title: Arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder.
abstract: BACKGROUND
  Zellweger spectrum disorders (ZSDs) are multisystem genetic disorders caused by a lack of functional peroxisomes, due to mutations in one of the PEX genes, encoding proteins involved in peroxisome biogenesis. The phenotypic spectrum of ZSDs ranges from an early lethal form to much milder presentations. In cultured skin fibroblasts from mildly affected patients, peroxisome biogenesis can be partially impaired which results in a mosaic catalase immunofluorescence pattern. This peroxisomal mosaicism has been described for specific missense mutations in various PEX genes. In cell lines displaying peroxisomal mosaicism, peroxisome biogenesis can be improved when these are cultured at 30°C. This suggests that these missense mutations affect the folding and/or stability of the encoded protein. We have studied if the function of mutant PEX1, PEX6 and PEX12 can be improved by promoting protein folding using the chemical chaperone arginine.
  
  
  METHODS
  Fibroblasts from three PEX1 patients, one PEX6 and one PEX12 patient were cultured in the presence of different concentrations of arginine. To determine the effect on peroxisome biogenesis we studied the following parameters: number of peroxisome-positive cells, levels of PEX1 protein and processed thiolase, and the capacity to β-oxidize very long chain fatty acids and pristanic acid.
  
  
  RESULTS
  Peroxisome biogenesis and function in fibroblasts with mild missense mutations in PEX1, 6 and 12 can be improved by arginine.
  
  
  CONCLUSIONS
  Arginine may be an interesting compound to promote peroxisome function in patients with a mild peroxisome biogenesis disorder.
authors.affiliation: Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University Hospital of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. h.r.waterham@amc.uva.nl.
authors.forename: Kevin
authors.initials: K
authors.lastname: Berendse
authors.forename: Merel S
authors.initials: MS
authors.lastname: Ebberink
authors.forename: Lodewijk
authors.initials: L
authors.lastname: Ijlst
authors.forename: Bwee Tien
authors.initials: BT
authors.lastname: Poll-The
authors.forename: Ronald J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D029681:Arabidopsis Proteins / Q000235:genetics; D001120:Arginine / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000235:genetics; D008856:Microscopy, Fluorescence; D000074401:Peroxins; D018901:Peroxisomal Disorders / Q000378:metabolism*; D020675:Peroxisomes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D029681:Arabidopsis Proteins; D008565:Membrane Proteins; D000074401:Peroxins; C507147:peroxin 12 protein, Arabidopsis; D001120:Arginine; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C111808:PEX1 protein, human; C490759:PEX6 protein, human
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