Biofactors - Volume 18, issue 1-4

Authors: Zita, Čestmír | Overvad, Kim | Mortensen, Svend Aage | Dan Sindberg, Christian | Moesgaard, Sven | Hunter, Douglas A.

Article Type: Research Article

Abstract: Serum coenzyme Q_{10} (Q_{10} ) concentrations were evaluated in healthy male volunteers supplemented with 30 mg or 100 mg Q_{10} or placebo as a single daily dose for two months in a randomised, double-blind, placebo-controlled study. Median baseline serum Q_{10} concentration in 99 men was 1.26 mg/l (10%, 90% fractiles: 0.82, 1.83). Baseline serum Q_{10} concentration did not depend on age, while borderline significant positive …associations were found for body weight and smoking 1–10 cigarettes/d. Supplementation with 30 mg or 100 mg Q_{10} resulted in median increases in serum Q_{10} concentration of 0.55 mg/l and 1.36 mg/l, respectively, compared with a median decrease of 0.23 mg/l with placebo. The changes in the Q_{10} groups were significantly different from that in the placebo group, and the increase in the 100 mg Q_{10} group was significantly greater than that in the 30~mg Q_{10} group. The change in serum Q_{10} concentration in the Q_{10} groups did not depend on baseline serum _{10} concentration, age, or body weight. Show more

Keywords: coenzyme Q_{10}, ubiquinone, absorption, dose-response, double-blind trial

Citation: BioFactors, vol. 18, no. 1-4, pp. 185-193, 2003

Authors: Galati, Giuseppe | O'Brien, Peter J.

Article Type: Research Article

Abstract: Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and serves as an electron donor and acceptor in mitochondrial energy-linked respiration. CoQ_{1} was shown to prevent ROS formation and cell death in complex 1 inhibited cells. Low concentrations of capsaicin like CoQ_{1} inhibited ROS formation but CoQ_{1} was more effective at restoring the mitochondrial membrane potential collapse caused by complex 1 inhibitors such …as rotenone. At low concentrations, capsaicin acts as a CoQ mimic by protecting against rotenone induced ROS formation and mitochondrial membrane potential collapse. Lipid peroxidation in isolated rat hepatocytes induced by cumene hydroperoxide and chloroacetaldehyde was also prevented. At higher concentrations, capsaicin and CoQ_{1} became cytotoxic. Hep G2 cells were more susceptible than hepatocytes. The cytotoxic mechanism for both capsaicin and CoQ_{1} was shown to involve a collapse of the mitochondrial membrane potential, however, only capsaicin caused ROS formation. The capsaicin side chain was required for capsaicin induced cytotoxicity. The anticancer properties of CoQ_{1} and capsaicin should prove useful for inducing tumor cell apoptosis. Show more

Keywords: coenzyme Q, capsaicin, hepatocytes, Hep G2 cells, mitochondria, anticancer

Citation: BioFactors, vol. 18, no. 1-4, pp. 195-205, 2003

Authors: S. Chan, Tom | O'Brien, Peter J.

Article Type: Research Article

Abstract: Previous studies on the metabolism of coenyzme Q (CoQ) have focused on products found in the urine, bile or feces. However, the metabolites found in these samples were end products from a multitude of catabolic processes which did not necessarily reflect CoQ intracellular metabolism (e.g. in the liver, the major site of CoQ synthesis or metabolism). Using isolated rat hepatocytes, we have found that the sulfation of coenzyme Q_{1} (CoQ_{1} ) was the …initial and dominant step following its reduction to the hydroquinone. This metabolic process is important as conjugation may occur on the hydroquinone metabolites of any coenzyme_{10} scission product retaining the quinone ring. By using rat liver cytosol, we were able to identify the monosulfated metabolite of CoQ_{1} . The CoQ_{1} sulfate conjugate was identified by mass spectrometry followed by tandem mass spectrometry. The rate of formation of the CoQ_{1} sulfate conjugate was markedly increased by the addition of NADH and was prevented by dicumarol, a DT-diaphorase (NQO_{1} ) inhibitor. CoQ_{1} sulfate conjugate formation catalysed by cytosol was inhibited by the sulfotransferase 1A (SULT1A) inhibitor, pentachlorophenol (PCP) suggesting that sulfation was carried out by the SULT 1A isoform. CoQ_{1} sulfation in isolated hepatocytes and inversely CoQ_{1} hydroquinone formation were dependent on the concentration of inorganic sulfate in the media. Intracellular sulfation also decreased CoQ_{1} antioxidant and cytoprotective activity towards cumene hydroperoxide (CHP) induced cell death. Sulfotransferases may therefore play a significant role in endogenous CoQ metabolism following its degradation to short chain products. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 207-218, 2003

Authors: Gómez-Díaz, Consuelo | I. Bello, Rosario | López-Lluch, Guillermo | Forthoffer, Nathalie | Navas, Plácido | Villalba, José M.

Article Type: Research Article

Abstract: We have previously shown that inhibition of NAD(P)H:quinone acceptor oxidoreductase 1 with dicoumarol decreases growth and viability of HL-60 cells in the absence of serum. Here we demonstrate that culturing HL-60 cells in serum-free medium in the presence of dicoumarol results in a significant potentiation of apoptosis. However, when cells were preincubated for 24 h without serum before they were treated with dicoumarol, the effect of the inhibitor on cell growth and death was much lower. …We have investigated cellular changes induced in HL-60 cells by removal of serum that could account for protection against the effects of dicoumarol. Serum removal induced significant increases of NAD(P)H:quinone acceptor oxidoreductase 1, particularly at 32 h after serum withdrawal. Total amounts of ubiquinone in cells were unchanged but, its reduction state paralleled the observed increase in quinone reductase activity. Levels of the antiapoptotic protein Bcl-2 were also significantly increased after serum removal. Our results indicate that removal of serum evokes an antioxidant protective response that make HL-60 cells less sensitive to cell death induced by inhibition of NAD(P)H:quinone acceptor oxidoreductase 1 with dicoumarol. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 219-228, 2003

Authors: Saiki, Ryoichi | Ogiyama, Yuki | Kainou, Tomohiro | Nishi, Tomoko | Matsuda, Hideyuki | Kawamukai, Makoto

Article Type: Research Article

Abstract: We previously constructed two Schizosaccahromyces pombe ubiquinone-10 (or Coenzyme Q_{10} ) less mutants, which are either defective for decaprenyl diphosphate synthase or p-hydroxybenzoate polyprenyl diphosphate transferase. To further confirm the roles of ubiquinone in S. pombe, we examined the phenotype of the abc1Sp (coq8Sp) mutant, which is highly speculated to be defective in ubiquinone biosynthesis. We show here that the abc1Sp defective strain did not produce UQ-10 and could not grow …on minimal medium. The abc1Sp-deficient strain required supplementation with antioxidants such as cysteine or glutathione to grow on minimal medium. In support of the antioxidant function of ubiquinone, the abc1Sp-deficient strain is sensitive to H_{2} O_{2} and Cu^{2+} . In addition, expression of the stress inducible ctt1 gene was much induced in the ubiquinone less mutant than wild type. Interestingly, we also found that the abc1-deficient strain as well as other ubiquinone less mutants produced a significant amount of H_{2} S, which suggests that oxidation of sulfide by ubiquinone may be an important pathway for sulfur metabolism in S. pombe. Thus, analysis of the phenotypes of S. pombe ubiquinone less mutants clearly demonstrate that ubiquinone has multiple functions in the cell apart from being an integral component of the electron transfer system. Show more

Keywords: fission yeast, ubiquinone-10, antioxidant, sulfide, coq8

Citation: BioFactors, vol. 18, no. 1-4, pp. 229-235, 2003

Authors: Rodríguez-Aguilera, Juan C. | Asencio, Claudio | Ruiz-Ferrer, Macarena | Vela, Jordana | Navas, Plácido

Article Type: Research Article

Abstract: Ubiquinone (coenzyme Q, Q) is an essential lipid electron carrier in the mitochondria respiratory chain, and also functions as antioxidant and participates as a cofactor of mitochondrial uncoupling proteins. Caernorhabditis elegans synthesize Q_9 , but both dietary Q_8 intake and endogenous Q_9 biosynthesis determine Q balance. Thus, it is of current interest to know the regulatory mechanisms of Q_9 biosynthesis in this nematode. Here we …review results that leaded to identification of genes involved in Q_9 biosynthesis in this nematode using the RNA interference technology. C. elegans coq genes were silenced and depletion of Q content was observed, indicating that the genes related here participate in Q_9 biosynthesis. Silenced populations showed an extension of adult life span, probably by the decrease of endogenous oxidative stress produced in mitochondria. We also report the heterologous complementation of C. elegans coq-5 and coq-7 genes in their homologue yeast coq null mutants, leading to restore its ability to growth in non-fermentable sugars. These complemented yeast strains accumulated Q_6 but also the intermediate demethoxy-Q_6 . These findings support the conservative functional homology of these genes. Show more

Keywords: coenzyme Q, aging, RNAi, superoxide, mitochondria

Citation: BioFactors, vol. 18, no. 1-4, pp. 237-244, 2003

Authors: Korkina, Ludmila | Deeva, Irina | Ibragimova, Galina | Shakula, Alexander | Luci, Antonio | De Luca, Chiara

Article Type: Research Article

Abstract: The manual workers of the gas-and-oil extraction industry are exposed to hostile environmental and occupational conditions, resulting in elevated mortality and disability, due to chronic neurological and cardiovascular diseases. We evaluated the degree of oxidative stress, often associated with these pathological features, in the blood of manual and office employees of Russian Siberian extraction plants, and their psycho-physiological conditions. Results showed increased levels of spontaneous (p < 0.05) and PMA-activated (p < …0.01) luminol-dependent chemiluminescence (LDCL) in the white blood cells (WBC), and decreased peroxynitrite levels (p < 0.05) in the group of manual workers, and less markedly in the clerks and technicians working on spot, vs. a control group of city clerks. Superoxide release by WBC, and plasma/WBC membrane ubiquinol levels did not display major differences in the three groups. A relevant percentage of manual/office workers of extraction platforms presented impaired cardiovascular and neurological functions. The short term administration of a nutraceutical formulation based on coenzyme_{10} , vitamin E, selenium, methionine and phospholipids led to significant improvement of cardiovascular parameters and psycho-emotional status, consistent with the normalization of LDCL and peroxynitrite production by WBC, with a good compliance to treatment confirmed by the increased blood levels of ubiquinol. Show more

Keywords: petrochemical workers, occupational diseases, oxidative stress, antioxidants

Citation: BioFactors, vol. 18, no. 1-4, pp. 245-254, 2003

Authors: Korkina, Ludmila | Suprun, Maxim | Petrova, Anna | Mikhal'chik, Elena | Luci, Antonio | De Luca, Chiara

Article Type: Research Article

Abstract: Oxygen/nitrogen reactive species (ROS/RNS) are currently implicated in the pathogenesis of ulcerative colitis, drawing attention on the potential prophylactic and healing properties of antioxidants, scavengers, chelators. We evaluated the possible protective/curative effects of a natural antioxidant preparation based on Aloe vera and ubiquinol, against intestinal inflammation, lesions, and pathological alterations of the intestinal electrophysiological activity and motility, in a rat model of DSS-induced colitis. 5% dextrane sulfate (DDS) (3 days), followed by …1% DSS (4 days) was administered in drinking water. The antioxidant formulation (25 mg/kg) was delivered with a pre-treatment protocol, or simultaneously or post-colitis induction. Spontaneous and acetylcholine-stimulated electrical activity were impaired in the small intestine and in distal colon, upon exposure to DSS only. Severe inflammation occurred, with increased myeloperoxidase activity, and significant alterations of the oxidant/antioxidant status in colonic tissue and peritoneal cells. Lipoperoxidation, superoxide production, glutathione peroxidase and glutathione-S-transferase activities, and reduced glutathione content increased, whilst superoxide dismutase and catalase activities were sharply suppressed in colon tissue. ROS/RNS formation in peritoneal cells was strongly inhibited. Inflammation, electrical/mechanical impairment in the gut, and a great majority of oxidative stress parameters were improved substantially by pre-treatment with the antioxidant preparation, but not by simultaneous administration or post-treatment. Show more

Keywords: ulcerative colitis, Crohn's disease, inflammatory bowel disease, free radicals, antioxidants

Citation: BioFactors, vol. 18, no. 1-4, pp. 255-264, 2003

Authors: Quiles, J.L. | Farquharson, A.J. | Ramírez-Tortosa, M.C. | Grant, I. | Milne, L. | Huertas, J.R. | Battino, M. | Mataix, J. | Wahle, K.W.J.

Article Type: Research Article

Abstract: The aim of this study was to investigate the role of coenzyme Q on the mRNA abundance of PHGPx and the reactive oxygen species (ROS) production in two different cell lines from human prostate, a line of non cancer cells (PNT2) and a line of cancer cells (PC3). Results showed that malignant cells markedly differ in their response to coenzyme Q compared to non-malignant cells, with no changes in PHGPx expression and greater ROS production. Furthermore coenzyme Q …supplementation significantly lowered cell growth of the PC3 cancer line without affecting the PNT2. If these results are confirmed with additional experiments, it could represent a novel and interesting approach on the biomedical use of coenzyme Q_{10} in cancer therapy. Show more

Keywords: ubiquinone, prostate cancer, antioxidants, gene expression

Citation: BioFactors, vol. 18, no. 1-4, pp. 265-270, 2003

Authors: Battino, Maurizio | Bompadre, Stefano | Leone, Luciana | Pugnaloni, Armanda | Rubini, Corrado | Ferreiro, Maria Soledad | Gallardo, Isabel | Bullon, Pedro

Article Type: Research Article

Abstract: Cyclosporine A (CsA) plays a pivotal role in controlling Ca^{2+} movement in the cell modulating also the mitochondrial permeability transition pore. We investigated if chronic administration of CsA may have some effects on the lipophilic and hydrophilic antioxidant pattern of rat liver mitochondria and on their morphological structure. It seems that CsA administration does not statistically affect the redox status of the antioxidants investigated and their amounts (vitamin E, CoQ_9 …, CoQ_{10} , glutathione,uric acid and ascorbic acid) despite the variety of effects that this treatment produces at physiological and morphological levels. However, some kind of derangement could occur in the liver biochemical machinery since CsA treatment induces a markedly increased variability in antioxidant contents. Show more

Keywords: coenzyme Q, Vitamin E, rat liver mitochondria, GSH, uric acid, ascorbic acid

Citation: BioFactors, vol. 18, no. 1-4, pp. 271-275, 2003