muramidase and Lipidoses

The present study was undertaken to clarify whether or not chlorphentermine-induced lipidosis in the proximal tubules of the rat kidney interferes with lysosomal degradation of an absorbed exogenous protein. 125I-lysozyme was injected in vivo; its degradation was measured in vitro using slices from renal cortex. The subcellular distribution of the protein was examined by electron microscope autoradiography. Lysosomes structurally altered by the lipidosis were able to accumulate the protein, although to a smaller extent than normal-appearing lysosomes present in the same cells; the label persisted longer in the altered than in the normal-appearing lysosomes. Protein degradation was significantly decreased in renal cortical slices from chlorphentermine-treated rats compared with controls. The results indicate that experimentally-induced lipidosis is associated with decreased proteolytic efficiency of the lysosomes in proximal tubules.

Topics: Animals; Autoradiography; Chlorphentermine; Iodine Radioisotopes; Kidney Tubules, Proximal; Lipidoses; Lysosomes; Male; Microscopy, Electron; Muramidase; Rats; Rats, Inbred Strains

To correct a genetic defect, it would not be enough, say, to inject the missing enzyme, since the body's immune defenses would rapidly destroy it. A "Trojan horse" is needed to evade immune surveillance. The evolution of such an approach is described, as well as how it has been used to "cure" Tay-Sachs disease in culture, utilizing immunoglobulin-disguised liposomes to bring hexosaminidase A to deficient cells.

Topics: Animals; Cells, Cultured; Cytoplasm; Disease Models, Animal; Enzyme Therapy; Genetic Engineering; Hexosaminidases; Humans; Immunoglobulins; Leukocytes; Lipidoses; Liposomes; Lysosomes; Metabolism, Inborn Errors; Muramidase; Peroxidases; Phagocytes; Sharks

Topics: Erythrocytes; Glycolipids; Glycosaminoglycans; Glycosphingolipids; Granulocytes; Humans; Lipid Metabolism; Lipidoses; Lymphocytes; Macrophages; Metabolic Diseases; Mucopolysaccharidoses; Muramidase; Oligosaccharides; Phagocytosis; Phospholipids

Antisera were raised to preparations of hexosaminidase isoenzymes A and B purified from human liver. Protein that cross-reacted with the liver hexosaminidase was detected by an antibody-consumption method. A cross-reacting protein with a low molecular weight (20000) was partially characterized and purified from control human liver. This protein is also present in the liver of patients with Tay-Sachs disease or with Sandhoff's disease. Hexosaminidases A and B gave an immunological reaction of partial identity with the low-molecular-weight protein. The possible identity of the low-molecular-weight cross-reacting protein as a subunit of hexosaminidase is discussed.

Topics: Acetamides; Animals; Antigen-Antibody Reactions; Chromatography, DEAE-Cellulose; Chromatography, Gel; Chromatography, Ion Exchange; Cross Reactions; Electrophoresis, Disc; Glucosidases; Hexosaminidases; Humans; Immune Sera; Immunodiffusion; Isoenzymes; Lipidoses; Liver; Molecular Weight; Muramidase; Rabbits

Topics: Autopsy; Brain; Cornea; Diagnosis, Differential; Eye Manifestations; Female; Fibroblasts; Galactosidases; Glucuronidase; Glycosaminoglycans; Glycoside Hydrolases; Hexosaminidases; Histocytochemistry; Humans; Infant; Keratins; Lipidoses; Lysosomes; Microscopy, Electron; Mononuclear Phagocyte System; Muramidase; Phospholipids; Retina; Sulfatases