concanavalin-a and Tay-Sachs-Disease

concanavalin-a has been researched along with Tay-Sachs-Disease* in 4 studies

Other Studies

4 other study(ies) available for concanavalin-a and Tay-Sachs-Disease

ArticleYear
Comparative kinetics of phosphomannosyl receptor-mediated pinocytosis of fibroblast secretion acid hydrolases and glycopeptides prepared from them.
    Journal of cellular biochemistry, 1983, Volume: 22, Issue:2

    In a previous report we demonstrated that phosphorylated oligosaccharides isolated from acid hydrolases were subject to pinocytosis by phosphomannosyl receptors present on the cell surface of human fibroblasts [9]. However, limiting quantities of oligosaccharides precluded detailed comparison of the kinetics of pinocytosis of these phosphorylated oligosaccharides to those of the acid hydrolases from which they were derived. In this report we present studies comparing the kinetics of pinocytosis of acid hydrolases from NH4Cl-induced fibroblast secretions with those of concanavalin A-binding glycopeptides prepared from them by pronase digestion. The uptake of both secretion acid hydrolases and 125I-labeled glycopeptides was linear for at least 3 hr, saturable, inhibited competitively by mannose 6-phosphate, and destroyed by prior treatment of the ligand with alkaline phosphatase. The inhibition constants of excess unlabeled glycopeptide for the uptake of 125I-labeled glycopeptides (Ki of 1.5 X 10(-6) M) and for the uptake of secretion acid hydrolases (Ki of 2.2 X 10(-6) M) were remarkably similar. Furthermore, the Ki for mannose 6-phosphate inhibition of pinocytosis of glycopeptide uptake (3 X 10(-5) M) compares closely to that previously determined for the pinocytosis of intact "high-uptake" acid hydrolases (3-6 X 10(-5) M). "High-uptake" fractions of both ligands were prepared and quantified by affinity chromatography on immobilized phosphomannosyl receptors purified from bovine liver. Only 10% of the concanavalin A-binding glycopeptides bound to the immobilized phosphomannosyl receptors, while 80% of the acid hydrolases from which they were prepared bound and were eluted with 10 mM mannose 6-phosphate. However, the fraction of each type of ligand that binds to the immobilized phosphomannosyl receptors accounts for all the uptake activity of that ligand.

    Topics: Ammonium Chloride; beta-N-Acetylhexosaminidases; Chromatography, Affinity; Concanavalin A; Fibroblasts; Glycopeptides; Hexosaminidases; Humans; Hydrolases; In Vitro Techniques; Kinetics; Mannosephosphates; Pinocytosis; Receptor, IGF Type 2; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Tay-Sachs Disease

1983
Long-term intracellular retention of hexosaminidase A by Tay-Sachs disease brain and lung cells in vitro.
    Journal of neuroscience research, 1981, Volume: 6, Issue:3

    Enzyme-replacement treatment for metabolic storage disorders has been widely studied using model cell culture systems. This study determines the long-term fate of human hexosaminidase A supplied to Tay-Sachs disease brain and lung cells. Hex A retention studies showed that the incorporated Hex A is retained in undiminished quantity by TSD lung cells maintained in stationary culture for 14 days. Tay-Sachs disease brain cells similarly followed for 28 days in stationary culture showed an initial reduction in Hex A for 3 days, after which the Hex A level stabilized and remained relatively constant for the next 25 days. Hexosaminidase B isoenzyme was found to accumulate in both cell lines during extended cultivation, despite the observation that significant amounts were excreted into the extracellular environment. The demonstration of long-term intracellular retention of exogenously supplied therapeutic enzyme by the target cells offers additional evidence for the feasibility of an enzyme-replacement approach for study and treatment of lysosomal storage disorders.

    Topics: beta-N-Acetylhexosaminidases; Brain; Cells, Cultured; Concanavalin A; Hexosaminidase A; Hexosaminidase B; Hexosaminidases; Humans; In Vitro Techniques; Lung; Tay-Sachs Disease; Time Factors

1981
Enzyme replacement treatment for Tay-Sachs disease brain cells in culture utilizing concanavalin A-mediated hexosaminidase A uptake: biochemical and morphological evidence of GM2 mobilization.
    Acta neuropathologica, 1980, Volume: 50, Issue:1

    When Concanavalin A (Con A) is bound to the cell membrane, it functions as an artificial enzyme receptor, mediating the binding and intracellular incorporation of significant amounts of exogenous hexosaminidase A (Hex A) into Tay-Sachs disease (TSD) glia cells. The treated cells retained almost 50% of incorporated Hex A activity after 3 days incubation in Hex A free medium. Hex A was released from Con A within the cell and was available as free enzyme. Biochemical analysis of gangliosides in Con A and Hex A treated cells depicted a greater than 50% reduction in stored GM2 ganglioside and a fourfold reduction in GM2 label (14C) when compared to controls. Ultrastructural evidence of GM2 breakdown is presented which supports the biochemical and labeling studies.

    Topics: Cell Membrane; Cells, Cultured; Concanavalin A; G(M2) Ganglioside; Hexosaminidases; Humans; Neuroglia; Protein Binding; Tay-Sachs Disease

1980
Tay-Sachs disease brain cells in culture: mobilization of stored GM2 after concanavalin A-mediated uptake of hexosaminidase A.
    Journal of neuroscience research, 1980, Volume: 5, Issue:5

    A human Tay-Sachs disease (TSD) fetal-brain-cell line is a useful model for the disease since the cells lack hexosaminidase A and accumulate the ganglioside, GM2. This brain-cell line was used to assess the effect of hexosaminidase A treatment on GM2 storage material. Entry of placental hexosaminidase A into the cells was obtained by pretreatment of the cultures with concanavalin A. Cells were analyzed periodically during six days. During the course of the experiment, GM2 in the cells decreased by approximately 50%. A substantial amount of hexosaminidase A was maintained in the cultures throughuot the experiment. This strategy was successful in mobilizing stored GM2 in TSD brain-cell cultures. Therefore, the activating factor needed for hexosaminidas A activity must be present in TSD-cultured brain cells.

    Topics: Cell Line; Cerebellum; Concanavalin A; Enzyme Activation; G(M2) Ganglioside; Gangliosides; Hexosaminidases; Humans; Tay-Sachs Disease

1980