Skip to main content
SpringerLink
Log in

Genetic Heterogeneity in Inherited Disorders with a Generalized Impairment of Peroxisomal Functions: Visualization by Immunofluorescence Microscopy of Peroxisome Assembly After Somatic Cell Fusion of Complementary Cell Lines

  • Conference paper
Molecular Basis of Membrane-Associated Diseases

Abstract

The cerebro-hepato-renal (Zellweger) syndrome is a rare familial disease that is characterized by a variety of biochemical and clinical aberrations [1–6]. The most striking biochemical abnormality in this disorder is the absence of morphologically distinguishable peroxisomes [7], and the deficiency of several peroxisomal enzymes [2–6] and enzyme proteins [8], In recent years other inherited diseases in man have been recognized in which there is a generalized impairment of peroxisomal functions [2–6,9,10]. These diseases include the infantile form of Refsum disease (IRD), the neonatal form of adrenoleukodystrophy (NALD) and hyperpipecolic acidaemia [2–6,9,10]. The existence of such diseases, which usually result in early death of the patients, stresses the importance of peroxisomes in cellular metabolism [9,10].

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kelley RI (1983) Review: the cerebro-hepato-renal syndrome of Zellweger, morphologic and metabolic aspects. Am J Med Genet 16:503–517

    Article  PubMed  CAS  Google Scholar 

  2. Goldfischer S, Reddy JK (1984) Peroxisomes (microbodies) in cell pathology. Int Rev Exp Pathol 26:45–84

    PubMed  CAS  Google Scholar 

  3. Moser HW (1987) New approaches in peroxisomal disorders. Dev Neurosci 9:1–18

    Article  PubMed  CAS  Google Scholar 

  4. Zellweger H (1987) The cerebro-hepato-renal (Zellweger) syndrome and other peroxisomal disorders. Dev Med Child Neurol 29:821–829

    Article  PubMed  CAS  Google Scholar 

  5. Schutgens RBH, Heymans HSA, Wanders RJA, Van Den Bosch H, Tager JM (1986) Review. Peroxisomal disorders: a newly recognized group of genetic diseases. Eur J Pediatr 144:430–440

    Article  PubMed  CAS  Google Scholar 

  6. Schutgens RBH, Wanders RJA, Schräm AW, Van Den Bosch H, Heymans HSA, Schrakamp G, Tager JM (1987) Peroxisomal disorders: biochemical characteristics and genetic relationship between the different diseases. In: Vogel F, Sperling K (eds) Human genetics. Springer, Berlin Heidelberg New York Tokyo, pp 360–368

    Google Scholar 

  7. Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis MP, Wisnewski HK, Ritch RH, Norton WT, Rapin I, Gartner LM (1973) Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science 182:62–64

    Article  PubMed  CAS  Google Scholar 

  8. Tager JM, Ten Harmsen Van Der Beek WA, Wanders RJA, Hashimoto T, Heymans HSA, Van Den Bosch H, Schutgens RBH, Schräm AW (1985) Peroxisomal β-oxidation enzyme proteins in the Zellweger syndrome. Biochem Biophys Res Commun 126:1269–1275

    Article  PubMed  CAS  Google Scholar 

  9. Goldfischer S, Collins J, Rapin I, Coltoff-Schiller B, Chang C-H, Nigro M, Black VH, Javitt NB, Moser HW, Lazarow PB (1985) Peroxisomal defects in neonatal-onset and X-linked adrenoleu-kodystrophies. Science 227:67–70

    Article  PubMed  CAS  Google Scholar 

  10. Scotto JM, Hadchouel M, Odievre M, Landat MH, Saudubray JM, Dulac O, Beucler I, Bean P (1982) Infantile phytanic acid storage disease, a possible variant of Refsum’s disease: three cases including ultrastructural studies of the liver. J Inherit Metab Dis 5:83–90

    Article  PubMed  CAS  Google Scholar 

  11. Lazarow PB, De Duve C (1976) A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug. Proc Natl Acad Sci USA 73:2043–2046

    Article  PubMed  CAS  Google Scholar 

  12. Bremer J (1977) Carnitine and its role in fatty acid metabolism. Trends Biochem Sci 2:207–209

    CAS  Google Scholar 

  13. Singh I, Moser AE, Goldfischer S, Moser HW (1984) Lignoceric acid is oxidized in the peroxisome: implications for the Zellweger cerebro-hepato-renal syndrome and adrenoleukodystrophy. Proc Natl Acad Sci USA 81:4203–4207

    Article  PubMed  CAS  Google Scholar 

  14. Diczfalusy U, Alexson SEH, Pedersen JI (1987) Chain-shortning of prostaglandin F2α by rat liver peroxisomes. Biochem Biophys Res Commun 144:1206–1213

    Article  PubMed  CAS  Google Scholar 

  15. Hajra AK, Bishop JE (1982) Glycerolipid biosynthesis in peroxisomes via the acyl dihydoxy-acetonephosphate pathway. Ann NY Acad Sci 386:170–182

    Article  PubMed  CAS  Google Scholar 

  16. Pedersen JI, Gustafsson J (1980) Conversion of 3α, 7α, Hα-trihydroxy-5β-cholestanoic acid into cholic acid by rat liver peroxisomes. FEBS Lett 121:345–348

    Article  PubMed  CAS  Google Scholar 

  17. Hagey LR, Krisans SK (1982) Degradation of cholesterol to propionic acid by rat liver peroxisomes. Biochem Biophys Res Commun 107:834–841

    Article  PubMed  CAS  Google Scholar 

  18. Wanders RJA, Romeyn GJ, van Roermund CWT, Schutgens RBH, Van Den Bosch H, Tager JM (1988) Identification of L-pipecolic oxidase in human liver and its deficiency in the Zellweger syndrome. Biochem Biophys Res Commun (in press)

    Google Scholar 

  19. Mihalik SJ, Rhead WJ (1988) Pipecolic acid is oxidized to alpha aminoadipic acid in the peroxisome of man and monkey. Trans Am Soc Neurochem 19:72 (Abstr)

    Google Scholar 

  20. Noguchi T, Takada Y (1979) Peroxisomal localization of alanine: glyoxylate aminotransferase in human liver peroxisomes. Biochem Biophys Res Commun 144:1206–1213

    Google Scholar 

  21. Danpure CJ, Jennings PR (1986) Peroxisomal alanine: glyoxylate aminotransferase deficiency in primary hyperoxaluria type 1. FEBS Lett 201:20–24

    Article  PubMed  CAS  Google Scholar 

  22. Brul S, Westerveld A, Strijland A, Wanders RJA, Schräm AW, Heymans HSA, Schutgens RBH, Van Den Bosch H, Tager JM (1988) Genetic heterogeneity in the cerebro-hepato-renal (Zellweger) syndrome and other inherited disorders with a generalized impairment of peroxisomal functions: a study using complementation analysis. J Clin Invest 81:1710–1715

    Article  PubMed  CAS  Google Scholar 

  23. Brul S, Wiemer EAC, Westerveld A, Strijland A, Wanders RJA, Schräm AW, Heymans HSA, Schutgens RBH, Van Den Bosch H, Tager JM (1988) Kinetics of the assembly of peroxisomes after fusion of complementary cell lines from patients with the cerebro-hepato-renal (Zellweger) syndrome and related disorders. Biochem Biophys Res Commun 152:1083–1089

    Article  PubMed  CAS  Google Scholar 

  24. Wanders RJA, Kos M, Roest B, Meijer AJ, Schrakamp G, Heymans HSA, Tegelaers WHH, Van Den Bosch H, Schutgens RBH, Tager JM (1984) Activity of peroxisomal enzymes and intracellular distribution of catalase in the Zellweger syndrome. Biochem Biophys Res Commun 123:1054–1061

    Article  PubMed  CAS  Google Scholar 

  25. Keller G-A, Gould S, Deluca M, Subramani S (1987) Firefly luciferase is targeted to peroxisomes in mammalian cells. Proc Natl Acad Sci USA 84:3264–3268

    Article  PubMed  CAS  Google Scholar 

  26. Gould SJ, Keller GA, Subramani S (1987) Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. J Cell Biol 105:2923–2931

    Article  PubMed  CAS  Google Scholar 

  27. Santos MJ, Imanaka T, Shio H, Small GM, Lazarow PB (1988) Peroxisomal membrane ghosts in Zellweger syndrome — aberrant organelle assembly. Science 239:1536–1538

    Article  PubMed  CAS  Google Scholar 

  28. Lazarow PB, Fujiki Y, Small GM, Watkins P, Moser H (1986) Presence of the peroxisomal 22-kDa integral membrane protein in the liver of a person lacking recognizable peroxisomes (Zellweger syndrome). Proc Natl Acad Sci USA 83:9193–9196

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Biochemistry, University of Amsterdam, P.O. Box 20151, 1000 HD, Amsterdam, The Netherlands

    S. Brul, E. A. C. Wiemer, M. Oosthuizen, R. Van Driel, A. Strijland, A. W. Schram & J. M. Tager

  2. Division of Cell Biology and Genetics, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands

    A. Westerveld

  3. Department of Pediatrics, University Hospital University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    R. B. H. Schutgens & R. J. A. Wanders

  4. Laboratory of Biochemistry, University of Utrecht, Padualaan 8, 3584 CH, Utrecht, The Netherlands

    H. Van Den Bosch

Authors
  1. S. Brul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. A. C. Wiemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Oosthuizen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Westerveld
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Van Driel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Strijland
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. B. H. Schutgens
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. Van Den Bosch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R. J. A. Wanders
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A. W. Schram
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J. M. Tager
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institut für Biochemie und Molekularbiologie, Universität Bern, Bühlstraße 28, CH-3012, Bern, Switzerland

    Angelo Azzi

  2. Institute of Physiology, Czechoslovak Academy of Sciences, Videnska 1083, CS-142 20, Praha 4, Czech Republic

    Zdenek Drahota

  3. Institute of Medical Biochemistry and Chemistry, University of Bari, Piazza G. Cesare, I-70124, Bari, Italy

    Sergio Papa

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Brul, S. et al. (1989). Genetic Heterogeneity in Inherited Disorders with a Generalized Impairment of Peroxisomal Functions: Visualization by Immunofluorescence Microscopy of Peroxisome Assembly After Somatic Cell Fusion of Complementary Cell Lines. In: Azzi, A., Drahota, Z., Papa, S. (eds) Molecular Basis of Membrane-Associated Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74415-0_35

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74415-0_35

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74417-4

  • Online ISBN: 978-3-642-74415-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation