Biofactors - Volume 9, issue 2-4

Authors: Navarro, Francisco | Arroyo, Antonio | Martín, Sergio F. | Bello, Rosario I. | de Cabo, Rafael | Burgess, John R. | Navas, Plácido | Villalba, José M.

Article Type: Research Article

Abstract: We have studied the effects of dietary depletion of vitamin E and selenium on endogenous ubiquinone‐dependent antioxidant system. Deficiency induced an increase in both coenzyme Q_{9} and Q_{10} in liver tissue, reaching a maximum between 4 and 7 weeks of deficient diet consumption. Cytochrome b_{5} reductase polypeptide was also enriched in membranes after 5 weeks of deficient diet consumption. Substantial DT‐diaphorase activity was found in deficient, but not in control plasma membranes. Deficient membranes were very sensitive to lipid peroxidation, although a great protection was observed after incubation with NAD(P)H. Our results show that …liver cells can boost endogenous ubiquinone‐dependent protective mechanisms in response to deficiency in vitamin E and selenium. Show more

Citation: Biofactors, vol. 9, no. 2-4, pp. 163-170, 1999

Authors: López‐Lluch, G. | Barroso, M.P. | Martín, S.F. | Fernández‐Ayala, D.J.M. | Gómez‐Díaz, C. | Villalba, J.M. | Navas, P.

Article Type: Research Article

Abstract: Serum withdrawal is a model to study the mechanisms involved in the induction of apoptosis caused by mild oxidative stress. Apoptosis induced by growth factors removal was prevented by the external addition of antioxidants such as ascorbate, \alpha ‐tocopherol and coenzyme Q (CoQ). CoQ is a lipophilic antioxidant which prevents oxidative stress and participates in the regeneration of \alpha ‐tocopherol and ascorbate in the plasma membrane. We have found an inverse relationship between CoQ content in plasma membrane and lipid peroxidation rates in leukaemic cells. CoQ_{10} addition to serum‐free culture media prevented both lipid peroxidation and …cell death. Also, CoQ_{10} addition decreased ceramide release after serum withdrawal by inhibition of magnesium‐dependent plasma membrane neutral‐sphingomyelinase. Moreover, CoQ_{10} addition partially blocked activation of CPP32/caspase‐3. These results suggest CoQ of the plasma membrane as a regulator of initiation phase of oxidative stress‐mediated serum withdrawal‐induced apoptosis. Show more

Citation: Biofactors, vol. 9, no. 2-4, pp. 171-177, 1999

Authors: Morré, D. James | Pogue, Rhea | Morré, Dorothy M.

Article Type: Research Article

Abstract: A multifunctional cell surface protein with NADH oxidase (NOX) activity and capable of oxidizing hydroquinones is located at the exterior of the cell and is shed in soluble form into sera. The oxidase appears to function as a terminal oxidase of a trans plasma membrane electron transport chain consisting of a NAD(P)H‐ubiquinone reductase at the cytosolic membrane surface, possibly a b ‐type cytochrome, ubiquinone and the oxidase. Hyperactivity or conditions that interrupt ordered 2H^{+} + 2e^{-} transport from NAD(P)H or hydroquinone to molecular oxygen and other acceptors at the external cell surface may …result in the generation of superoxide. The latter may serve to propagate aging‐related redox changes both to adjacent cells and circulating blood components. A circulating NOX activity form associated with aging and the reduction of cytochrome c by sera of aged patients that is partially inhibited by ubiquinone are described. Show more

Citation: Biofactors, vol. 9, no. 2-4, pp. 179-187, 1999

Authors: Kishi, Takeo | Takahashi, Takayuki | Usui, Akinori | Hashizume, Naoko | Okamoto, Tadashi

Article Type: Research Article

Abstract: Cellular ubiquinone (UQ) is expected to act as an endogenous antioxidant against oxidative stress. To confirm this, UQ‐reductases which are necessary to regenerate ubiquinol (UQH_{2} ) were investigated in rat tissue, and a novel NADPH‐dependent UQ (NADPH‐UQ) reductase was found in cytosol. The cytosolic NADPH‐UQ reductase activity accounted for more than 80% of UQ‐10 reduction by the rat liver homogenate in the presence of NADPH. Furthermore, the NADPH‐UQ reductase activities in various tissues were correlated to the redox states of UQ in the corresponding tissues. Rat liver cytosol with NADPH protected lecithin liposomes containing UQ‐10, as well as UQH_{2} …‐10 from AMVN (2,2' ‐azobis(2,4‐dimethyl‐valeronitrile))‐induced lipid peroxidation. The enzyme purified from rat liver cytosol, reduced UQ‐10 in lecithin liposomes at approximately the same rate as did cytosol. These results supported that cytosolic NADPH‐UQ reductase is the enzyme responsible for nonmitochondrial UQ reduction acting as an endogenous antioxidant against oxidative stress. The antioxidant role of the UQ redox cycle and NADPH‐UQ reductase was discussed in relation to other cellular NADPH‐dependent antioxidant enzymes. Show more

Keywords: Ubiquinone, quinone reductase, NADPH dehydrogenase, antioxidant, liver

Citation: Biofactors, vol. 9, no. 2-4, pp. 189-197, 1999

Authors: Lass, Achim | Kwong, Linda | Sohal, Rajindar S.

Article Type: Research Article

Abstract: The main objective of this study was to determine the nature of the relationship between aging and mitochondrial coenzyme Q (CoQ) content. Mitochondria in the heart, skeletal muscle, kidney and brain of the mouse varied in both the amount of total CoQ (CoQ_{9}+{} CoQ_{10} ) content as well as in the ratio of the CoQ_{9} to CoQ_{10} . CoQ content declined with age only in the skeletal muscle. Caloric restriction (CR) resulted in an increase in the amount of CoQ_{9} in skeletal muscle mitochondria. This effect was partially reversible upon termination of the …caloric restriction regimen. Results suggest that a decrease in mitochondrial CoQ content is an integral aspect of aging in skeletal muscle. Show more

Citation: Biofactors, vol. 9, no. 2-4, pp. 199-205, 1999

Authors: Thomas, Shane R. | Witting, Paul K. | Stocker, Roland

Article Type: Research Article

Abstract: Substantial evidence implicates oxidative modification of low density lipoprotein (LDL) as an important event contributing to atherogenesis. As a result, the elucidation of the molecular mechanisms by which LDL is oxidized and how such oxidation is prevented by antioxidants has been a significant research focus. Studies on the antioxidation of LDL lipids have focused primarily on \alpha ‐tocopherol (\alpha ‐TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid‐soluble antioxidant in extracts prepared from human LDL. In addition to \alpha ‐TOH, plasma LDL also contains low levels of ubiquinol‐10 (CoQ_{10} …H_{2} ; the reduced form of coenzyme Q_{10} ). Recent studies have shown that in oxidizing plasma lipoproteins \alpha ‐TOH can exhibit anti‐ or pro‐oxidant activities for the lipoprotein’s lipids exposed to a vast array of oxidants. This article reviews the molecular action of \alpha ‐TOH in LDL undergoing “mild” radical‐initiated lipid peroxidation, and discusses how small levels of CoQ_{10} H_{2} can represent an efficient antioxidant defence for lipoprotein lipids. We also comment on the levels \alpha ‐TOH, CoQ_{10} H_{2} and lipid oxidation products in the intima of patients with coronary artery disease and report on preliminary studies examining the effect of coenzyme Q_{10} supplementation on atherogenesis in apolipoprotein E knockout mice. Show more

Citation: Biofactors, vol. 9, no. 2-4, pp. 207-224, 1999

Authors: Kontush, Anatol | Schippling, Sven | Spranger, Torsten | Beisiegel, Ulrike

Article Type: Research Article

Abstract: Ubiquinol‐10 and ubiquinone‐10 were measured in plasma of patients with several pathologies known to be associated with increased oxidative stress. Plasma ubiquinol‐10, expressed as a percentage of total ubiquinol‐10 + ubiquinone‐10, was found to be significantly lower in hyperlipidaemic patients and in patients with liver diseases than in age‐matched control subjects. In contrast, no decrease in ubiquinol‐10 was detected in plasma of patients with coronary heart disease and Alzheimer’s disease. Except for ubiquinol‐10, no other lipophilic antioxidant was found to be decreased in patients with liver diseases. These data suggest that the level of ubiquinol‐10 in human plasma …may serve as a marker for liver dysfunction, reflecting its diminished reduction by the liver rather than increased consumption by oxidants. Show more

Keywords: Ubiquinol‐10, oxidation, antioxidants, atherosclerosis, hyperlipidaemia, coronary heart disease, Alzheimer’s disease, liver diseases

Citation: Biofactors, vol. 9, no. 2-4, pp. 225-229, 1999

Authors: Tomasetti, Marco | Alleva, Renata | Solenghi, Maria Diana | Littarru, Gian Paolo

Article Type: Research Article

Abstract: Total CoQ_{10} levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ_{10} and whole blood CoQ_{10} . CoQ_{10} is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL‐chol/CoQ_{10} ratio and the total‐chol/HDL‐chol ratio, which is usually considered a risk factor for atherosclerosis. The …proportion of CoQ_{10} carried by LDL was 58 \pm 10%, while the amount carried by HDL was 26 \pm 8%. In VLDL + IDL CoQ_{10} was 16 \pm 8%. The content of CoQ_{10} in single classes of lipoproteins is strictly correlated with CoQ_{10} plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ_{10} plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ_{10} /chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ_{10} /triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients. Show more

Citation: Biofactors, vol. 9, no. 2-4, pp. 231-240, 1999

Authors: Yamamoto, Yorihiro | Yamashita, Satoshi

Article Type: Research Article

Abstract: To assess the degree of oxidative stress, we measured plasma ubiquinone‐10 percentage (%CoQ‐10) in total amounts of ubiquinone‐10 in patients with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma, and in age‐matched control subjects. %CoQ‐10 values were 12.9 \pm 10.3 (n={} 28), 10.6 \pm 6.8 (n={} 28), 18.9 \pm 11.1 (n={} 20), and 6.4 \pm 3.3 (n={} 16), respectively, showing a significant increase in oxidative stress in patient groups as compared to control subjects. There were no differences in total amounts of ubiquinone‐10 and ubiquinol‐10 among the four …groups. We next measured %CoQ‐10 in plasmas obtained from nine patients treated with percutaneous transluminal coronary angioplasty (PTCA). Plasmas were collected when hospitalized, and at the time (0, 4, 8, 12, 16, and 20 hr, and 1, 2, 3, 4, and 7 days) after the PTCA. %CoQ‐10 values before and right after PTCA were 9.9 \pm 2.8 and 11.4 \pm 2.0, respectively, reached a maximum (20–45) at 1 or 2 days later, and decreased to 7.9 \pm 2.7 at 7 days after PTCA, indicating an increase in oxidative stress in patients during coronary reperfusion. Show more

Keywords: Ubiquinol, ubiquinone, oxidative stress, hepatitis, cirrhosis, hepatoma, percutaneous transluminal coronary angioplasty (PTCA)

Citation: Biofactors, vol. 9, no. 2-4, pp. 241-246, 1999

Authors: Rustin, Pierre | Munnich, Arnold | Rötig, Agnès

Article Type: Research Article

Citation: Biofactors, vol. 9, no. 2-4, pp. 247-251, 1999