Biofactors - Volume 18, issue 1-4

Article Type: Other

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

Authors: Bianchi, Cristina | Fato, Romana | Genova, Maria Luisa | Castelli, Giovanna Parenti | Lenaz, Giorgio

Article Type: Research Article

Abstract: Metabolic flux control analysis of NADH oxidation in bovine heart submitochondrial particles revealed high flux control coefficients for both Complex I and Complex III, suggesting that the two enzymes are functionally associated as a single enzyme, with channelling of the common substrate, Coenzyme Q. This is in contrast with the more accepted view of a mobile diffusable Coenzyme Q pool between these enzymes. Dilution with phospholipids of a mitochondrial fraction enriched in Complexes I and III, …with consequent increased theoretical distance between complexes, determines adherence to pool behavior for Coenzyme Q, but only at dilution higher than 1:5 (protein:phospholipids), whereas, at lower phospholipid content, the turnover of NADH cytochrome c reductase is higher than expected by the pool equation. Show more

Keywords: mitochondria, Coenzyme Q pool, supercomplex, flux control, Complex I, Complex III

Citation: BioFactors, vol. 18, no. 1-4, pp. 3-9, 2003

Authors: Dallner, Gustav | Brismar, Kerstin | Chojnacki, Tadeusz | Swiezewska, Ewa

Article Type: Research Article

Abstract: All animal cells synthesize sufficient amounts of coenzyme Q (CoQ) and the cells also possess the capacity to metabolize the lipid. The main product of the metabolism is an intact ring with a short carboxylated side chain which glucuronidated in the liver and excreted mainly into the bile (Nakamura et al., Biofactors 9 (1999), 111–119). In other cells CoQ is phosphorylated, transferred into the blood and excreted through the urine. The biosynthesis of this lipid is …regulated by nuclear receptors. PPARα is not required for the biosynthesis, or induction upon cold exposure, but it is necessary for the elevated CoQ synthesis during peroxisomal induction. RXRα is involved in the basal synthesis of CoQ and also in the increased synthesis upon cold treatment but is not required for peroxisomal induction. Dietary CoQ in human appear in the blood and it is taken up by mononuclear but not polynuclear cells. The former cells display a specific phospholipid modification, an increase of arachidonic acid content. In monocytes the CoQ administration leads to a significant decrease of the β2-integrin CD11b and the complement receptor CD35. CD11b is one of the adhesion factors regulating the entry of these cells into the arterial wall which demonstrates that the anti-atherogenic effect of CoQ is mediated by other mechanisms beside its antioxidant protection. Show more

Keywords: Coenzyme Q metabolism, conjugation of metabolites, nuclear receptors, monocytes, β2-integrins, atherosclerosis

Citation: BioFactors, vol. 18, no. 1-4, pp. 11-22, 2003

Authors: Nohl, Hans | Staniek, Katrin | Kozlov, Andrey V. | Gille, Lars

Article Type: Research Article

Abstract: The chemistry of ubiquinone allows reversible addition of single electrons and protons. This unique property is used in nature for aerobic energy gain, for unilateral proton accumulation, for the generation of reactive oxygen species involved in physiological signaling and a variety of pathophysiological events. Since several years ubiquinone is also considered to play a major role in the control of lipid peroxidation, since this lipophilic biomolecule was recognized to recycle α-tocopherol radicals …back to the chain-breaking form, vitamin E. Ubiquinone is therefore a biomolecule which has increasingly focused the interest of many research groups due to its alternative pro- and antioxidant activity. We have intensively investigated the role of ubiquinone as prooxidant in mitochondria and will present experimental evidences on conditions required for this function, we will also show that lysosomal ubiquinone has a double function as proton translocator and radical source under certain metabolic conditions. Furthermore, we have addressed the antioxidant role of ubiquinone and found that the efficiency of this activity is widely dependent on the type of biomembrane where ubiquinone exerts its chain-breaking activity. Show more

Keywords: ubiquinone, reactive oxygen species, mitochondria, lysosomes, nitrite reductase

Citation: BioFactors, vol. 18, no. 1-4, pp. 23-31, 2003

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

Article Type: Research Article

Abstract: Our laboratories have described a novel class of ectoproteins at the cell surface with both NADH or hydroquinone oxidase (NOX) and protein disulfide-thiol interchange activities (ECTO-NOX proteins). The two activities exhibited by these proteins alternate to generate characteristic patterns of oscillations where the period length is independent of temperature. The period length for the constitutive ECTO-NOX is 24 min. Here we describe a distinctive age-related ECTO-NOX (arNOX) whose activity is blocked by coenzyme …Q_{10} . arNOX occurs exclusively in aged cells and tissues. The period length of the oscillations is 26 min. Rather than reducing 1/2 O_{2} to H_{2} O, electrons are transferred to O_{2} to form superoxide. Superoxide formation was demonstrated by superoxide dismutase-sensitive reduction of ferricytochrome c and by reduction of a superoxide-specific tetrazolium salt. Quinone inhibition was given by coenzymes Q_{8} , _{9} and Q_{10} but not by Q_{0} , Q_{2} , Q_{4} , Q_{6} or _{7} . The arNOX provides a mechanism to propagate reactive oxygen species generated at the cell surface to surrounding cells and circulating lipoproteins of importance to atherogenesis. Inhibition of arNOX by dietary coenzyme Q_{10} provides a rational basis for dietary coenzyme _{10} use to retard aging-related arterial lesions. Show more

Keywords: NADH (hydroquinone) oxidase, arNOX, coenzyme Q, aging, superoxide, atherogenesis

Citation: BioFactors, vol. 18, no. 1-4, pp. 33-43, 2003

Authors: Nordman, Tomas | Xia, Ling | Björkhem-Bergman, Linda | Damdimopoulos, Anastassios | Nalvarte, Ivan | Arnér, Elias S.J. | Spyrou, Giannis | Eriksson, Lennart C. | Björnstedt, Mikael | Olsson, Jerker M.

Article Type: Research Article

Abstract: Ubiquinol is a powerful antioxidant, which is oxidized in action and needs to be replaced or regenerated to be capable of a sustained effort. This article summarises current knowledge of extramitochondrial reduction of ubiquinone by three flavoenzymes, i.e. lipoamide dehydrogenase, glutathione reductase and thioredoxin reductase, belonging to the same pyridine nucleotide-disulfide oxidoreductase family. These three enzymes are the most efficient extramitochondrial ubiquinone reductases so far described. The reduction of ubiquinone by lipoamide …dehydrogenase and glutathione reductase is potently stimulated by zinc and the highest rate of reduction is achieved at acidic pH and the rates are equal with either NADPH or NADH as co-factors. The most efficient ubiquinone reductases are mammalian cytosolic thioredoxin reductases, which are selenoenzymes with a number of biological functions. Reduction of ubiquinone by thioredoxin reductase is in contrast to the other two enzymes investigated, inhibited by zinc and shows a sharp physiological pH optimum at pH 7.5. Furthermore, the reaction is selenium dependent as revealed from experiments using truncated and mutant forms of the enzyme and also in a cellular context by selenium treatment of transfected thioredoxin reductase overexpressing stable cell lines. The reduction of ubiquinone by the three enzymes offers a multifunctional system for extramitochondrial regeneration of an important antioxidant. Show more

Keywords: ubiquinone, lipoamide dehydrogenase, glutathione reductase, thioredoxin reductase, oxidative stress

Citation: BioFactors, vol. 18, no. 1-4, pp. 45-50, 2003

Authors: Brugè, F. | Tiano, L. | Cacciamani, T. | Principi, F. | Littarru, G.P.

Article Type: Research Article

Abstract: UV-C radiation is able to impair cellular functions by directly damaging DNA, and by inducing an increased formation of reactive oxygen species that leads to a condition of oxidative stress. In this study we evaluated different responses to UV insult of two leukemia cell lines, HL-60 and Raji, and the relationship with their CoQ_{10} content. DNA damage was monitored by means of the alkaline single cell gel electrophoresis (Comet assay); intracellular levels of ROS, …mitochondrial depolarization and cell viability was measured by flow cytometry. Raji cells appeared more resistant to the UV insult; moreover, they did not show any increase in ROS content and the extent of mitochondrial depolarisation was much lower than in HL 60 cell line. Raji cells also contained significantly higher levels of CoQ_{10} and their ability to incorporate and to reduce exogenous CoQ_{10} added to the culture medium was remarkably elevated compared with HL 60. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 51-63, 2003

Authors: Menke, T. | Gille, G. | Reber, F. | Janetzky, B. | Andler, W. | Funk, R.H.W. | Reichmann, H.

Article Type: Research Article

Abstract: Defects in mitochondrial energy metabolism due to respiratory chain disorders lead to a decrease in mitochondrial membrane potential (ΔΨ_{m} ) and induce apoptosis. Since coenzyme Q_{10} (CoQ_{10} ) plays a dual role as an antioxidant and bioenergetic agent in the respiratory chain, it has attracted increasing attention concerning the prevention of apoptosis in mitochondrial diseases. In this study the potential of CoQ_{10} to antagonize the apoptosis-inducing …effects of the respiratory chain inhibitor rotenone was explored by video-enhanced microscopy in SH-SY5Y neuroblastoma cells. The cationic fluorescent dye JC-1 which exhibits potential-dependent accumulation in mitochondria was used as an indicator to monitor changes in ΔΨ_{m} . The relative changes in fluorescence intensity after incubation with rotenone for 15 minutes were calculated. Pre-treatment with CoQ_{10} (10 or 100 μM) for 48h led to a significant reduction of rotenone-induced loss of ΔΨ_{m} . These results suggest, that cytoprotection by CoQ_{10} may be mediated by raising cellular resistance against the initiating steps of apoptosis, namely the decrease of ΔΨ_{m} . Whether these data may provide new directions for the development of neuroprotective strategies has to be investigated in future studies. Show more

Keywords: coenzyme Q_{10}, JC-1, mitochondrial membrane potential, apoptosis, SH-SY5Y

Citation: BioFactors, vol. 18, no. 1-4, pp. 65-72, 2003

Authors: Lochner, K. | Döring, O. | Böttger, M.

Article Type: Research Article

Abstract: The plant plasma membrane contains redox proteins able to mediate a trans-membrane electron flow. This electron flow might be responsible for the generation of the active oxygen species observed as a reaction to pathogen attack or stress. Vitamin K_{1} could be identified as a possible lipid soluble electron carrier in plant plasma membrane preparations. Such a function would be analogous to coenzyme Q in animal plasma membranes. What we are going to outline in …this contribution is a concept of how the electron transport system of the plant plasma membrane could interact with quinones, thus contributing to the metabolism of free radicals in plants. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 73-78, 2003

Authors: Mortensen, Svend Aage

Article Type: Research Article

Abstract: Energy starvation of the myocardium is probably a dominant feature of heart failure and attention has been directed towards agents which may stabilize myocardial metabolism and maintain adequate energy stores. A reduced myocardial tissue content of the essential redox-component and natural antioxidant Coenzyme Q_{10} (CoQ_{10} ) has been detected in patients with heart failure and the observed level of CoQ_{10} deficiency was correlated to the severity of heart …failure. CoQ_{10} fulfills various criteria of an obvious adjunct in patients with symptomatic heart failure: it is devoid of significant side effects and it improves symptoms and quality of life. Till this date, several double-blind placebo-controlled trials with CoQ_{10} supplementation in more than 1000 patients have been positive and statistically significant with respect to various clinical parameters, e.g. improvement in NYHA Class, exercise capacity and reduced hospitalisation frequency. Also treatment with CoQ_{10} led to a significant improvement of relevant hemodynamic parameters. In only 3 out of 13 double-blind studies comprising 10% of the total number of patients treated the results were neutral. Thus, based on the available controlled data CoQ_{10} is a promising, effective and safe approach in chronic heart failure. This is why a double-blind multicenter trial with focus on morbidity and mortality has been planned to start in 2003: Q-SYMBIO. Patients in NYHA classes III to IV (N=550) receiving standard therapy are being randomized to treatment with CoQ_{10} 100 mg t.i.d. or placebo in parallel groups. End-points in a short-term evaluation phase of 3 months include symptoms, functional capacity and biomarker status (BNP). The aim of a subsequent 2-year follow-up study is to test the hypothesis that CoQ_{10} may reduce cardiovascular morbidity (unplanned cardiovascular hospitalisation due to worsening heart failure) and mortality as a composite endpoint. This trial should help to establish the future role of CoQ_{10} as part of a maintenance therapy in patients with chronic heart failure. Show more

Keywords: coenzyme Q_{10}, heart failure, clinical trials, efficacy, safety

Citation: BioFactors, vol. 18, no. 1-4, pp. 79-89, 2003

Authors: Rosenfeldt, Franklin | Hilton, Deborah | Pepe, Salvatore | Krum, Henry

Article Type: Research Article

Abstract: Coenzyme Q_{10} in physical exercise. We identified eleven studies in which CoQ_{10} was tested for an effect on exercise capacity, six showed a modest improvement in exercise capacity with CoQ_{10} supplementation but five showed no effect. CoQ_{10} in hypertension. We identified eight published trials of CoQ_{10} in hypertension. Altogether in the eight studies the mean decrease in systolic blood pressure was 16 mm Hg and …in diastolic blood pressure, 10 mm Hg. Being devoid of significant side effects CoQ_{10} may have a role as an adjunct or alternative to conventional agents in the treatment of hypertension. CoQ_{10} in heart failure. We performed a randomised double blind placebo-controlled pilot trial of CoQ_{10} therapy in 35 patients with heart failure. Over 3 months, in the CoQ_{10} patients but not in the placebo patients there were significant improvements in symptom class and a trend towards improvements in exercise time. Meta-analysis of randomised trials of coenzyme Q_{10} in heart failure. In nine randomised trials of CoQ_{10} in heart failure published up to 2003 there were non-significant trends towards increased ejection fraction and reduced mortality. There were insufficient numbers of patients for meaningful results. To make more definitive conclusions regarding the effect of CoQ_{10} in cardiac failure we recommend a prospective, randomised trial with 200–300 patients per study group. Further trials of CoQ_{10} in physical exercise and in hypertension are recommended. Show more

Keywords: coenzyme Q_{10}, exercise, hypertension, heart failure

Citation: BioFactors, vol. 18, no. 1-4, pp. 91-100, 2003

Authors: Langsjoen, Peter H. | Langsjoen, Alena M.

Article Type: Research Article

Abstract: The depletion of the essential nutrient CoQ_{10} by the increasingly popular cholesterol lowering drugs, HMG CoA reductase inhibitors (statins), has grown from a level of concern to one of alarm. With ever higher statin potencies and dosages, and with a steadily shrinking target LDL cholesterol, the prevalence and severity of CoQ_{10} deficiency is increasing noticeably. An estimated 36 million Americans are now candidates for statin drug therapy. Statin-induced CoQ_{10} …depletion is well documented in animal and human studies with detrimental cardiac consequences in both animal models and human trials. This drug-induced nutrient deficiency is dose related and more notable in settings of pre-existing CoQ_{10} deficiency such as in the elderly and in heart failure. Statin-induced CoQ_{10} deficiency is completely preventable with supplemental CoQ_{10} with no adverse impact on the cholesterol lowering or anti-inflammatory properties of the statin drugs. We are currently in the midst of a congestive heart failure epidemic in the United States, the cause or causes of which are unclear. As physicians, it is our duty to be absolutely certain that we are not inadvertently doing harm to our patients by creating a wide-spread deficiency of a nutrient critically important for normal heart function. Show more

Keywords: coenzyme Q_{10} deficiency, ubiquinone, CoQ_{10}, HMG CoA reductase inhibitors, statins, congestive heart failure, CHF

Citation: BioFactors, vol. 18, no. 1-4, pp. 101-111, 2003

Authors: Passi, Siro | Stancato, Andrea | Aleo, Enrico | Dmitrieva, Anna | Littarru, Gian Paolo

Article Type: Research Article

Abstract: It has been shown that treating hypercholesterolemic patients (HPC) with statins leads to a decrease, at least in plasma, not only in cholesterol, but also in important non-sterol compounds such as ubiquinone (CoQ_{10} ), and possibly dolichols, that derive from the same biosynthetic pathway. Plasma CoQ_{10} decrease might result in impaired antioxidant protection, therefore leading to oxidative stress. In the present paper we investigated the levels in plasma, lymphocytes …and erythrocytes, of ubiquinol and ubiquinone, other enzymatic and non-enzymatic lipophilic and hydrophilic antioxidants, polyunsaturated fatty acids of phosfolipids and cholesterol ester fractions, as well as unsaturated lipid and protein oxidation in 42 hypercholesterolemic patients treated for 3 months. The patients were treated with different doses of 3 different statins, i.e. atorvastatin 10 mg (n = 10) and 20 mg (n = 7), simvastatin, 10 mg (n = 5) and 20 mg (n = 10), and pravastatin, 20 mg (n = 5) and 40 mg (n = 5). Simvastatin, atorvastatin and pravastatin produced a dose dependent plasma depletion of total cholesterol (t-CH), LDL-C, CoQ_{10} H_{2} , and CoQ_{10} , without affecting the CoQ_{10} H_{2} /CoQ_{10} ratio. The other lipophilic antioxidants (d-RRR-α-tocopherol-vit E-, γ-tocopherol, vit A, lycopene, and β-carotene), hydrophilic antioxidants (vit C and uric acid), as well as, TBA-RS and protein carbonyls were also unaffected. Similarly the erythrocyte concentrations of GSH and PUFA, and the activities of enzymatic antioxidants (Cu,Zn-SOD, GPx, and CAT) were not significantly different from those of the patients before therapy. In lymphocytes the reduction concerned CoQ_{10} H_{2} , CoQ_{10} , and vit E; other parameters were not investigated. The observed decline of the levels of CoQ_{10} H_{2} and CoQ_{10} in plasma and of CoQ_{10} H_{2} , CoQ_{10} and vit E in lymphocytes following a 3 month statin therapy might lead to a reduced antioxidant capacity of LDL and lymphocytes, and probably of tissues such as liver, that have an elevated HMG-CoA reductase enzymatic activity. However, this reduction did not appear to induce a significant oxidative stress in blood, since the levels of the other antioxidants, the pattern of PUFA as well as the oxidative damage to PUFA and proteins resulted unchanged. The concomitant administration of ubiquinone with statins, leading to its increase in plasma, lymphocytes and liver may cooperate in counteracting the adverse effects of statins, as already pointed out by various authors on the basis of human and animal studies. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 113-124, 2003

Authors: Silver, Marc A. | Langsjoen, Peter H. | Szabo, Szabolcs | Patil, Harish | Zelinger, Allan

Article Type: Research Article

Abstract: Lipid-lowering statins are thought to have a favorable safety profile. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting step of mevalonate synthesis. Mevalonate is the substrate for further synthesis of cholesterol and Co Enzyme Q_{10} (CoQ_{10} ). CoQ_{10} plays an important role during oxidative phosphorylation in the myocardial cell. Since myocardial diastolic function is a highly ATP dependent, we reasoned that early changes of diastolic function …may be an early marker of ventricular dysfunction Methods: Patients who are to commence on statin therapy will be enrolled in the trial. Baseline measurements of plasma CoQ_{10} , total cholesterol, LDL, HDL, CoQ_{10} /LDL ratio, peak E, peak A velocities, E/A ratio, deceleration time, isovolumetric relaxation time, color M-mode propagation velocity will be performed and patients will then begin to take Oral atorvastatin (Lipitor, Parke-Davis) 20 mg daily for three to six months. All baseline measurement will be repeated after 3 to 6 months of statin therapy. Those patients demonstrating > 1 measurement of diastolic LV function that worsened during the 3 to 6 months of statin therapy will be supplemented with CoQ_{10} 300 mg. daily for 3 months. A followup echocardiogram and blood CoQ_{10} level will be measured in patients who received CoQ_{10} supplementation. Results: Statistical analysis will be performed using the paired t test to compare coenzyme levels and echocardiographic indices at baseline and after treatment and after supplementation. Show more

Keywords: statin, Co-Enzyme Q_{10}, diastolic dysfunction

Citation: BioFactors, vol. 18, no. 1-4, pp. 125-127, 2003

Authors: Hodgson, Jonathan M. | Watts, Gerald F.

Article Type: Research Article

Abstract: Coenzyme Q_{10} (CoQ) is an endogenously synthesised compound that acts as an electron carrier in the mitochondrial electron transport chain. The presence of adequate tissue concentrations of CoQ may be important in limiting oxidative and nitrosative damage in vivo. Oxidative and nitrosative stress are likely to be elevated in conditions such as diabetes and hypertension. In these conditions elevated oxidative and nitrosative stress within the arterial wall may contribute to increased blood …pressure and vascular dysfunction. The major focus of this review is the potential of CoQ to improve vascular function and lower blood pressure. Although there is substantial indirect support for the putative mechanism of effect of CoQ on the vascular system, to date there is little direct support for an effect of CoQ on in vivo markers of oxidative or nitrosative stress. The limited data available from studies in animal models and from human intervention studies are generally consistent with a benefit of CoQ on vascular function and blood pressure. The observed effects of CoQ on these endpoints are potentially important therapeutically. However, before any firm clinical recommendations can be made about CoQ supplementation, further intervention studies in humans are needed to investigate the effects of CoQ on vascular function, blood pressure and cardiovascular outcomes. The particularly relevant groups of patients for these studies are those with insulin resistance, type 2 diabetes, hypertension and the metabolic syndrome. Show more

Keywords: coenzyme Q_{10}, vascular function, endothelial function, blood pressure, oxidative stress, nitrosative stress

Citation: BioFactors, vol. 18, no. 1-4, pp. 129-136, 2003

Authors: Bindu, R. | Venkataraman, B.V. | Rao, Aparna V.S. | Ramasarma, T.

Article Type: Research Article

Abstract: Treatment of coenzyme Q with ozone yielded a degradation product having unmodified ring that retained its spectral characteristics and a truncated side-chain that made it water-soluble. This derivative, but not the intact lipid-quinone, showed relaxation of phenylephrine-contracted rat arterial rings. This effect offers an explanation for the known hypotensive action of exogenous coenzyme Q regardless of its side-chain length.

Keywords: coenzyme Q, ubiquinone, relaxation of arterial rings, water-soluble degradation product, BP lowering effect

Citation: BioFactors, vol. 18, no. 1-4, pp. 137-143, 2003

Authors: Naini, Ali | Lewis, Vernice-Jackson | Hirano, Michio | DiMauro, Salvatore

Article Type: Research Article

Abstract: Our findings in 19 new patients with cerebellar ataxia establish the existence of an ataxic syndrome due to primary CoQ_{10} deficiency and responsive to CoQ_{10} therapy. As all patients presented cerebellar ataxia and cerebellar atrophy, this suggests a selective vulnerability of the cerebellum to CoQ_{10} deficiency. We investigated the regional distribution of coenzyme Q_{10} in the brain of adult rats and in the brain of one …human subject. We also evaluated the levels of coenzyme Q_{9} (CoQ_{9} ) and CoQ_{10} in different brain regions and in visceral tissues of rats before and after oral administration of CoQ_{10} . Our results show that in rats, amongst the seven brain regions studied, cerebellum contains the lowest level of CoQ. However, the relative proportion of CoQ_{10} was the same (about 30% of total CoQ) in all regions studied. The level of CoQ_{10} is much higher in brain than in blood or visceral tissue, such as liver, heart, or kidney. Daily oral administration of CoQ_{10} led to substantial increases of CoQ_{10} concentrations only in blood and liver. Of the four regions of one human brain studied, cerebellum again had the lowest CoQ_{10} y concentration. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 145-152, 2003

Authors: Beal, M. Flint | Shults, Clifford W.

Article Type: Research Article

Citation: BioFactors, vol. 18, no. 1-4, pp. 153-161, 2003

Authors: Cooper, J.M. | Schapira, A.H.V.

Article Type: Research Article

Abstract: Mitochondria clearly play a central role in the pathogenesis of Friedreich's Ataxia. The most common genetic abnormality results in the deficiency of the protein frataxin, which is targeted to the mitochondrion. Research since this discovery has indicated that mitochondrial respiratory chain dysfunction, mitochondrial iron accumulation and oxidative damage are important components of the disease mechanism. While the role of frataxin is not known, evidence is currently pointing to a role in either mitochondrial …iron handling or iron sulphur centre synthesis. These advances in our understanding of the disease mechanisms are enabling therapeutic avenues to be explored, in particular the use of established drugs such as antioxidants and enhancers of respiratory chain function. Vitamin E therapy has been shown to be beneficial in patients with ataxia with vitamin E deficiency, and CoQ_{10} therapy was effective in some patients with ataxia associated with CoQ_{10} deficiency. A combined therapy involving long term treatment with high doses of vitamin E and coenzyme Q_{10} has jointly targeted two of the major features of Friedreich's Ataxia; decreased mitochondrial respiratory chain function and increased oxidative stress. This therapy clearly showed a rapid and sustained increase in the energy generated by the FRDA heart muscle, nearly returning to normal levels. The improvements in skeletal muscle energy generation parallel those of the heart but to a lower level. While this therapy appeared to slow the predicted progression of some clinical symptoms a larger placebo controlled study is required to confirm these observations. Other antioxidant strategies have involved the use of Idebenone, selenium and N acetyl cysteine but only the use of Idebenone has involved structured trials with relatively large patient numbers. Idebenone clearly had an impact upon the cardiac hypertrophy in the majority of patients, although there have not been any other significant benefits reported to date. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 163-171, 2003

Authors: Sikorska, Marianna | Borowy-Borowski, Henryk | Zurakowski, Bogdan | Walker, P. Roy

Article Type: Research Article

Abstract: We have derivatised α-tocopherol (vitamin E) to a water-soluble polyoxyethanyl-α – tocopheryl sebacate (PTS) and discovered that it formed a non-covalent complex with CoQ_{10} at a molar ratio of 2:1 (PTS-CoQ_{10} ). This complex was water-soluble and remained stable for extended periods of time. After oral delivery of the formulation into rats PTS was hydrolysed to vitamin E and elevated levels of both vitamin E and CoQ_{10} …in blood plasma were detected within 1 h. Thus, this aqueous formulation contains a combination of two potent antioxidants. The formulation's efficacy was tested against ischemic brain damage caused by a transient (8~min) bilateral occlusion of the common carotid arteries in rats. The animals received PTS-CoQ_{10} by two intraperitoneal injections given immediately after ischemia and 3~h later and the brain damage was assessed up to 12 days post-ischemia. A significant neuroprotection was observed in the CA1 hippocampal region, for example at 12 days approximately 50% of CA1 neurons were still alive in the treated animals versus less than 5% in the non-treated group. Our data is consistent with previously published observations indicating the therapeutic potential of antioxidants for treatments of ischemia/reperfusion injuries and the formulation described here is particularly appropriate for the application in acute conditions, such as stroke or cardiac arrest. Show more

Keywords: neuroprotection, coenzyme Q_{10}, vitamin E, antioxidants, ischemia, reperfusion

Citation: BioFactors, vol. 18, no. 1-4, pp. 173-183, 2003

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

Authors: Battino, M. | Bompadre, S. | Leone, L. | Devecchi, E. | Degiuli, A. | D'Agostino, F. | Cambiè, G. | D'Agostino, M. | Faggi, L. | Colturani, G. | Gorini, A. | Villa, R.F.

Article Type: Research Article

Abstract: Neurodegenerative Diseases represent the most commmon cause of Dementia, about 5–10% of the population aged above 65 years and about 30% above 80 years. A study about Apo-E alleles, Coenzyme Q and Vitamins E as biological indicators was performed in plasma samples of patients aged from 30 to 85 years, affected by Neurodegenerative Diseases. The results were compared with control subjects of approximately the same ages as the reference group. A frequency of 21.7% …of ε4 allele in control group was estimated, against 15.8% observed in patients. The frequency of ε2 and ε3 alleles was 13.0% and 65.2% in the control group against 10.5% and 73.7% in patients. No significant differences were observed between the frequency of ε3/ε3 genotype and ε3/ε4 genotype in the control group compared to patients' group. The frequencies observed in ε2/ε3 genotype groups were 8.7% vs 15.8% and of e2/e4 genotype 17.4% vs 5.3%. The ε2/ε2 and ε4/ε4 genotypes were not identified in any groups. Plasma CoQ_{10} concentrations were similar in patient and control groups and no differences were found even taking into account the distribution of male and female subjects in the two groups. Also, vitamin E did not provide evidence of any differences between groups and the analysis among sexes revealed that again vitamin E concentrations were similar in between subgroups. Show more

Keywords: coenzyme Q, Vitamin E, Alzheimer, ApoE

Citation: BioFactors, vol. 18, no. 1-4, pp. 277-281, 2003

Authors: Sinatra, Drew S. | Sinatra, Stephen T. | Heyser, Charles J.

Article Type: Research Article

Abstract: To explore the possibility that Coenzyme Q_{10} (CoQ_{10} ) supplementation stabilizes psychomotor behavioral function in the aging organism, the behavioral effects of CoQ_{10} were evaluated in young adult male C57BL/6 mice (3 months of age) and aged C57BL/6 mice (24 months of age). Mice treated with CoQ_{10} exhibited significantly greater locomotor activity as reflected by an increase in square crosses than non-drug controls. The administration …of CoQ_{10} increased all aspects of exploratory behavior in the open field. The effect was uniform across all mice and did not interact with age. Younger animals and aged animals treated with CoQ_{10} may adapt rapidly to novel areas, or they are less fearful of exploration. The behavioral activation observed in CoQ_{10} treated mice may be the result of increased locomotor activity, psychomotor stimulation, or decreased anxiety. Show more

Keywords: mice, CoEnzyme Q_{10}, psychomotor stimulation, exploratory behavior, anxiety

Citation: BioFactors, vol. 18, no. 1-4, pp. 283-287, 2003

Authors: Passi, Siro | De Pità, Ornella | Grandinetti, Mauro | Simotti, Cristina | Littarru, Gian Paolo

Article Type: Research Article

Abstract: The concentration of Vitamin E (vit E) and ubiquinone (CoQ_{10} ), which together with squalene (SQ), play a key role against external oxidative insult, has been shown to decrease significantly during ageing. The aim of the present study is to inquire the effect of the combined use of topical bio-cosmetics containing natural active principles (including sebum-like lipid fractions, sebum and epidermal lipophilic and hydrophilic antioxidants), and oral antioxidant supplements on the …antioxidant content of sebum and stratum corneum. We therefore treated the face and the back of 50 female volunteers aged 21–40, daily for two months, with a base cream containing 0.05% ubiquinone, 0.1% vit E, and 1% squalene. In addition 50 mg of CoQ_{10} + 50 mg of d-RRR-α-tocopheryl acetate + 50 μg of selenium were administered orally to half of the volunteers (Group A). Group B was represented by 25 volunteers who were treated only topically. Every 15 days during treatment the levels of CoQ_{10} , vit E and SQ were verified in sebum, stratum corneum, and plasma. The daily topical application of the cream led to a significant increase, that peaked after 60 days, of the levels of CoQ_{10} , d-RRR-α-tocopherol and SQ in the sebum (Group B), without significantly affecting the stratum corneum or plasma concentrations of the redox couple CoQ_{10} H_{2} /CoQ_{10} and vit E. The concomitant oral admistration of antioxidants produced in Group A a significant increase of the levels of CoQ_{10} H_{2} /CoQ_{10} and vit E both in plasma and stratum corneum after 15 and 30 days treatment respectively, compared to Group B. However the sebum levels of lipophilic antioxidants and SQ did not show a significant increase. After the treatments, the levels of CoQ_{10} H_{2} /CoQ_{10} , vit E and SQ went back to basal levels within 6–8 days in sebum, 12–16 days in the stratum corneum, and 3–6 days in plasma. Therefore topical application of the antioxidants was able to increase their level in sebum, while the concomitant oral administration also affected the levels of vit E and CoQ_{10} in the stratum corneum. Show more

Citation: BioFactors, vol. 18, no. 1-4, pp. 289-297, 2003

Authors: Battino, M. | Giunta, S. | Galeazzi, L. | Galeazzi, R. | Mosca, F. | Santolini, C. | Principi, F. | Ferretti, G. | Bacchetti, T. | Bencivenga, R. | Piani, M. | Riganello, G. | Littarru, G.P.

Article Type: Research Article

Abstract: The aim of this study was to inquire the antioxidant status in plasma and lipoproteins isolated from normal subjects possessing different ApoE genotypes. For this purpose we investigated blood samples from 106 healthy blood donors: the distribution of ApoE alleles (E2/E2 = 0.9%, E2/E3 = 10.4%, E2/E4 = 2.8%, E3/E3 = 71.7%, E3/E4 = 12.3% and E4/E4 1.9% with 1, 11, 3, 76, 13, and 2 subjects respectively for each genotype) was in agreement with previous …data. Almost no differences were found in the concentrations of both coenzyme Q_{10} (CoQ_{10} ) and vitamin E for the different genotypes. Concentration of CoQ_{10} in isolated lipoproteins was also similar, in the different genotypes, when referred to cholesterol; CoQ_{10} in LDL was higher for the E3/E3 subjects when referred to protein. Neither CoQ_{10} nor vitamin E correlated with paraoxonase (PON) activity or cholesteryl-ester hydroperoxides (CHP). Furthermore, there was no correlation between the same lipophilic antioxidants and CHP levels. The only E2 homozygous subject found had high levels of PON and low levels of CHP; the two E4/E4 subjects had low PON activity together with low levels of CHP. Show more

Keywords: Vitamin E, LDL, HDL, paraoxonase, cholesteryl-esters hydroperoxide

Citation: BioFactors, vol. 18, no. 1-4, pp. 299-305, 2003

Authors: Sun, I.L. | Sun, L.E. | Sun, E.E. | Crane, F.L. | Willis, R.

Article Type: Research Article

Abstract: This study was organized by Professor Karl Folkers with the objective of finding derivatives of coenzyme Q which could be more effectively absorbed and would give better biomedical effects. In this series all the compounds are 2,3 dimethoxy, 5 methyl p benzoquinone with modified side chains in the 6 position. The modifications are primarily changes in chain length, unsaturation, methyl groups and addition of terminal phenyl groups. The test system evaluates the growth of serum deficient …HL60, 3T3 and HeLa cells in the presence of coenzyme Q_{10} or coenzyme Q analogs. Short chain coenzyme Q homologues such as coenzyme Q_2 give poor growth but compounds with saturated short aliphatic side chains from C10 to C18 produce good growth. Introduction of a single double bond at the 2' or 8' position in the aliphatic chain retains growth stimulation at low concentration but introduces inhibition at higher concentration. Introduction of a 3' methyl group in addition to the 2' enyl site in the side chain decreases the growth response and maintains inhibition. Addition of a terminal phenyl group to the side chain from C5 to C10 can produce analogs which give strong stimulation or strong inhibition of growth. The action of the analogs is in addition to the natural coenzyme Q in the cell and is not based on restoration of activity after depletion of normal coenzyme Q. The effects may be based on any of the sites in the cell where coenzyme Q functions. For example, coenzyme Q_2 is known to decrease mitochondrial membrane potential whereas the analog with a 10C aliphatic side chain increases potential. Both of these compounds stimulate plasma membrane electron transport. Inhibition of apoptosis by coenzyme Q may also increase net cell proliferation and the 10C analog inhibits the permeability transition pore. Show more

Keywords: coenzyme Q analogs, cell growth

Citation: BioFactors, vol. 18, no. 1-4, pp. 307-314, 2003

Article Type: Other

Citation: BioFactors, vol. 18, no. 1-4, pp. 315-315, 2003