Molecular Diagnosis & Therapy

, Volume 20, Issue 2, pp 125–133 | Cite as

Effect of Cysteamine on Mutant ASL Proteins with Cysteine for Arginine Substitutions

  • Corinne Inauen
  • Véronique Rüfenacht
  • Amit V. Pandey
  • Liyan Hu
  • Henk Blom
  • Jean-Marc Nuoffer
  • Johannes HäberleEmail author
Short Communication



Cysteamine is used to treat cystinosis via the modification of cysteine residues substituting arginine in mutant proteins.


We investigated the effect of cysteamine on mutant argininosuccinate lyase (ASL), the second most common defect in the urea cycle.


In an established mammalian expression system, 293T cell lysates were produced after transfection with all known cysteine for arginine mutations in the ASL gene (p.Arg94Cys, p.Arg95Cys, p.Arg168Cys, p.Arg379Cys, and p.Arg385Cys), allowing testing of the effect of cysteamine over 48 h in the culture medium as well as for 1 h immediately prior to the enzyme assay.


Cysteamine at low concentrations showed no effect on 293T cell viability, ASL protein expression, or ASL activity when applied during cell culture. However, incubation of transfected cells with 0.05 mM cysteamine immediately before the enzyme assay resulted in increased ASL activity of p.Arg94Cys, p.Arg379Cys, and p.Arg385Cys by 64, 20, and 197 %, respectively, and this result was significant (p < 0.01). Cell lysates carrying p.Arg385Cys and treated with cysteamine recover enzyme activity that is similar to the untreated designed mutation p.Arg385Lys, providing circumstantial evidence for the assumed cysteamine-induced change of a cysteine to a lysine analogue.


Since 12 % of all known genotypes in ASL deficiency are affected by a cysteine for arginine mutation, we conclude that the potential of cysteamine or of related substances as remedy for this disease should be investigated further.


293T Cell Cysteamine Cystinosis Urea Cycle Disorder Transfected 293T Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Compliance with Ethical Standards

Conflict of interest

The authors CI, VR, AVP, LH, HB, JMN, and JH declare that they have no conflicts of interest.


This work was supported by the Swiss National Science Foundation (Grants 310030_153196/1 to JH and 310031_134926 to AVP) and a grant from Schweizerische Mobiliar Genossenschaft Jubiläumsstiftung to AVP.

Supplementary material

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Supplementary material 1 (TIFF 50 kb)
40291_2015_182_MOESM2_ESM.docx (26 kb)
Supplementary material 2 (DOCX 25 kb)


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Corinne Inauen
    • 1
  • Véronique Rüfenacht
    • 1
  • Amit V. Pandey
    • 2
  • Liyan Hu
    • 1
    • 3
  • Henk Blom
    • 4
  • Jean-Marc Nuoffer
    • 5
    • 6
  • Johannes Häberle
    • 1
    • 3
    • 7
    Email author
  1. 1.Division of Metabolism and Children’s Research Centre (CRC)University Children’s Hospital ZürichZurichSwitzerland
  2. 2.Pediatric Endocrinology, University Children’s Hospital and Department of Clinical ResearchUniversity of BernBernSwitzerland
  3. 3.Affiliated with the Neuroscience Center Zürich (ZNZ)ZurichSwitzerland
  4. 4.Department of General Pediatrics, Adolescent Medicine and NeonatologyUniversity Medical Centre FreiburgFreiburgGermany
  5. 5.University Institute of Clinical ChemistryUniversity of BernBernSwitzerland
  6. 6.University Children’s HospitalUniversity of BernBernSwitzerland
  7. 7.Affiliated with the Zürich Center for Integrative Human Physiology (ZIHP)ZurichSwitzerland

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