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. 1980 Nov 15;192(2):579–586. doi: 10.1042/bj1920579

Reduced lysyl oxidase activity in skin fibroblasts from patients with Menkes' syndrome.

P M Royce, J Camakaris, D M Danks
PMCID: PMC1162373  PMID: 6112984

Abstract

Lysyl oxidase activity against both collagen and elastin substrates has been examined in the culture medium of skin fibroblasts derived from unrelated patients with Menkes' syndrome and from control subjects. The medium of three Menkes' fibroblast lines showed 3--30% of the activity present in the medium of control fibroblasts, against a purified collagen substrate. Lysyl oxidase activity in the culture medium of two of the Menkes' fibroblast lines was also examined by using a crude aortic-elastin substrate and was similarly decreased in comparison with that in the medium of control fibroblasts. Lysyl oxidase activity in the medium of a fourth fibroblast line, derived from a foetus with Menkes' syndrome, was 42% of that in the medium of control fibroblasts derived from a 1-day-old baby against a collagen substrate, and 26% of that in control fibroblast medium against an elastin substrate. The copper content of the cell layers of the Menkes' fibroblast cultures was elevated in comparison with normal fibroblast cultures, as has previously been reported to be characteristic of such cells. It is suggested that the decrease in lysyl oxidase activity would help to explain the connective tissue defects observed in Menkes' syndrome, and that this reduction, in conjunction with the elevated concentrations of cellular copper, would support the hypothesis that a functional intracellular copper deficiency exists in Menkes' syndrome.

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Selected References

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

  1. Bailey A. J., Robins S. P., Balian G. Biological significance of the intermolecular crosslinks of collagen. Nature. 1974 Sep 13;251(5471):105–109. doi: 10.1038/251105a0. [DOI] [PubMed] [Google Scholar]
  2. Camakaris J., Danks D. M., Ackland L., Cartwright E., Borger P., Cotton R. G. Altered copper metabolism in cultured cells from human Menkes' syndrome and mottled mouse mutants. Biochem Genet. 1980 Feb;18(1-2):117–131. doi: 10.1007/BF00504364. [DOI] [PubMed] [Google Scholar]
  3. Carnes W. H. Role of copper in connective tissue metabolism. Fed Proc. 1971 May-Jun;30(3):995–1000. [PubMed] [Google Scholar]
  4. Daish P., Wheeler E. M., Roberts P. F., Jones R. D. Menkes's syndrome. Report of a patient treated from 21 days of age with parenteral copper. Arch Dis Child. 1978 Dec;53(12):956–958. doi: 10.1136/adc.53.12.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Danks D. M., Campbell P. E., Stevens B. J., Mayne V., Cartwright E. Menkes's kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics. 1972 Aug;50(2):188–201. [PubMed] [Google Scholar]
  6. Danks D. M., Campbell P. E., Walker-Smith J., Stevens B. J., Gillespie J. M., Blomfield J., Turner B. Menkes' kinky-hair syndrome. Lancet. 1972 May 20;1(7760):1100–1102. doi: 10.1016/s0140-6736(72)91433-x. [DOI] [PubMed] [Google Scholar]
  7. Danks D. M., Cartwright E., Stevens B. J., Townley R. R. Menkes' kinky hair disease: further definition of the defect in copper transport. Science. 1973 Mar 16;179(4078):1140–1142. doi: 10.1126/science.179.4078.1140. [DOI] [PubMed] [Google Scholar]
  8. Di Ferrante N., Leachman R. D., Angelini P., Donnelly P. V., Francis G., Almazan A. Lysyl oxidase deficiency in Ehlers-Danlos syndrome type V. Connect Tissue Res. 1975;3(1):49–53. doi: 10.3109/03008207509152341. [DOI] [PubMed] [Google Scholar]
  9. EAGLE H. Nutrition needs of mammalian cells in tissue culture. Science. 1955 Sep 16;122(3168):501–514. doi: 10.1126/science.122.3168.501. [DOI] [PubMed] [Google Scholar]
  10. Goka T. J., Stevenson R. E., Hefferan P. M., Howell R. R. Menkes disease: a biochemical abnormality in cultured human fibroblasts. Proc Natl Acad Sci U S A. 1976 Feb;73(2):604–606. doi: 10.1073/pnas.73.2.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Harris E. D., Gonnerman W. A., Savage J. E., O'Dell B. L. Connective tissue amine oxidase. II. Purification and partial characterization of lysyl oxidase from chick aorta. Biochim Biophys Acta. 1974 Apr 25;341(2):332–344. doi: 10.1016/0005-2744(74)90226-5. [DOI] [PubMed] [Google Scholar]
  12. Hess H. H., Lees M. B., Derr J. E. A linear Lowry--Folin assay for both water-soluble and sodium dodecyl sulfate-solubilized proteins. Anal Biochem. 1978 Mar;85(1):295–300. doi: 10.1016/0003-2697(78)90304-4. [DOI] [PubMed] [Google Scholar]
  13. Kagan H. M., Hewitt N. A., Salcedo L. L., Franzblau C. Catalytic activity of aortic lysyl oxidase in an insoluble enzyme-substrate complex. Biochim Biophys Acta. 1974 Sep 13;365(1):223–234. doi: 10.1016/0005-2795(74)90267-0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Layman D. L., Narayanan A. S., Martin G. R. The production of lysyl oxidase by human fibroblasts in culture. Arch Biochem Biophys. 1972 Mar;149(1):97–101. doi: 10.1016/0003-9861(72)90302-5. [DOI] [PubMed] [Google Scholar]
  16. Melet J., Vianden G. D., Bachra B. N. Simplified assay for lysyl oxidase activity. Anal Biochem. 1977 Jan;77(1):141–146. doi: 10.1016/0003-2697(77)90298-6. [DOI] [PubMed] [Google Scholar]
  17. Morton H. J. A survey of commercially available tissue culture media. In Vitro. 1970 Sep-Oct;6(2):89–108. doi: 10.1007/BF02616112. [DOI] [PubMed] [Google Scholar]
  18. Narayanan A. S., Page R. C., Kuzan F., Cooper C. G. Elastin cross-linking in vitro. Studies on factors influencing the formation of desmosines by lysyl oxidase action on tropoelastin. Biochem J. 1978 Sep 1;173(3):857–862. doi: 10.1042/bj1730857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Oakes B. W., Danks D. M., Campbell P. E. Human copper deficiency: ultrastructural studies of the aorta and skin in a child with Menkes' syndrome. Exp Mol Pathol. 1976 Aug;25(1):82–98. doi: 10.1016/0014-4800(76)90019-8. [DOI] [PubMed] [Google Scholar]
  20. Pinnell S. R., Martin G. R. The cross-linking of collagen and elastin: enzymatic conversion of lysine in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone. Proc Natl Acad Sci U S A. 1968 Oct;61(2):708–716. doi: 10.1073/pnas.61.2.708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sandberg L. B. Elastin structure in health and disease. Int Rev Connect Tissue Res. 1976;7:159–210. doi: 10.1016/b978-0-12-363707-9.50010-1. [DOI] [PubMed] [Google Scholar]
  22. Siegel R. C. Biosynthesis of collagen crosslinks: increased activity of purified lysyl oxidase with reconstituted collagen fibrils. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4826–4830. doi: 10.1073/pnas.71.12.4826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Siegel R. C. Lysyl oxidase. Int Rev Connect Tissue Res. 1979;8:73–118. doi: 10.1016/b978-0-12-363708-6.50009-6. [DOI] [PubMed] [Google Scholar]
  24. Siegel R. C., Pinnell S. R., Martin G. R. Cross-linking of collagen and elastin. Properties of lysyl oxidase. Biochemistry. 1970 Nov 10;9(23):4486–4492. doi: 10.1021/bi00825a004. [DOI] [PubMed] [Google Scholar]
  25. Starcher B. C., Madaras J. A., Tepper A. S. Lysyl oxidase deficiency in lung and fibroblasts from mice with hereditary emphysema. Biochem Biophys Res Commun. 1977 Sep 23;78(2):706–712. doi: 10.1016/0006-291x(77)90236-4. [DOI] [PubMed] [Google Scholar]
  26. Starcher B., Madaras J. A., Fisk D., Perry E. F., Hill C. H. Abnormal cellular copper metabolism in the blotchy mouse. J Nutr. 1978 Aug;108(8):1229–1233. doi: 10.1093/jn/108.8.1229. [DOI] [PubMed] [Google Scholar]
  27. Stassen F. L. Properties of highly purified lysyl oxidase from embryonic chick cartilage. Biochim Biophys Acta. 1976 Jun 7;438(1):49–60. doi: 10.1016/0005-2744(76)90222-9. [DOI] [PubMed] [Google Scholar]
  28. Tomkins G. A., MacGregor A., Pye D., Atkinson M. Rapid detection and isolation of mycoplasmas from cell cultures. Aust J Exp Biol Med Sci. 1975 Aug;53(4):257–263. doi: 10.1038/icb.1975.28. [DOI] [PubMed] [Google Scholar]
  29. al-Rashid R. A., Spangler J. Neonatal copper deficiency. N Engl J Med. 1971 Oct 7;285(15):841–843. doi: 10.1056/NEJM197110072851506. [DOI] [PubMed] [Google Scholar]

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