Journal of Molecular Medicine

, Volume 88, Issue 12, pp 1233–1242 | Cite as

Intracellular ROS level is increased in fibroblasts of triple A syndrome patients

  • Barbara Kind
  • Katrin Koehler
  • Manuela Krumbholz
  • Dana Landgraf
  • Angela Huebner
Original Article


Triple A syndrome is named after the main symptoms of alacrima, achalasia, and adrenal insufficiency but also presents with a variety of neurological impairments. To investigate the causes of progressive neurodegeneration, we examined the oxidative status of fibroblast cultures derived from triple A syndrome patients in comparison to control cells. Patient cells showed a 2.1-fold increased basal level of reactive oxygen species (ROS) and a massive boost after induction of artificial oxidative stress by paraquat. We examined the expression of the ROS-detoxifying enzymes superoxide dismutase 1 and 2 (SOD1, SOD2), catalase, and glutathione reductase. The basal expression of SOD1 was significantly (1.3-fold) increased, and the expression of catalase was 0.7-fold decreased in patient cells after induction of artificial oxidative stress. We show that the mitochondrial network is 1.8-fold more extensive in patient cells compared to control fibroblasts although the maximal ATP synthesis was unchanged. Despite having the same energy potential as the controls, the patient cells showed a 1.4-fold increase in doubling time. We conclude that fibroblasts of triple A patients have a higher basal ROS level and an increased response to artificially induced oxidative stress and undergo “stress-induced premature senescence”. The increased sensitivity to oxidative stress may be a major mechanism for the neurodegeneration in triple A syndrome.


Fibroblasts Mitochondria Neurodegeneration Reactive oxygen species Triple A syndrome 



We gratefully acknowledge Sandra Jackson from the Clinic of Neurology of the Technical University Dresden, Germany and Markus Schuelke from the Department of Neuropaediatrics of the Charité University Medicine, Berlin, Germany for the methodical help and fruitful discussions. This work was supported by a grant of the Deutsche Forschungsgemeinschaft (DFG, HU895 3/3–5) to AH and a MeDDrive grant of the Medical Faculty of the Technical University Dresden, Germany to KK.

Disclosure of potential conflict of interests

The authors declare no conflict of interests related to this study.


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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Barbara Kind
    • 1
  • Katrin Koehler
    • 1
  • Manuela Krumbholz
    • 2
  • Dana Landgraf
    • 1
  • Angela Huebner
    • 1
  1. 1.Children’s HospitalTechnical University DresdenDresdenGermany
  2. 2.Department of PaediatricsUniversity of Erlangen-NurembergErlangenGermany

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