Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus.
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.
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
D006023:Glycoproteins; D014404:Tubulin; D014747:Vinblastine; D005947:Glucose; D003078:Colchicine