Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus (original) (raw)

Summary

Diabetic neuropathy is associated with some early defects of axonal transport in experimental animals. Axonal transport is dependent on intact microtubules, and unsubstituted lysine residues of tubulin are essential for microtubule polymerization. As lysine residues are the major target for the non-enzymatic attachment of glucose, the effect of diabetes on the extent of glycation of tubulin was investigated. There was a more than four-fold increase in the extent of glycation of tubulin in the sciatic nerve of rats with streptozotocin-induced diabetes of 2 weeks duration compared with control rats. In contrast, no such increase in glycation was observed in brain microtubule protein from diabetic rats at that stage of diabetes. Incubation of brain microtubule protein with glucose prior to in vitro polymerization showed that the early stages of glycation were not associated with inhibition of microtubule assembly. The observed glycation of peripheral nerve tubulin in early experimental diabetes may nevertheless contribute to axonal transport abnormalities through an as yet undetermined impairment of microtubule function.

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References

  1. Vlassara H, Brownlee M, Cerami A (1981) Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus. Proc Natl Acad Sci USA 78: 5190–5192
    PubMed Google Scholar
  2. Sidenius P, Jakobsen J (1979) Axonal transport in early experimental diabetes. Brain Res 173: 315–330
    Article PubMed Google Scholar
  3. McLean WG, Frizell M, Sjöstrand J (1985) Pathology of axonal transport. In: Lajtha A (ed) Handbook of neurochemistry, Vol. 9. Plenum, New York, pp 67–86
    Google Scholar
  4. Schnapp BJ, Vale RD, Sheetz MP, Reese TS (1985) Single microtubules from squid axoplasm support bidirectional movement of organelles. Cell 40: 455–462
    Article PubMed Google Scholar
  5. Hoffmann PN, Lasek R (1975) The slow component of axonal transport. Identification of major structural polypeptides of the axon and their generality among mammalian neurons. J Cell Biol 66: 351–366
    PubMed Google Scholar
  6. Williams SK, Howarth NL, Devenny JJ, Bitensky MW (1982) Structural and functional consequences of increased tubulin glycosylation in diabetes mellitus. Proc Natl Acad Sci USA 79: 6546–6550
    PubMed Google Scholar
  7. O'Farrell PH (1975) High resolution two-dimensional electrophoresis of proteins. J Biol Chem 250: 4007–4021
    PubMed Google Scholar
  8. McLean WG (1985) Axonal transport of actin and regeneration rate in non-myelinated sensory nerve fibres. Brain Res 333: 225–260
    Google Scholar
  9. Friedman M (1982) Chemically reactive and unreactive lysine as an index of browning. Diabetes 31 [Suppl. 3]: 5–14
    Google Scholar
  10. Mellado W, Slebe JC, Maccioni RB (1982) Tubulin carbamoylation. Functional amino groups in microtubule assembly. Biochem J 203: 675–681
    PubMed Google Scholar
  11. Szasz J, Burn R, Sternlicht H (1982) Effect of reductive methylation on microtubule assembly. J Biol Chem 257: 3697–3704
    PubMed Google Scholar
  12. Abbate SL, Atkinson MB, Breuer AC (1991) Amount and speed of fast axonal transport in diabetes. Diabetes 40: 111–117
    PubMed Google Scholar
  13. Medori R, Autilio-Gambetti L, Monaco S, Gambetti P (1985) Experimental diabetic neuropathy: impairment of slow axonal transport with changes in axon cross-sectional area. Proc Natl Acad Sci USA 82: 7716–7720
    PubMed Google Scholar

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Authors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK
    N. A. Cullum, J. Mahon, K. Stringer & W. G. McLean

Authors

  1. N. A. Cullum
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  2. J. Mahon
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  3. K. Stringer
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  4. W. G. McLean
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Cullum, N.A., Mahon, J., Stringer, K. et al. Glycation of rat sciatic nerve tubulin in experimental diabetes mellitus.Diabetologia 34, 387–389 (1991). https://doi.org/10.1007/BF00403175

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