Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1966 Nov 30;124(6):1181–1198. doi: 10.1084/jem.124.6.1181

HURLER'S SYNDROME

EFFECT OF RETINOL (VITAMIN A ALCOHOL) ON CELLULAR MUCOPOLYSACCHARIDES IN CULTURED HUMAN SKIN FIBROBLASTS

B Shannon Danes 1, Alexander G Bearn 1
PMCID: PMC2138335  PMID: 4224371

Abstract

Skin fibroblasts from eight families with Hurler's syndrome (X-linked recessive and autosomal recessive) and normal individuals have been studied in cell culture. A good correlation between cellular metachromasia and the quantitative estimation of intracellular mucopolysaccharides was observed provided the culture conditions were standardized. In both forms of Hurler's syndrome intracellular mucopolysaccharide content could be used to distinguish the affected individual and the carrier from the normal subject, although the total mucopolysaccharide content of fibroblast cultures or the amount in the culture medium did not permit such a distinction. Retinol, in concentrations similar to those encountered in man in hyper-vitaminosis A, caused a reduction in total mucopolysaccharide content of fibroblast cultures from normal and affected individuals. Cultures from three patients with the X-linked recessive form of Hurler's syndrome showed a gradual but marked decrease in cellular metachromasia and approximately 60% decrease in mucopolysaccharide content. Synthesis of polysaccharides and sulfation appeared to be equally affected. On removal of retinol from the medium the content of intracellular mucopolysaccharides returned to pretreatment levels. The possible relevance of these findings to the treatment of Hurler's syndrome is discussed.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BERENSON G. S., LUMPKIN W. M., SHIPP V. G. Study of the time-course production of acid mucopolysaccharides by fibroblasts in a synthetic medium. Anat Rec. 1958 Dec;132(4):585–596. doi: 10.1002/ar.1091320407. [DOI] [PubMed] [Google Scholar]
  2. BRANTE G. Gargoylism; a mucopolysaccharidosis. Scand J Clin Lab Invest. 1952;4(1):43–46. doi: 10.3109/00365515209060631. [DOI] [PubMed] [Google Scholar]
  3. DAVIDSON E. H. Heritability and control of differentiated function in cultured cells. J Gen Physiol. 1963 May;46:983–998. doi: 10.1085/jgp.46.5.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DINGLE J. T., LUCY J. A. Studies on the mode of action of excess of vitamin A. 5. The effect of vitamin A on the stability of the erythrocyte membrane. Biochem J. 1962 Sep;84:611–621. doi: 10.1042/bj0840611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DORFMAN A., SCHILLER S. Effects of hormones on the metabolism of acid mucopolysaccharides of connective tissue. Recent Prog Horm Res. 1958;14:427–456. [PubMed] [Google Scholar]
  6. Danes B. S., Bearn A. G. Hurler's syndrome. A genetic study in cell culture. J Exp Med. 1966 Jan 1;123(1):1–16. doi: 10.1084/jem.123.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dorfman A., Lorincz A. E. OCCURRENCE OF URINARY ACID MUCOPOLYSACCHARIDES IN THE HURLER SYNDROME. Proc Natl Acad Sci U S A. 1957 Jun 15;43(6):443–446. doi: 10.1073/pnas.43.6.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. EAGLE H. The minimum vitamin requirements of the L and HeLa cells in tissue culture, the production of specific vitamin deficiencies, and their cure. J Exp Med. 1955 Nov 1;102(5):595–600. doi: 10.1084/jem.102.5.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FELL H. B., DINGLE J. T. Studies on the mode of action of excess of vitamin A. 6. Lysosomal protease and the degradation of cartilage matrix. Biochem J. 1963 May;87:403–408. doi: 10.1042/bj0870403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FELL H. B., DINGLE J. T., WEBB M. Studies on the mode of action of excess of vitamin A. 4. The specificity of the effect on embryonic chick-limb cartilage in culture and on isolated rat-liver lysosomes. Biochem J. 1962 Apr;83:63–69. doi: 10.1042/bj0830063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FELL H. B., MELLANBY E., PELC S. R. Influence of excess vitamin A on the sulphate metabolism of bone rudiments grown in vitro. J Physiol. 1956 Oct 29;134(1):179–188. doi: 10.1113/jphysiol.1956.sp005633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. FELL H. B., MELLANBY E. The effect of hypervitaminosis A on embryonic limb bones cultivated in vitro. J Physiol. 1952 Mar;116(3):320–349. doi: 10.1113/jphysiol.1952.sp004708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. GRIBETZ D., SILVERMAN S. H., SOBEL A. E. Vitamin A poisoning. Pediatrics. 1951 Mar;7(3):372–385. [PubMed] [Google Scholar]
  14. GROSSFELD H., MEYER K., GODMAN G., LINKER A. Mucopolysaccharides produced in tissue culture. J Biophys Biochem Cytol. 1957 May 25;3(3):391–396. doi: 10.1083/jcb.3.3.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. MEYER K., GRUMBACH M. M., LINKER A., HOFFMAN P. Excretion of sulfated mucopolysaccharides in gargoylism (Hurler's syndrome). Proc Soc Exp Biol Med. 1958 Feb;97(2):275–279. doi: 10.3181/00379727-97-23714. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES