Production of hybrid glycoproteins and accumulation of oligosaccharides in the brain of sheep and pigs administered swainsonine or locoweed.
Swainsonine and swainsonine-containing plants produce biochemical and neurological changes in several mammalian species. The toxin is a potent inhibitor of liver lysosomal alpha-D-mannosidase and Golgi mannosidase II. The inhibition of the latter enzyme causes the production of abnormal glycoproteins containing hybrid oligosaccharides instead of complex types in a variety of cultured cells. In view of the widespread occurrence and biological importance of N-linked glycoproteins in the central nervous system, we initiated studies to determine the structure of oligosaccharides in glycoproteins prepared from the brain of control, swainsonine-fed, and locoweed-fed animals. The results presented here indicate that the feeding led to alteration in the structure of brain glycoproteins. Over 25% of the glycoproteins which presumably contained complex-type oligosaccharides were modified and now contained hybrid oligosaccharides. The structure of the N-linked oligosaccharide (glycopeptide) was established by (a) studying the binding properties of the glycopeptide to immobilized lectins of known sugar specificity, and (b) comparing the size of the glycopeptide before and after treatment with exo- and endoglycosidases. The production of hybrid oligosaccharides occurred despite the apparent absence of mannosidase II in brain. The relationships of the altered structure of brain glycoproteins, accumulation of mannose-rich oligosaccharides in the brain, and abnormal behavior of the animals administered swainsonine or locoweed are discussed.
D000117:Acetylglucosamine / Q000032:analysis; D000118:Acetylglucosaminidase / Q000378:metabolism; D000470:Alkaloids / Q000494:pharmacology*; D000821:Animal Feed; D000818:Animals; D001216:Asparagine / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002417:Cattle; D002846:Chromatography, Affinity; D006023:Glycoproteins / Q000096:biosynthesis*; D006596:Hexosaminidases / Q000378:metabolism; D008358:Mannose / Q000032:analysis; D008361:Mannosidases / Q000378:metabolism; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase / Q000378:metabolism; D009844:Oligosaccharides / Q000032:analysis / Q000378:metabolism*; D010947:Plants, Toxic; D012756:Sheep; D012794:Sialic Acids / Q000032:analysis; D017026:Swainsonine; D013552:Swine; D001616:beta-Galactosidase / Q000378:metabolism
D000470:Alkaloids; D006023:Glycoproteins; D009844:Oligosaccharides; D012794:Sialic Acids; D001216:Asparagine; D006596:Hexosaminidases; D008361:Mannosidases; D009439:Neuraminidase; D001616:beta-Galactosidase; D000118:Acetylglucosaminidase; D019158:N-Acetylneuraminic Acid; D008358:Mannose; D017026:Swainsonine; D000117:Acetylglucosamine