Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice

Beal, M. Flint; Matthews, Russell T.; Tieleman, A.A.; Shults, Clifford W.

doi:10.1016/s0006-8993(97)01192-x

Cited by 237 publications

(146 citation statements)

References 33 publications

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“…Although early trials with creatine, coenzyme Q10, and other antioxidant supplements have been disappointing (51), they share the hypothesis that oxidant stress exacerbates the symptoms and progression of PD. Coenzyme Q10 is an electron acceptor for complexes I and II that appears compromised in PD patients (64,106) and is neuroprotective in animal models of PD (6,7). Creatine is a substrate for ATP production that can both improve mitochondrial efficiency and reduce oxidant stress by buffering fluctuations in cellular energy production (64).…”

Section: Surmeier Et Almentioning

confidence: 99%

The Origins of Oxidant Stress in Parkinson's Disease and Therapeutic Strategies

Surmeier

Guzmán

Sánchez-Padilla

et al. 2011

Antioxidants & Redox Signaling

135

109

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Parkinson's disease (PD) is a major world-wide health problem afflicting millions of the aged population. Factors that act on most or all cell types (pan-cellular factors), particularly genetic mutations and environmental toxins, have dominated public discussions of disease etiology. Although there is compelling evidence supporting an association between disease risk and these factors, the pattern of neuronal pathology and cell loss is difficult to explain without cell-specific factors. This article focuses on recent studies showing that the neurons at greatest risk in PD-substantia nigra pars compacta dopamine neurons-have a distinctive physiological phenotype that could contribute to their vulnerability. The opening of L-type calcium channels during autonomous pacemaking results in sustained calcium entry into the cytoplasm of substantia nigra pars compacta dopamine neurons, resulting in elevated mitochondrial oxidant stress and susceptibility to toxins used to create animal models of PD. This cellspecific stress could increase the negative consequences of pan-cellular factors that broadly challenge either mitochondrial or proteostatic competence. The availability of well-tolerated, orally deliverable antagonists for L-type calcium channels points to a novel neuroprotective strategy that could complement current attempts to boost mitochondrial function in the early stages of the disease.

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Section: Surmeier Et Almentioning

confidence: 99%

The Origins of Oxidant Stress in Parkinson's Disease and Therapeutic Strategies

Surmeier

Guzmán

Sánchez-Padilla

et al. 2011

Antioxidants & Redox Signaling

135

109

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“…Numerous reports have suggested that ubiquinone (coenzyme Q 10 ) may have beneficial effects in neurodegenerative disorders (1)(2)(3)(4)(5)(6). However, it is difficult to utilize ubiquinone in in vitro experiments because of its high level of hydrophobicity.…”

mentioning

confidence: 99%

“…In this study, the effects of decylubiquinone on the activities of a number of electron transport chain (ETC) 2 components, complexes I (EC 1.6.5.3), I/III (EC 1.6.99.3), II/III (EC 1.3.5.1 ϩ 1.10.2.2), and III (EC 1.10.2.2), in rat brain synaptosomes were examined. In addition, the effect of decylubiquinone on synaptosomal oxygen consumption, during titration with mitochondrial inhibitors, was investigated.…”

mentioning

confidence: 99%

Decylubiquinone Increases Mitochondrial Function in Synaptosomes

Telford

Kilbride

Davey

2010

Journal of Biological Chemistry

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The effects of decylubiquinone, a ubiquinone analogue, on mitochondrial function and inhibition thresholds of the electron transport chain enzyme complexes in synaptosomes were investigated. Decylubiquinone increased complex I/III and complex II/III activities by 64 and 80%, respectively, and attenuated reductions in oxygen consumption at high concentrations of the complex III inhibitor myxothiazol. During inhibition of complex I, decylubiquinone attenuated reductions in synaptosomal oxygen respiration rates, as seen in the complex I inhibition threshold. Decylubiquinone increased the inhibition thresholds of complex I/III, complex II/III, and complex III over oxygen consumption in the nerve terminal by 25-50%, when myxothiazol was used to inhibit complex III. These results imply that decylubiquinone increases mitochondrial function in the nerve terminal during complex I or III inhibition. The potential benefits of decylubiquinone in diseases where complex I, I/III, II/III, or III activities are deficient are discussed.Numerous reports have suggested that ubiquinone (coenzyme Q 10 ) may have beneficial effects in neurodegenerative disorders (1-6). However, it is difficult to utilize ubiquinone in in vitro experiments because of its high level of hydrophobicity. Therefore, the beneficial effects of synthesized ubiquinone analogues, such as decylubiquinone (2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone), are under investigation. Decylubiquinone is an exogenous, hydrophobic quinone that has a 10-carbon side chain with a methyl group at the end and can travel into mitochondrial membranes unaided (7). Decylubiquinone accepts electrons from complex I and is reduced to decylubiquinol, which subsequently transfers electrons to complex III. Studies on the effect of decylubiquinone on the steadystate kinetics of complex I in bovine heart mitochondria showed that the binding of decylubiquinone induced a conformational change in the shape of the binding site, which allows the binding of a quinone with a long isoprenoid side chain (8). Decylubiquinone may be used favorably as an alternative to coenzyme Q 1 because the interaction of decylubiquinone with complex I is more similar to that between endogenous ubiquinone and complex I than between coenzyme Q 1 and complex I and because coenzyme Q 1 is not as efficient at activating complex I activity as decylubiquinone (9).In this study, the effects of decylubiquinone on the activities of a number of electron transport chain (ETC) 2 components, complexes I (EC 1.6.5.3), I/III (EC 1.6.99.3), II/III (EC 1.3.5.1 ϩ 1.10.2.2), and III (EC 1.10.2.2), in rat brain synaptosomes were examined. In addition, the effect of decylubiquinone on synaptosomal oxygen consumption, during titration with mitochondrial inhibitors, was investigated. Metabolic control analysis may be used to examine the spread of control among components in a system (10, 11), and the inhibition threshold is a useful parameter that describes mitochondrial function. The inhibition threshold is the level by which each co...

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“…Studies performed on patients with PD and on animal model of PD have demonstrated an increase in oxidative stress in substantia nigra including lipid peroxidation, production of free radicals (Dexter et al, 1989;Przedborski et al, 1996;Jenner, 1998;Chalimoniuk et al, 2004b), and decreased glutathione concentration (Sian et al, 1994;Beal, 1995;Beal et al, 1998;Bharath et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol Transfer Protein Expression Altered by Aging and Parkinson Disease

Chalimoniuk

Snoek²,

Adamczyk

et al. 2006

Cell Mol Neurobiol

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SUMMARY1. Phosphatidylinositol transfer proteins (PI-TP) are responsible for the transport of phosphatidylinositol (PI) and other phospholipids from endoplasmic reticulum to the other membranes and indirectly for lipid mediated signaling. Till now little is known about PITPs in brain aging and neurodegeneration. The aim of this study was to investigate expression of PI-TP in the brain during aging and in animal's model of Parkinson disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Moreover, in vitro, effect of 1-methyl-4-phenyl-pyridine cation (MPP + ) on PI-TP, tyrosine hydroxylase (TH) protein level, and viability of cells was investigated.2. Wistar rats 4, 24, and 36 months old and C57/BL mice and rat pheochromocytoma (PC12) cell line were used for the studies. Mice C57/BL received three injections of MPTP in saline at 2 h intervals in a total dose of 40 mg/kg and then after 3, 7, and 14 days they were used for the investigation. PC12 cells were treated with increasing concentration (50-300 µM) of MPP + for 24 h at 37 • C. The level of PI-TP α and β and TH were determined using Western Blot analysis.3. Our data indicated that PI-TP α and β level decreased in brain of 36 months old rat by 20% comparing to the control value (4 months old). In animal's model of PD, PI-TP α and β level was significantly lower by 85, 69, 64% in striatum at 3, 7, and 14 days after MPTP injection, respectively, compared to the control value. MPP + decreased PI-TP α and β , TH expression, and viability of PC12 cells in a dose-dependent manner. H 2 O 2 , menadione, and NO donor significantly decreased the PI-TP level and viability of PC12 cells.4. Our results indicate the lower protein expression of PI-TP α and β in aged brain and in PD and suggest that oxidative stress may be responsible for the alteration of PI-TP.

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Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice

Cited by 237 publications

References 33 publications

The Origins of Oxidant Stress in Parkinson's Disease and Therapeutic Strategies

The Origins of Oxidant Stress in Parkinson's Disease and Therapeutic Strategies

Decylubiquinone Increases Mitochondrial Function in Synaptosomes

Phosphatidylinositol Transfer Protein Expression Altered by Aging and Parkinson Disease

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