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Oxidative stress in skin fibroblasts cultures from patients with Parkinson's disease
© del Hoyo et al; licensee BioMed Central Ltd. 2010
Received: 30 March 2010
Accepted: 19 October 2010
Published: 19 October 2010
In the substantia nigra of Parkinson's disease (PD) patients, increased lipid peroxidation, decreased activities of the mitochondrial complex I of the respiratory chain, catalase and glutathione-peroxidase, and decreased levels of reduced glutathione have been reported. These observations suggest that oxidative stress and mitochondrial dysfunction play a role in the neurodegeneration in PD. We assessed enzymatic activities of respiratory chain and other enzymes involved in oxidative processes in skin fibroblasts cultures of patients with PD.
We studied respiratory chain enzyme activities, activities of total, Cu/Zn- and Mn-superoxide-dismutase, gluthatione-peroxidase and catalase, and coenzyme Q10 levels in skin fibroblasts cultures from 20 Parkinson's disease (PD) patients and 19 age- and sex- matched healthy controls.
When compared with controls, PD patients showed significantly lower specific activities for complex V (both corrected by citrate synthase activity and protein concentrations). Oxidized, reduced and total coenzyme Q10 levels (both corrected by citrate synthase and protein concentrations), and activities of total, Cu/Zn- and Mn-superoxide-dismutase, gluthatione-peroxidase and catalase, did not differ significantly between PD-patients and control groups. Values for enzyme activities in the PD group did not correlate with age at onset, duration, scores of the Unified Parkinson's Disease Rating scales and Hoehn-Yahr staging.
The main result of this study was the decreased activity of complex V in PD patients. This complex synthesizes ATP from ADP using an electrochemical gradient generated by complexes I-IV. These results suggest decreased energetic metabolism in fibroblasts of patients with PD.
The pathogenesis of the neuronal degeneration of neurons in the pars compacta of the substantia nigra in patients with Parkinson's disease (PD) is unknown. The discovery that the 1-methyl-4-phenyl-pyridinium ion (MPP+), the metabolite of the parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) did inhibit complex I [1–3] led some investigators to examine the mitochondrial function in idiopathic PD.
The mitochondrial respiratory chain consists of five enzymatic complexes located within the inner mitochondrial membrane. Four enzymes (complexes I-IV) transport electrons from NADH or succinate to oxygen, and these complexes pump protons out of the mitochondria to form an electrochemical gradient. Complex V (ATP synthase) uses that electrochemical gradient to synthesize ATP from ADP.
Many studies have shown decreased complex I activity in the substantia nigra of PD patients (reviewed in reference ). More recently, Parker et al.  found decreased complex I activity in frontal cortex as well. However, the results of studies measuring mitochondrial complexes in peripheral tissues have been controversial (reviewed in reference ). The activity of mitochondrial complexes has been measured in the following tisues:
Skeletal muscle (most studies performed with isolated mitochondria). There have been reported normal activities of mitochondrial respiratory chain complexes I-IV [6–10], or decreased activities of complexes I [11–16], II [11–14] or IV [15–17].
Platelets (most studies performed with isolated mitochondria). There have been reported normal activities [6, 18–20], or decreased activities of complex I [21–26], complex II+III  or complex IV .
Lymphocytes. Studies with homogenates showed decreased activities of complex II  or complexes I and IV , while studies with isolated mitochondria showed normal activities , or decreased activity of complexes I and I+III , and complex IV .
Leukocytes: Muftuoglu et al.  reported decreased complexes I and IV activities in leukocytes from patients with idiopathic PD, and decreased complex I activity, with normality of complex IV, in patients with parkin mutations.
Spermatozoa. Our group showed similar mitochondrial respiratory chain enzymes activities corrected by citrate synthase (CS), in the spermatozoa from untreated PD patients .
A study on mitochondrial function of skin fibroblasts from PD showed a deficiency in complexes I and IV [32, 33] that was partially restored with coenzyme Q10 treatment . Piccoli et al.  examined mitochondrial respiratory function of a patient affected by early-onset parkinsonism carrying the homozygous W437X nonsense mutation in the PINK1 gene, and found decreased complex IV activity and some depression of the ATPase activity. In a recent study, Ferrer et al.  have shown decreased levels of ATP synthase in the substantia nigra and increased levels in the frontal cortex of patients with PD.
The study of mitochondrial function in PD might be important because, together with the classical description of oxidative stress and mitochondrial dysfunction in the brains of patients with this disease, the identification of specific gene mutations that cause PD has reinforced their relevance. Proteins associated with familial PD, such as PTEN-induced putative kinase 1 (PINK1), DJ-1, alpha-synuclein, leucine-rich repeat kinase 2 (LRRK2) and, possibly, parkin, are either mitochondrial proteins or are associated with mitochondria, and have a role on oxidative stress .
Some authors described decreased activities of the antioxidant enzymes glutathione-peroxidase (GPx) [37, 38], total superoxide-dismutase (SOD) , Mn-SOD , Cu,Zn-SOD , and catalase , in the substantia nigra of PD patients; while Mn-SOD activity in the cortex of PD patients has been found increased [35, 42]. GPx activity has been studied in serum or plasma, erythrocytes, and neutrophils; total SOD, Cu,Zn-SOD and/or Mn-SOD levels or activities in serum or plasma, cerebrospinal fluid, erythrocytes, neutrophils, platelets, and lymphocytes; and catalase activity in erythrocytes from PD patients. The results of these studies (reviewed in reference ) are controversial. Piccoli et al. , in their patient with the homozygous W437X nonsense mutation in the PINK1 gene described normal levels of total glutathione, reduced glutathione and glutathione peroxidase activity, normal Cu/Zn-SOD activity and a small decrease of the mitochondrial Mn-SOD in fibroblasts. To our knowledge activity of catalase has not been studied previously in fibroblasts.
Coenzyme Q10 (CoQ10) is the electron acceptor for mitochondrial complexes I and II and a powerful antioxidant . Shults et al.  reported a correlation between mitochondrial CoQ10 levels and activities of complexes I and II/III. Gotz et al.  reported a decreased [reduced CoQ10/oxidized CoQ10] ratio (redox ratio) in untreated PD patients, that was further decreased by levodopa treatment and partially restored with selegiline. Serum or plasma CoQ10 levels have been described decreased, normal or increased in some studies (reviewed in reference ). To our knowledge, CoQ10 levels in fibroblasts of PD patients have not been measured previosly.
The aim of this study was to assess the enzymatic activities of respiratory chain enzymes and other enzymes involved in oxidative processes, such as GPx, SOD, catalase and coenzyme Q10 in skin fibroblast cultures from patients with PD. The study was carried out in skin fibroblasts because the specimens were easily accessible and should be free of influence from medication, environmental hazards and other possible factors contributing to oxidative stress.
Patients and controls
Twenty patients diagnosed with PD and 19 healthy age- and sex-matched controls were enrolled in this study, after informed consent. The study was approved by the Ethics Committees of the University Hospitals "Doce de Octubre" and "Príncipe de Asturias", and was conducted according to the declaration of Helsinki. Two patients received no treatment, while the other 18 were treated with antiparkinsonian drugs alone or in combination including levodopa (16 cases), dopamine agonists (14 cases), selegiline or rasagiline (8 cases), anticholinergics (3 cases), and amantadine (1 case).
Clinical data of Parkinson's disease (PD) and control patients groups.
PARKINSON'S DISEASE (n = 20)
CONTROLS (n = 19)
MEAN (SD) AGE (years)
MEAN (SD) AGE AT ONSET OF PD (years)
MEAN (SD) DURATION OF PD (years)
The following exclusion criteria were applied both to patients and controls: A) Ethanol intake higher than 80 g/day in the last 6 months. B) Previous history of chronic hepatopathy or diseases causing malabsorption. C) Previous history of severe systemic disease. D) Atypical dietary habits (diets constituted exclusively by one type of foodstuff, such as vegetables, fruits, meat, or others, special diets because of religious reasons, etc) F) Intake of drugs which modify lipid absorption. G) Therapy with vitamin supplements in the last 6 months.
Skin fibroblast cultures
Human skin fibroblasts were obtained from the dorsal region of the upper arm of each PD patient or control. Fibroblasts from the biopsy specimens were cultured in Dulbecco's modified Eagle's medium containing penicillin (100 UI/mL), streptomycin (100 mg/dl), L-glutamine (4 mM) and supplemented with heat-inactivated fetal calf serum at 37°C in a humidified atmosphere of 95% air and 5% CO2. Cells were grown to confluence, harvested by trypsinization at 37°C, washed with culture medium and resuspended with phosphate buffer 20 mM, and then sonicated to obtain the cell homogenate. Care was taken not to use cultures with a passage number greater than 12.
Respiratory chain enzymes assay
Mean (SD) respiratory chain enzymes activities (expressed as nmol/min/mg protein) in skin fibroblast cultures of patients with Parkinson's disease (PD) and controls (CS = citrate synthase).
PARKINSON'S DISEASE (n = 20)
CONTROLS (n = 19)
COMPLEX I + III/CS
COMPLEX II + III/CS
COMPLEX I + III/protein
COMPLEX II + III/protein
Glutathione-peroxidase, catalase and superoxide-dismutase isoenzymes determination
Glutathione peroxidase specific activity was determined according to the method described by Flohé and Günzler  based on NADPH oxidation followed at 340 nm at 37°C.
Catalase activity was determined according to the method described by Aeby  based on H2O2 decomposition followed at 240 nm at room temperature. Catalase specific activity was determined by calculating the rate constant of a first order reaction.
Total and Mn-SOD activities were determined according to the method described by Spitz and Oberley  based on nitroblue tetrazolium reduction by superoxide radicals followed at 560 nm at room temperature. The Mn-SOD was distinguished from cyanide-sensitive Cu/Zn-SOD by the addition of 5 mM NaCN. Cu/Zn-SOD activity was calculated by substracting the cyanide-resistant SOD activity form the total SOD activity. One unit of SOD activity is defined as the amount of enzyme that inhibits the reaction rate by 50%.
All enzymatic activities were expressed as values normalized to total cellular protein. The measurements were performed three times for every sample.
Oxidized, reduced and total coenzyme Q10 levels were determined by high performance liquid chromatography with electrochemical detection. The method used was that of Langedijk et al.  with some modifications. The stationary phase was a reverse phase column (HR-80 RP-C18, 80 × 4,6 mm. ESA Inc). The mobile phase was prepared by dissolving 7 g of NaClO4.H2O in 1000 ml of methanol/propanol/HClO4 70%, 700.8:200:0.2 (vol/vol), and the flow rate was set at 0.8 ml/min. The programmed conditions for the electrochemical detector and the post-column valve were the same. The system was entirely controlled by a computer (Kromasystem 2000, Kontron Instruments). Injections were made in a 50 μl injection valve (Model 7161, Rheodyne, Cotaty, USA) with a 100 μl syringe from Hamilton (Bonaduz, Switzerland). The calibration method used ubiquinone as external standard. The within-run coefficients of variation for CoQ10 and CoQH2 were, respectively, 5 and 3.2%, and the day to day precisions were 9.2 and 6.3%. CoQ10 recovery ranged between 88 and 93%. The measurements of CoQ10 were expressed in nmol/g of protein. The measures were performed three times for every sample.
Results were expressed as mean ± SD. Statistical analysis was done by the SPSS statistical package (15.0 version). For continuous variables the Kolmogorov-Smirnoff test was used to analyze normality in the distribution. Then, the Students's two-sample t-test was used for variables that followed a normal distribution and the Mann-Whitney test was used for the rest of variables. The results of each table were corrected for multiple comparisons by the use of Bonferroni's correction. Correlation analyses were performed by using Pearson's correlation coefficient.
Mean (SD) superoxide-dismutase (SOD), glutathione-peroxidase (GPx), and catalase activities (expressed as units/mg protein); and concentrations of coenzyme Q10 (expressed in nmol/g protein) in skin fibroblast cultures of patients with Parkinson's disease (PD) and controls (CS = citrate synthase).
PARKINSON'S DISEASE(n = 20)
CONTROLS (n = 19)
OXIDIZED Q10/Reduced Q10
The results of the present study showed that in PD patients there was a decreased activity of mitochondrial respiratory chain complex V, corrected by CS activity, in skin fibroblast cultures. The results on complexes I and IV in this study did not differ significantly between PD patients and control groups, and none of our patients showed decreased activities of these complexes. These results contrast with those reported by other group [32, 33], who found a deficiency in complexes I and IV activities, specially in a subgroup of PD patients compared with controls, using skin fibroblast cultures as well. This deficiency was partially restored with coenzyme Q10 treatment .
The discrepancies between the results on complex I and IV of the present study and those of Winkler-Stuck et al. [32, 33] could be related with several methodological reasons. These authors found enhanced flux control coefficient of complex I and IV. This kind of variation was measured using inhibitor titrations and calculating the flux control coefficients from titration curves. The method used by Winkler-Stuck et al. [32, 33] is different from that used in our study, because we only have measured, in the case of mitochondrial respiratory chain complex activities, the activity of every complex, and not the flux control coefficient. In addition, the control groups were different, because while Winkler-Stuck et al. [32, 33] included patients who performed muscle biopsy because they had discrete myopathic EMG abnormalities but withoutt biopsy evidence of myopathy, while our control patients had no clinical symptoms or signs suggesting myopathy. Winkler-Stuck et al. [32, 33] did not measure complex V activity.
Our results suggest that decreased complex I activity seen in the substantia nigra of PD patients is not a generalised phenomenon. It is of note that complex V has not been usually studied neither in brain nor in peripheral tissues from PD patients. Indeed, complex V was not measured in previous studies by our group using isolated mitochondria from lymphocytes  or spermatozoa  or in other report using skin fibroblasts [32, 33]. Cardellach et al.  found decreased complex V activity in muscle of 2 out of their 8 parkinsonian patients and, more recently, Ferrer et al.  found decreased levels of ATP-synthase (complex V) in the substantia nigra and increased levels of this enzymatic complex in the frontal cortex of patients with PD.
The activities of Cu/Zn- and Mn-SOD, GPx, and catalase, and the oxidized, reduced, and total CoQ10 levels in skin fibroblasts of PD patients were similar to those of controls. To our knowledge, these values have not been previously measured in this tissue form, with the exception of the single patient with a mutation in the PINK1 gene reported by Piccoli et al. . These results do not rule out the possibility that there may be regional deficiencies of the activities of these enzymes and of CoQ10 concentrations in some areas of the brain. Moreover, none of the enzymatic activities measured was correlated with the analyzed clinical features of PD.
The main result of the present study in skin fibroblasts cultures suggests a possible contribution of the deficiency of complex V activity, but not of other enzymes related with oxidative stress, to the pathogenesis of PD. This result is in agreement with that reported by Ferrer et al  in the PD substantia nigra, which was interpreted by the authors as related with neuronal loss. Complex V is involved in the synthesis of ATP from ADP, and is very important in the energetic metabolism of the cells. The result of the present study suggests decreased energetic metabolism in fibroblasts of patients with PD.
This work was supported in part by the grant of the Fondo de Investigaciones Sanitarias 99/0518 and Neuro-Magister S.L.U.
- Nicklas WJ, Vyas I, Heikkila RE: Inhibition of NADH-linked oxidation in brain mitochondria by 1-methyl-4-phenylpyridine, a metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Life Sciences. 1985, 36: 2503-2508. 10.1016/0024-3205(85)90146-8.View ArticlePubMedGoogle Scholar
- Vyas I, Heikkila RE, Nicklas WJ: Studies on the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: inhibition of NAD-linked substrate oxidation by its metabolite, 1-methyl-4-phenyl-pyridinium. Journal of Neurochemistry. 1986, 46: 1501-1507. 10.1111/j.1471-4159.1986.tb01768.x.View ArticlePubMedGoogle Scholar
- Mizuno Y, Saitoh T, Sone N: Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity by 1-methyl-4-phenylpyridinium ion. Biochemical and Biophysica. Research Communications. 1987, 143: 294-299. 10.1016/0006-291X(87)90664-4.View ArticleGoogle Scholar
- Alonso-Navarro H, Jiménez-Jiménez FJ, Pilo de la Fuente B, Plaza-Nieto JF: Mecanismos patogénicos de la enfermedad de Parkinson. Tratado de los Trastornos del Movimiento. 2nd edition (ISBN 978-84-85424-76-4). Edited by: Jiménez-Jiménez FJ, Luquin MR, Molina JA, Linazasoro G. 2008, Barcelona: Viguera Editores S.L, 425-485.Google Scholar
- Parker WD, Parks JK, Swerdlow RH: Complex I deficiency in Parkinson's disease frontal cortex. Brain Research. 2008, 1189: 215-218. 10.1016/j.brainres.2007.10.061.View ArticlePubMedGoogle Scholar
- Mann V, Cooper JM, Krige D, Daniel SE, Schapira AH, Marsden CD: Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease. Brain. 1992, 115: 333-342. 10.1093/brain/115.2.333.View ArticlePubMedGoogle Scholar
- Anderson JJ, Bravi D, Ferrari R, Davis TL, Baronti F, Chase TN, Dagani F: No evidence for altered mitochondrial function in Parkinson's disease. Journal of Neurology, Neurosurgery, and Psychiatry. 1993, 56: 477-480. 10.1136/jnnp.56.5.477.View ArticlePubMedPubMed CentralGoogle Scholar
- Di Donato S, Zeviani M, Giovannini P, Savarese N, Rimoldi M, Mariotti C, Girotti F, Caraceni T: Respiratory chain and mitochondrial DNA in muscle and brain in Parkinson's disease patients. Neurology. 1993, 43: 2262-2268.View ArticleGoogle Scholar
- Di Monte DA, Sandy MS, Jewell SA, Langston JW: Oxidative phosphorylation by intact muscle mitochondrial function in Parkinson's disease. Neurodegeneration. 1993, 2: 275-281.Google Scholar
- Reichmann H, Janetzky B, Bischop F, Seibel P, Schöls L, Kuhn W, Przuntek H: Unaltered respiratory chain enzyme activity and mitochondrial DNA in skeletal muscle of patients with idiopathic Parkinson's syndrome. European Neurology. 1994, 34: 263-267. 10.1159/000117053.View ArticlePubMedGoogle Scholar
- Bindoff LA, Birch-Machin M, Cartlidge NE, Parker WD, Turnbull DM: Mitochondrial function in Parkinson's disease. The Lancet. 1989, 2: 49-10.1016/S0140-6736(89)90291-2.View ArticleGoogle Scholar
- Bindoff LA, Birch-Machin M, Cartlidge NE, Parker WD, Turnbull DM: Respiratory chain abnormalities in skeletal muscle from patients with Parkinson's disease. Journal of the Neurological Sciences. 1991, 104: 203-208. 10.1016/0022-510X(91)90311-T.View ArticlePubMedGoogle Scholar
- Nakagawa-Hattori Y, Yoshino H, Kondo T, Mizuno Y, Horai S: Is Parkinson's disease a mitochondrial disease?. Journal of the Neurological Sciences. 1992, 107: 29-33. 10.1016/0022-510X(92)90205-Y.View ArticlePubMedGoogle Scholar
- Shoffner JM, Watts RL, Juncos JL, Torroni A, Wallace DC: Mitochondrial oxidative phosphorylation defects in Parkinson's disease. Annals of Neurology. 1992, 32: 226-227. 10.1002/ana.410320221.View ArticleGoogle Scholar
- Cardellach F, Martí MJ, Fernández-Sola J, Marín C, Hoek B, Tolosa E, Urbano-Márquez A: Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease. Neurology. 1993, 43: 2258-2262.View ArticlePubMedGoogle Scholar
- Blin O, Desnuelle C, Rascol O, Borg M, Peyro-Saint Paul H, Azulay JP, Bille F, Figarella D, Coulom F, Pellissier JF, et al: Mitochondrial respiratory failure in skeletal muscle from patients with Parkinson's disease and multiple system atrophy. Journal of the Neurological Sciences. 1994, 125: 95-101. 10.1016/0022-510X(94)90248-8.View ArticlePubMedGoogle Scholar
- Winkler-Stuck K, Kirches E, Mawrin C, Dietzmann K, Lins H, Wallesch CW, Kunz WS, Wiedemann FR: Re-evaluation of the dysfunction of mitochondrial respiratory chain in skeletal muscle of patients with Parkinson's disease. Journal of Neural Transmission. 2005, 112: 499-518. 10.1007/s00702-004-0195-y.View ArticlePubMedGoogle Scholar
- Bravi D, Anderson JJ, Dagani F, Davis TL, Ferrari R, Gillespie M, Chase TN: Effect of aging and dopaminomimetic therapy on mitochondrial respiratory function in Parkinson's disease. Movement Disorders. 1992, 7: 228-231. 10.1002/mds.870070307.View ArticlePubMedGoogle Scholar
- Blake CI, Spitz E, Leehey M, Hoffer BJ, Boyson SJ: Platelet mitochondrial respiratory chain function in Parkinson's disease. Movement Disorders. 1997, 12: 3-8. 10.1002/mds.870120103.View ArticlePubMedGoogle Scholar
- Hanagasi HA, Ayribas D, Baysal K, Emre M: Mitochondrial complex I, II/III, and IV activities in familial and sporadic Parkinson's disease. International Journal of Neurosciences. 2005, 115: 479-493. 10.1080/00207450590523017.View ArticleGoogle Scholar
- Parker WD, Boyson SJ, Parks JK: Abnormalities of the electron transport chain in idiopathic Parkinson's disease. Annals of Neurology. 1989, 26: 719-723. 10.1002/ana.410260606.View ArticlePubMedGoogle Scholar
- Krige D, Carrol MT, Cooper JM, Marsden CD, Schapira AH: Platelet mitochondrial function in Parkinson's disease. The Royal Kings and Queens Parkinson Disease Research Group. Annals of Neurology. 1992, 32: 782-788. 10.1002/ana.410320612.View ArticlePubMedGoogle Scholar
- Yoshino H, Nakagawa-Hattori Y, Kondo T, Mizuno Y: Mitochondrial complex I and II activities of lymphocytes and platelets in Parkinson's disease. Journal of Neural Transmission (Parkinson's Disease Section). 1992, 4: 27-34. 10.1007/BF02257619.View ArticleGoogle Scholar
- Benecke R, Strumper P, Weiss H: Electron transfer complexes I and IV of platelets are abnormal in Parkinson's disease but normal in Parkinson-plus syndromes. Brain. 1992, 116: 1451-1463. 10.1093/brain/116.6.1451.View ArticleGoogle Scholar
- Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW: Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson's disease. Annals of Neurology. 1995, 37: 714-722. 10.1002/ana.410370604.View ArticlePubMedGoogle Scholar
- Varghese M, Pandey M, Samanta A, Gangopadhyay PK, Mohanakumar KP: Reduced NADH coenzyme Q dehydrogenase activity in platelets of Parkinson's disease, but not Parkinson plus patients, from an Indian population. Journal of the Neurological Sciences. 2009, 279: 39-42. 10.1016/j.jns.2008.12.021.View ArticlePubMedGoogle Scholar
- Barroso N, Campos Y, Huertas R, Esteban J, Molina JA, Alonso A, Gutiérrez-Rivas E, Arenas J: Respiratory chain enzyme activities in lymphocytes from untreated patients with Parkinson disease. Clinical Chemistry. 1993, 39: 667-669.PubMedGoogle Scholar
- Martín MA, Molina JA, Jiménez-Jiménez FJ, Benito-León J, Ortí-Pareja M, Campos Y, Arenas J, Grupo Centro de Trastornos del Movimiento: Respiratory chain enzyme activities in isolated mitochondria of lymphocytes from untreated Parkinson's disease patients. Neurology. 1996, 46: 1343-1346.View ArticlePubMedGoogle Scholar
- Shinde S, Pasupathy K: Respiratory-chain enzyme activities in isolated mitochondria of lymphocytes from patients with Parkinson's disease: preliminary study. Neurology India. 2006, 54: 390-393. 10.4103/0028-3886.28112.View ArticlePubMedGoogle Scholar
- Muftuoglu M, Elibol B, Dalmizrak O, Ercan A, Kulaksiz G, Ogus H, Dalkara T, Ozer N: Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations. Movement Disorders. 2004, 19: 544-548. 10.1002/mds.10695.View ArticlePubMedGoogle Scholar
- Molina JA, Ruiz-Pesini E, Jiménez-Jiménez FJ, López-Pérez MJ, Alvarez E, Berbel A, Ortí-Pareja M, Zurdo M, Tallón-Barranco A, de Bustos F, Arenas J: Respiratory chain enzyme activity in spermatozoa from untreated Parkinson's disease patients. Journal of Neural Transmission. 1999, 106: 919-924. 10.1007/s007020050211.View ArticlePubMedGoogle Scholar
- Wiedemann FR, Winkler K, Lins H, Wallesch CW, Kunz WS: Detection of respiratory chain defects in cultivated skin fibroblasts and skeletal muscle of patients with Parkinson's disease. Annals of the New York Academy of Sciences. 1999, 893: 426-429. 10.1111/j.1749-6632.1999.tb07870.x.View ArticlePubMedGoogle Scholar
- Winkler-Stuck K, Wiedemann FR, Wallesch CW, Kunz WS: Effect of coenzyme Q10 on the mitochondrial function of skin fibroblasts from Parkinson patients. Journal of the Neurological Sciences. 2004, 220: 41-48. 10.1016/j.jns.2004.02.003.View ArticlePubMedGoogle Scholar
- Piccoli C, Sardanelli A, Scrima R, Ripoli M, Quarato G, D'Aprile A, Bellomo F, Scacco S, De Michele G, Filla A, Iuso A, Boffoli D, Capitanio N, Papa S: Mitochondrial respiratory dysfunction in familiar parkinsonism associated with PINK1 mutation. Neurochemical Research. 2008, 33: 2565-2574. 10.1007/s11064-008-9729-2.View ArticlePubMedGoogle Scholar
- Ferrer I, Pérez E, Dalfó E, Barrachina M: Abnormal levels of prohibitin and ATP synthase in the substantia nigra and frontal cortex in Parkinson's disease. Neuroscience Letters. 2007, 415: 205-209. 10.1016/j.neulet.2007.01.026.View ArticlePubMedGoogle Scholar
- Schapira AHV: Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurology. 2008, 7: 97-109. 10.1016/S1474-4422(07)70327-7.View ArticlePubMedGoogle Scholar
- Ambani LM, Van Woert MH, Murphy S: Brain peroxidase and catalase in Parkinson disease. Archives of Neurology. 1975, 32: 114-118.View ArticlePubMedGoogle Scholar
- Kish SJ, Morito C, Hornykiewicz O: Glutathione peroxidase activity in Parkinson's disease. Neuroscience Letters. 1985, 58: 343-346. 10.1016/0304-3940(85)90078-3.View ArticlePubMedGoogle Scholar
- Marttila RJ, Lorentz H, Rinne UK: Oxygen toxicity protecting enzymes in Parkinson's disease: increase of superoxide dismutase-like activity in the substantia nigra and basal nucleus. Journal of the Neurological Sciences. 1988, 86: 321-331. 10.1016/0022-510X(88)90108-6.View ArticlePubMedGoogle Scholar
- Saggu H, Cooksey J, Dexter D, Wells FR, Lees A, Jenner P, Marsden CD: A selective increase in particulate superoxide dismutase activity in parkinsonian substantia nigra. Journal of Neurochemistry. 1989, 53: 692-697. 10.1111/j.1471-4159.1989.tb11759.x.View ArticlePubMedGoogle Scholar
- Choi J, Rees HD, Weintraub ST, Levey AI, Chin LS, Li L: Oxidative modifications and aggregation of Cu,Zn-superoxide dismutase associated with Alzheimer and Parkinson disease. Journal of Biological Chemistry. 2005, 280: 11648-11655. 10.1074/jbc.M414327200.View ArticlePubMedGoogle Scholar
- Radunovic A, Porto WG, Zeman S, Leigh PN: Increased mitochondrial superoxide dismutase activity in Parkinson's disease but not amyotrophic lateral sclerosis motor cortex. Neuroscience Letters. 1997, 239: 105-108. 10.1016/S0304-3940(97)00905-1.View ArticlePubMedGoogle Scholar
- Ernster L, Dallner G: Biochemical, physiological and medical aspects of ubiquinone function. Annals of Neurology. 1995, 42: 261-264.Google Scholar
- Shults CQ, Haas RH, Passov D, Beal MF: Coenzyme Q10 levels correlate with the activities of complexes I and II/III mitochondria from parkinsonian and nonparkinsonian patients. Annals of Neurology. 1997, 42: 261-264. 10.1002/ana.410420221.View ArticlePubMedGoogle Scholar
- Gotz ME, Gerstner A, Harth R, Dirr A, Janetzky B, Kuhn W, Riederer P, Gerlach M: Altered redox state of platelet coenzyme Q10 in Parkinson's disease. Journal of Neural Transmission. 2000, 107: 41-48. 10.1007/s007020050003.View ArticlePubMedGoogle Scholar
- Zheng X, Shoffner JM, Voljavec AS, Wallace DC: Evaluation of procedures for assaying oxidative phosphorylation enzyme activies in mitochondrial myopathy muscle biopsies. Biochimica Biophysica Acta. 1990, 101: 1-10.View ArticleGoogle Scholar
- Lowry OH, Rosebrough NJ, Farr AL, Randall RS: Protein measurement with the Folin phenlo reagent. Journal of Biological Chemistry. 1951, 193: 265-271.PubMedGoogle Scholar
- Flohé L, Günzler W: Assays of glutathione peroxidase. Methods in Enzymology. 1984, 105: 114-121. full_text.View ArticlePubMedGoogle Scholar
- Aebi H: Catalase in vitro. Methods in Enzymology. 1984, 105: 121-126. full_text.View ArticlePubMedGoogle Scholar
- Spitz DR, Oberley LW: An assay for superoxide dismutase activity in mammalian tissue homogenates. Analitical Biochemistry. 1989, 179: 8-18. 10.1016/0003-2697(89)90192-9.View ArticleGoogle Scholar
- Langedijk J, Ubbink JB, Vermaak WJH: Measurement of the ratio between the reduced and oxidized forms of coenzyme Q10 in human plasma as a possible marker of oxidative stress. Journal of Lipid Research. 1996, 37: 67-75.Google Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2377/10/95/prepub
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