Patient-derived fibroblasts indicate oxidative stress status and may justify antioxidant therapy in OXPHOS disorders.
Publication year
2012Source
Biochimica et Biophysica Acta. Bioenergetics, 1817, 11, (2012), pp. 1971-8ISSN
Annotation
01 november 2012
Publication type
Article / Letter to editor
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Organization
Biochemistry (UMC)
Cell Biology (UMC)
Radboudumc Extern
Human Genetics
Journal title
Biochimica et Biophysica Acta. Bioenergetics
Volume
vol. 1817
Issue
iss. 11
Page start
p. 1971
Page end
p. 8
Subject
NCMLS 4: Energy and redox metabolism; NCMLS 4: Energy and redox metabolism IGMD 8: Mitochondrial medicineAbstract
Oxidative phosphorylation disorders are often associated with increased oxidative stress and antioxidant therapy is frequently given as treatment. However, the role of oxidative stress in oxidative phosphorylation disorders or patients is far from clear and consequently the preventive or therapeutic effect of antioxidants is highly anecdotic. Therefore, we performed a systematic study of a panel of oxidative stress parameters (reactive oxygen species levels, damage and defense) in fibroblasts of twelve well-characterized oxidative phosphorylation patients with a defect in the POLG1 gene, in the mitochondrial DNA-encoded tRNA-Leu gene (m.3243A>G or m.3302A>G) and in one of the mitochondrial DNA-encoded NADH dehydrogenase complex I (CI) subunits. All except two cell lines (one POLG1 and one tRNA-Leu) showed increased reactive oxygen species levels compared with controls, but only four (two CI and two tRNA-Leu) cell lines provided evidence for increased oxidative protein damage. The absence of a correlation between reactive oxygen species levels and oxidative protein damage implies differences in damage prevention or correction. This was investigated by gene expression studies, which showed adaptive and compensating changes involving antioxidants and the unfolded protein response, especially in the POLG1 group. This study indicated that patients display individual responses and that detailed analysis of fibroblasts enables the identification of patients that potentially benefit from antioxidant therapy. Furthermore, the fibroblast model can also be used to search for and test novel, more specific antioxidants or explore ways to stimulate compensatory mechanisms.
This item appears in the following Collection(s)
- Academic publications [238426]
- Faculty of Medical Sciences [90358]
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