Effects of 4-deoxy- l- threo-pentose, a novel carbohydrate, on neural cell proteoglycan synthesis and function

• Published in: Biochimica et biophysica acta Vol. 1156; no. 1; pp. 7 - 14
• Main Authors: Dow, Kimberly E., Riopelle, Richard J., Szarek, Walter A., Bols, Mikael, Ison, Edward R., Plenkiewicz, Jan, Lyon, Andrew, Kisilevsky, Robert
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 08.12.1992; Elsevier
• Subjects: Animals; Animals, Newborn; Astrocytes - drug effects; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Fundamental and applied biological sciences. Psychology; Glycosaminoglycan; Glycosaminoglycans - biosynthesis; Liver - drug effects; Liver - metabolism; Molecular and cellular biology; Neurite-promoting; Neurons - drug effects; Neurons - metabolism; Proteoglycan; Proteoglycans - biosynthesis; Rats; Xylose - analogs & derivatives; Xylose - chemical synthesis; Xylose - pharmacology; Proteoglycan; Neurite-promoting; Glycosaminoglycan; Cell culture; Vertebrata; Mammalia; Neuron; Rat; Structure activity relation; Rodentia; Glycoproteins; Astrocyte; Carbohydrate chain; Cell differentiation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/0304-4165(92)90088-C

A novel carbohydrate, 4-deoxy- l- threo-pentose (4-deoxyxylose), was synthesized by way of reductive dechlorination of a chlorodeoxy sugar. This carbohydrate, an analogue of xylose which is required for the initiation of glycosaminoglycan (GAG) synthesis, was used to explore the function of GAG side chains in neurite outgrowth on a laminin substrate. 4-Deoxyxylose inhibited the incorporation of 35SO 4 into the GAGs of neuronal and astrocytic proteoglycans, with no effect being seen on the incorporation of [ 3H]glucosamine into proteoglycan. Direct analysis of the heparan sulphate fraction from such cells using nitrous acid digestion confirmed that the GAGs were undersulphated. No inhibition of either 35SO 4 or [ 3H]glucosamine incorporation was observed in primary mouse hepatocytes exposed to 4-deoxyxylose. 4-Deoxyxylose produced a direct dose-dependent inhibition of neurite outgrowth by sensory neurons, and medium conditioned by neurons or astrocytes in the presence of 4-deoxyxylose displayed less laminin-complexed neurite-promoting activity than medium conditioned in its absence. These data suggest that 4-deoxyxylose inhibits neurite outgrowth by altering the sulphation of the GAGs of heparan sulphate proteoglycans.