Hoepken 2007 Neurobiol Dis
Hoepken HH, Gispert S, Morales B, Wingerter O, Del Turco D, MΓΌlsch A, Nussbaum RL, MΓΌller K, DrΓΆse S, Brandt U, Deller T, Wirth B, Kudin AP, Kunz WS, Auburger G (2007) Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol Dis 25:401-11. |
Hoepken HH, Gispert S, Morales B, Wingerter O, Del Turco D, Muelsch A, Nussbaum RL, Mueller K, Droese S, Brandt U, Deller T, Wirth B, Kudin AP, Kunz WS, Auburger G (2007) Neurobiol Dis
Abstract: Oxidative stress and protein aggregation are biochemical hallmarks of Parkinsonβs disease (PD), a frequent sporadic late-onset degenerative disorder particularly of dopaminergic neurons in the substantia nigra, resulting in impaired spontaneous movement. PARK6 is a rare autosomal-recessively inherited disorder, mimicking the clinical picture of PD with earlier onset and slower progression. Genetic data demonstrated PARK6 to be caused by mutations in the protein PINK1, which is localized to mitochondria and has a serineβthreonine kinase domain. To study the effect of PINK1 mutations on oxidative stress, we used primary fibroblasts and immortalized lymphoblasts from three patients homozygous for G309D-PINK1. Oxidative stress was evident from increases in lipid peroxidation and in antioxidant defenses by mitochondrial superoxide dismutase and glutathione. Elevated levels of glutathione reductase and glutathione-S-transferase were also observed. As a putative cause of oxidation, a mild decrease in complex I activity and a trend to superoxide elevation were detectable. These data indicate that PINK1 function is critical to prevent oxidative damage and that peripheral cells may be useful for studies of progression and therapy of PARK6. β’ Keywords: Malondialdehyde, MnSOD, Glutathione, Mitochondria, Oxidative stress, PINK1, PARK6;, Fibroblasts
β’ O2k-Network Lab: NL Nijmegen Brandt U, DE Frankfurt Droese S, US CA San Francisco Nussbaum RL
Labels: MiParea: Respiration, nDNA;cell genetics, mt-Medicine, Patients
Pathology: Neurodegenerative, Parkinson's
Stress:Oxidative stress;RONS
Organism: Human
Tissue;cell: Fibroblast
Enzyme: Complex I, Marker enzyme
Coupling state: OXPHOS
HRR: Oxygraph-2k