Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 79 ·No. 21 ·1982-11-00 ·Pages 6546-50

Williams SK, Howarth NL, Devenny JJ, Bitensky MW

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

Animals Brain/metabolism Chemical Phenomena Chemistry Colchicine/pharmacology Diabetes Mellitus/metabolism Glucose Glycoproteins/metabolism Male Microtubules/metabolism Protein Binding Rats Structure-Activity Relationship Tubulin/metabolism Vinblastine/pharmacology

Chemicals

Glycoproteins Tubulin Vinblastine Glucose Colchicine

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Williams S K

Howarth N L

Devenny J J

Bitensky M W

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28 references, click to expand

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.79.21.6546

Published

1982-11-00

Pages

6546-50

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC347164

Subset

External Links

PubMed source DOI: 10.1073/pnas.79.21.6546 PMC Full Text View journal details

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Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus.

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