| Intracellular ROS level is increased in fibroblasts of triple A syndrome patients. | |
| | |
MedLine Citation:
|
PMID: 20706703 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
Barbara Kind; Katrin Koehler; Manuela Krumbholz; Dana Landgraf; Angela Huebner |
Related Documents
:
|
927453 - Abnormality of a thiamine-requiring enzyme in patients with wernicke-korsakoff syndrome. 9557893 - Retinal changes and tumorigenesis in ramon syndrome: follow-up of a brazilian family. 20652113 - Wells syndrome with multiorgan involvement mimicking hypereosinophilic syndrome. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-13 |
Journal Detail:
|
Title: Journal of molecular medicine (Berlin, Germany) Volume: 88 ISSN: 1432-1440 ISO Abbreviation: J. Mol. Med. Publication Date: 2010 Dec |
Date Detail:
|
Created Date: 2010-11-16 Completed Date: 2011-04-04 Revised Date: 2011-07-08 |
Medline Journal Info:
|
Nlm Unique ID: 9504370 Medline TA: J Mol Med (Berl) Country: Germany |
Other Details:
|
Languages: eng Pagination: 1233-42 Citation Subset: IM |
Affiliation:
|
Children's Hospital, Technical University Dresden, Fetscherstr. 74, 01307, Dresden, Germany. barbara.kind@uniklinikum-dresden.de |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenal Insufficiency
/
enzymology,
metabolism Catalase / genetics, metabolism Cell Proliferation Child Child, Preschool Esophageal Achalasia / enzymology, metabolism Female Fibroblasts / metabolism* Gene Expression Regulation, Enzymologic Glutathione Peroxidase / genetics, metabolism Humans Infant Intracellular Space / metabolism* Male Membrane Potential, Mitochondrial Models, Biological Phenanthridines / metabolism Reactive Oxygen Species / metabolism* Reverse Transcriptase Polymerase Chain Reaction Rhodamines / metabolism Superoxide Dismutase / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/5-(6'-triphenylphosphoniumhexyl)-5,6-dihydro-6-phenyl-3,8-phenanthridinediammine; 0/Phenanthridines; 0/Reactive Oxygen Species; 0/Rhodamines; 109244-58-8/dihydrorhodamine 123; EC 1.11.1.6/Catalase; EC 1.11.1.9/Glutathione Peroxidase; EC 1.15.1.-/superoxide dismutase 1; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: [Infections and chronic spontaneous urticaria. A review].
Next Document: Sexual dimorphism in immune function changes during the annual cycle in house sparrows.