 [28].
• Differing conformations of 1-deoxymannojirimycin were also observed: a (4)C(1) and (1)C(4) conformation in dGMII and hERMI, respectively [29].
• To elucidate the role of N-linked glycans in triggering T-cell functions, the effects of the N-glycan processing inhibitors 1-deoxymannojirimycin (1-DMM) and swainsonine (SW) were investigated on signaling events and induction of apoptosis in galectin-1 (gal-1)-stimulated Jurkat T lymphocytes [30].
• Finally, when melanoma cells are treated with inhibitors of carbohydrate processing, such as N-methyl-1-deoxynojirimycin, 1-deoxymannojirimycin and swainsonine, they still secrete a motility-stimulating autotaxin [31].

Analytical, diagnostic and therapeutic context of 1-Deoxymannojirimycin

• In both the embryonic and cell culture systems 1-deoxymannojirimycin (1-MMN) and, to a lesser extent, 1-deoxynojirimycin (1-DNJ) inhibited spicule formation [32].
• Here, the binding of 1-deoxynojirimycin and (+)-isofagomine to the "family GH-1" beta-glucosidase of Thermotoga maritima is investigated by kinetic analysis, isothermal titration calorimetry, and X-ray crystallography [33].
• Iminosugar glycosidase inhibitors: structural and thermodynamic dissection of the binding of isofagomine and 1-deoxynojirimycin to beta-glucosidases [33].
• The inhibitor was localized by immunofluorescence in the wall of the 1-deoxynojirimycin-treated cells [34].
• Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversed-phase high-performance liquid chromatography [35].

References