Skip to main content
SpringerLink
Log in

Inhibitors of cholesterol synthesis and myelin formation

  • Published:
Lipids

Abstract

Inhibitors of cholesterol biosynthesis AY 9944 and 20,25 diazacholesterol were administered by stomach tube to suckling rats in varying doses during the time of rapid myelination (15–22 days of age). Purified myelin was prepared from the brains and spinal cords, and the sterol content analyzed. Up to 50% of the myelin sterol consisted of desmosterol in rats treated with 20,25 diazacholesterol, while 7-dehydrocholesterol comprised at least one third of the myelin sterol in rats administered AY 9944. Myelin from rats treated with both compounds contained desmosterol, 7-dehydrocholesterol, Δ5,7,24 cholestatriene-3-β-ol and an unknown sterol, the four comprising about 45% of the total sterol. The proportion of phospholipid: galactolipid-total sterol in myelin from the drug-treated rats was not significantly different from the normal, although much less myelin was recovered. Brain and spinal cord slices from 22 to 25-day rats pretreated with inhibitors showed decreased uptake of U-14C-glucose into all myelin components. The decreased uptake was approximately proportional in all lipids and the protein was also affected. It is proposed that myelin composition is fixed, and that a deficiency of one of the lipid components will limit the assembly of the whole lipid portion of the membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Smith, M. E., Adv. Lipid Res. 5:241 (1967).

    PubMed  CAS  Google Scholar 

  2. Norton, W. T., S. E. Podulso and K. Suzuki, J. Neuropathol. Exptl. Neurol. 25:582 (1966).

    Article  CAS  Google Scholar 

  3. Norton, W. T., and S. Podulso, in “Variation in the Chemical Composition of the Nervous System,” Edited by G. B. Ansell, Oxford, Pergamon, 1966, p. 82.

    Google Scholar 

  4. Cumings, J. N., E. J. Thompson and H. Goodwin, J. Neurochem. 15:243 (1968).

    Article  PubMed  CAS  Google Scholar 

  5. Finean, J. B., Experientia 9:17 (1953).

    Article  PubMed  CAS  Google Scholar 

  6. Vandenheuvel, F. A., JAOCS 40:455 (1963).

    Google Scholar 

  7. Eng, L. F., and M. E. Smith, Lipids 1:296 (1966).

    CAS  PubMed  Google Scholar 

  8. Fumagalli, R., M. E. Smith, G. Urna and R. Paoletti, J. Neurochem. 16:1329 (1969).

    Article  PubMed  CAS  Google Scholar 

  9. Smith, M. E., Biochim. Biophys. Acta 164:285 (1968).

    PubMed  CAS  Google Scholar 

  10. Smith, M. E., J. Neurochem. 16:83 (1969).

    Article  PubMed  CAS  Google Scholar 

  11. Galli, G., and S. Maroni, Steroids 10:189 (1967).

    Article  PubMed  CAS  Google Scholar 

  12. Smith, M. E., R. Fumagalli and R. Paoletti, Life Sci. 6:1085 (1967).

    Article  PubMed  CAS  Google Scholar 

  13. Thompson, M. J., J. Dupont and W. E. Robbins, Steroids 2:99 (1963).

    Article  CAS  Google Scholar 

  14. Fumagalli, R., and R. Niemiro, Life Sci. 3:555 (1964).

    Article  PubMed  CAS  Google Scholar 

  15. Dvornik, D., M. Kraml, J. Dubuc, M. Givner and R. Gaudry, J. Amer. Chem. Soc. 85:3309 (1963).

    Article  CAS  Google Scholar 

  16. Kraml, M., J. F. Bagli and D. Dvornik, Biochem. Biophys. Res. Commun. 15:455 (1964).

    Article  PubMed  CAS  Google Scholar 

  17. Johnston, J. D., and K. Bloch, J. Amer. Chem. Soc. 79:1145 (1957).

    Article  CAS  Google Scholar 

  18. Fumagalli, R., R. Niemiro and R. Paoletti, JAOCS 42:1018 (1965).

    PubMed  CAS  Google Scholar 

  19. Scallen, T. J., W. J. Dean, E. D. Loughran and B. V. Vora, J. Lipid Res. 10:121 (1969).

    PubMed  CAS  Google Scholar 

  20. Demel, R. A., L. L. M. van Deenen and B. A. Pethica, Biochim. Biophys. Acta 135:11 (1967).

    Article  CAS  Google Scholar 

  21. DeGier, J., J. G. Mandersloot and L. L. M. van Deenen, Ibid. 173:143 (1969).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Veterans Administration Hospital, 94304, Palo Alto, California

    Marion Edmonds Smith & Catherine M. Hasinoff

  2. the Department of Neurology, Stanford University School of Medicine, Stanford, USA

    Marion Edmonds Smith & Catherine M. Hasinoff

  3. The Institute of Pharmacology, University of Milan, Italy

    Remo Fumagalli

Authors
  1. Marion Edmonds Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Catherine M. Hasinoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Remo Fumagalli
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Smith, M.E., Hasinoff, C.M. & Fumagalli, R. Inhibitors of cholesterol synthesis and myelin formation. Lipids 5, 665–671 (1970). https://doi.org/10.1007/BF02531432

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02531432

Keywords

Search

Navigation