Open AccessStructural and functional consequences of increased tubulin glycosylation in diabetes mellitus.
Author(s) -
Stuart K. Williams,
Nancy L. Howarth,
James J. Devenny,
Mark W. Bitensky
Publication year - 1982
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.79.21.6546
Subject(s) - tubulin , glycosylation , gtp' , biochemistry , microtubule , diabetes mellitus , streptozotocin , chemistry , gel electrophoresis , polyacrylamide gel electrophoresis , biology , microbiology and biotechnology , endocrinology , enzyme
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.