Ubiquinone (coenzyme q10) and mitochondria in oxidative stress of parkinson's disease.

Parkinson's disease is the second most common neurodegenerative disorder after Alzheimer's disease affecting approximately1% of the population older than 50 years. There is a worldwide increase in disease prevalence due to the increasing age of human populations. A definitive neuropathological diagnosis of Parkinson's disease requires loss of dopaminergic neurons in the substantia nigra and related brain stem nuclei, and the presence of Lewy bodies in remaining nerve cells. The contribution of genetic factors to the pathogenesis of Parkinson's disease is increasingly being recognized. A point mutation which is sufficient to cause a rare autosomal dominant form of the disorder has been recently identified in the alpha-synuclein gene on chromosome 4 in the much more common sporadic, or 'idiopathic' form of Parkinson's disease, and a defect of complex I of the mitochondrial respiratory chain was confirmed at the biochemical level. Disease specificity of this defect has been demonstrated for the parkinsonian substantia nigra. These findings and the observation that the neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP), which causes a Parkinson-like syndrome in humans, acts via inhibition of complex I have triggered research interest in the mitochondrial genetics of Parkinson's disease. Oxidative phosphorylation consists of five protein-lipid enzyme complexes located in the mitochondrial inner membrane that contain flavins (FMN, FAD), quinoid compounds (coenzyme Q10, CoQ10) and transition metal compounds (iron-sulfur clusters, hemes, protein-bound copper). These enzymes are designated complex I (NADH:ubiquinone oxidoreductase, EC 1.6. 5.3), complex II (succinate:ubiquinone oxidoreductase, EC 1.3.5.1), complex III (ubiquinol:ferrocytochrome c oxidoreductase, EC 1.10.2.2), complex IV (ferrocytochrome c:oxygen oxidoreductase or cytochrome c oxidase, EC 1.9.3.1), and complex V (ATP synthase, EC 3.6.1.34). A defect in mitochondrial oxidative phosphorylation, in terms of a reduction in the activity of NADH CoQ reductase (complex I) has been reported in the striatum of patients with Parkinson's disease. The reduction in the activity of complex I is found in the substantia nigra, but not in other areas of the brain, such as globus pallidus or cerebral cortex. Therefore, the specificity of mitochondrial impairment may play a role in the degeneration of nigrostriatal dopaminergic neurons. This view is supported by the fact that MPTP generating 1-methyl-4-phenylpyridine (MPP(+)) destroys dopaminergic neurons in the substantia nigra. Although the serum levels of CoQ10 is normal in patients with Parkinson's disease, CoQ10 is able to attenuate the MPTP-induced loss of striatal dopaminergic neurons.

Hemichrome formation, lipid peroxidation, enzyme inactivation and protein degradation as indexes of oxidative damage in homogenates of chicken kidney and liver.

The change in relative hemichrome formation (RHF) was investigated as a potential marker of oxidative damage in kidney and liver homogenates prepared from chicks fed diets deficient or adequate in vitamin E. RHF gave an earlier indication of oxidative damage in tissue homogenates than the formation of thiobarbituric acid reactive substances (TBARS) or decrease in glutathione peroxidase activity (GPXA). RHF correlated significantly with both TBARS and GPXA. The correlations were 0.64 (P < 0.0001) and -0.57 (P = 0.0002) in kidney homogenates and 0.53 (P = 0.0006) and -0.71 (P < 0.0001) in liver homogenates. The correlation between RHF and the sum of TBARS and GPXA was also highly significant in both kidney and liver homogenates.

Ferrous-iron-induced oxidation in chicken liver slices as measured by hemichrome formation and thiobarbituric acid-reactive substances: effects of dietary vitamin E and beta-carotene.

Hemichrome formation in chicken liver slices was determined by employing a Heme Protein Spectra Analysis Program (HPSAP) on the visible spectrum of the liver tissue. Relative hemichrome formation (RHF) in liver tissue exposed to ferrous iron for 1 h at 37 degrees C could be predicted according to the general catalytic equation RHF = k.[Fe2+]/(Ap + [Fe2+]), with k = 132 +/- 30, where the factor Ap represents the additive antioxidative potential in the liver tissue. RHF in Fe2+ exposed liver slices incubated at 37 degrees C for 1 h correlated significantly with formation of thiobarbituric acid-reactive substances (TBARS) (r = .77, P < .0001). RHF was found to decrease significantly with increasing vitamin E concentration in liver tissue exposed to ferrous iron (1 h, 37 degrees C). However, the influence of beta-carotene on RHF in ferrous-iron exposed liver slices (1 h, 37 degrees C) was less evident, as the concentration of Fe2+ was found to be decisive for whether beta-carotene acted as an antioxidant or a prooxidant under the conditions in question. Results in the liver slice model system regarding the effect of vitamin E and beta-carotene on iron overload were supported in a subsequent in vivo iron injection experiment with chicks. These observations indicate that RHF is a sensitive marker for ferrous-iron-induced oxidative damage in the present tissue slice system.

Protection by vitamin E, selenium, and beta-carotene against oxidative damage in rat liver slices and homogenate.

Male Sprague-Dawley (SD) rats were fed a vitamin E and selenium deficient diet and diets supplemented with vitamin E, selenium, beta-carotene, and a combination of the three. Tissue slices and homogenate of liver were incubated at 37 degrees C with and without the presence of prooxidants. The effect of vitamin E, selenium, beta-carotene, and the combination of the three antioxidants on the oxidative damage to rat liver tissue was studied by measuring the production of oxidized heme proteins in both tissue slices and homogenate during spontaneous and prooxidant-induced oxidation. The diet with the combination of all three antioxidants showed a strong protective effect against oxidative damage to heme proteins in contrast to the antioxidant-deficient diet. In general, diets with vitamin E, selenium, and beta-carotene were less effective than the combination of all three antioxidants. The protective effect of antioxidants on the heme protein oxidation was correlated with their inhibitory effect on lipid peroxidation measured as the production of thiobarbituric acid-reactive substance (TBARS). The protection of antioxidants on heme proteins was also dependent on the type of oxidation inducer. Possible mechanisms of antioxidants against oxidation in liver tissues are discussed.