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 glycosylat...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1982-11, Vol.79 (21), p.6546-6550
Main Authors: Williams, Stuart K., Howarth, Nancy L., Devenny, James J., Bitensky, Mark W.
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Chemical Phenomena
Chemistry
Colchicine - pharmacology
Diabetes
Diabetes complications
Diabetes mellitus
Diabetes Mellitus - metabolism
Diabetic neuropathies
Gels
Glucose
Glycoproteins - metabolism
Homogenization
Male
Microtubules
Microtubules - metabolism
Molecular weight
Monomers
Polymerization
Protein Binding
Rats
Structure-Activity Relationship
Tubulin - metabolism
Vinblastine - pharmacology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.79.21.6546