title: Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus.
abstract: The extent of in vitro nonenzymatic glycosylation of purified rat brain tubulin was dependent on time and glucose concentration. Tubulin glycosylation profoundly inhibited GTP-dependent tubulin polymerization. Electron microscopy and NaDodSO4/polyacrylamide gel electrophoresis showed that glycosylated tubulin forms high molecular weight amorphous aggregates that are not disrupted by detergents or reducing agents. The amount of covalently bound NaB3H4-reducible sugars in tubulin recovered from brain of streptozotocin-induced diabetic rats was dramatically increased as compared with tubulin recovered from normal rat brain. Moreover, tubulin recovered from diabetic rat brain exhibited less GTP-induced polymerization than tubulin from nondiabetic controls. The possible implications of these data for diabetic neuropathy are discussed.
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D003078:Colchicine / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D005947:Glucose; D006023:Glycoproteins / Q000378:metabolism*; D008297:Male; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D014404:Tubulin; D014747:Vinblastine; D005947:Glucose; D003078:Colchicine