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Elevated levels of oxidative nucleic acid modifications have been proposed to be associated with some of the clinical characteristics of Down syndrome. Oral intake of coenzyme Q10 improves oxidative status and shows a tendency toward protective effect on DNA oxidation in certain age groups of children with Down syndrome. Here, we demonstrate that long-term (i.e., 4 years) treatment with coenzyme Q10 (ubiquinone) at the dosage of 4 mg/kg/d does not affect whole body DNA and RNA oxidation.

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INTRODUCTION: The male sperm counts decline due to environmental factors, such as pesticides, heavy metals and exogenous estrogens causing negative impact on spermatogenesis. The low testosterone levels are associated with lower levels of antioxidants that protect against free radical damage to glands that produce testosterone. The earlier studies showed that the supplementation of vitamins and antioxidants including 10mg Ubiquinol per-day increases in sperm count and motility. MATERIALS AND METHODS: The Ubiquinol is strong antioxidant, hence in view of the above study 150 mg/day Ubiquinol was supplemented to 60 men with age group of 20-40 years. The patients were supplemented for six months, the testosterone level and sperm parameters were analysed before and after supplementation of Ubiquinol every month up to six months. The total sperm count increased by 53% (p<0.05). RESULTS: The total sperm motility was observed 26% (p<0.05) high after supplementations. Out of total motility, the quantity of rapidly motile sperm increased 41% (p<0.05). The number of sluggish motile sperm was decreased approximate 29% (p<0.05). The non motile sperm count was also decreased up to 55% (p<0.05). CONCLUSION: The testosterone level is maintained during the study and morphology of flagella of sperm has improved. The finding suggests that the supplementation of Ubiquinol may be beneficial for oligospermic patients.

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Reactive oxygen species not only cause damage but also have a physiological role in the protection against pathogens and in cell signalling. Mitochondrial nutrients, such as coenzyme Q10 and α-lipoic acid, beside their acknowledged antioxidant activities, show interesting features in relation to their redox state and consequent biological activity. In this study, we tested whether oral supplementation with 200 mg/day of coenzyme Q10 alone or in association with 200 mg/die of α-lipoic acid for 15 days on 16 healthy subjects was able to modulate the oxidative status into different compartments (plasma and cells), in basal condition and following an oxidative insult in peripheral blood lymphocytes exposed in vitro to H2O2. Data have shown that tested compounds produced antioxidant and bioenergetic effects improving oxidative status of the lipid compartment and mitochondrial functionality in peripheral blood lymphocytes. Simultaneously, an increased intracellular reactive oxygen species level was observed, although they did not lead to enhanced DNA oxidative damage. Coenzyme Q10 and α-lipoic acid produced beneficial effects also steering intracellular redox poise toward a pro-oxidant environment. In contrast with other antioxidant molecules, pro-oxidant activities of tested mitochondrial nutrients and consequent oxidant mediated signalling, could have important implications in promoting adaptive response to oxidative stress.

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Coenzyme Q10 (CoQ10 or ubiquinone) is an essential component of the mitochondrial electron transport chain and is also present in various cellular membranes and in plasma lipoproteins. Diabetes, cardiovascular, neurodegenerative, and preeclampsia diseases are all associated with an alteration of CoQ10 level or its redox status. During pregnancy, we note that the plasma content of CoQ10 is significantly higher than amniotic. In the fetal growth restriction group, amniotic total CoQ10 levels were significantly higher versus healthy, while the amniotic oxygen radical absorbing capacity level was significantly lower. A significant negative correlation was observed between amniotic total CoQ10 and birthweight. Our observation leads to the hypothesis that the amniotic midtrimester CoQ10 content may be a marker of subsequent obstetric complications.

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Nanostructured lipid carriers (NLC) represent an emerging tool for drug delivery and are characterized by important features which promote increased bioavailability and epithelial penetration of lipophilic compounds. However, despite these advantages, their potential cytotoxicity should not be underestimated, especially under in vivo usage conditions. Here we analyzed the viability, intracellular reactive oxygen species (ROS), oxidative DNA damage and mitochondrial functionality in human dermal fibroblasts (HDF) in the presence of NLC either empty or loaded with the reduced or oxidized form of Coenzyme Q10. Experiments were carried out under standard culture conditions and under oxidative stress induced by UVA irradiation, where the latter treatment significantly affected all the endpoints tested above compared to the non-UVA condition. The data show that NLC alone, whether exposed or not exposed to UVA, produce a slight, though significant decrease in cell viability associated with enhanced oxidative stress, which did not however lead to oxidative DNA damage nor mitochondrial impairment. Reduced CoQ10-NLC, differently from oxidized CoQ10-NLC, were able to efficiently counteract UVA-associated mitochondrial depolarization suggesting a potential role of this molecule in antiageing cosmetological formulations. In conclusion, our results suggest that interactions of NLC with cells and biomolecules should be routinely assessed for understanding their compatibility and toxicity, not only under normal conditions, but also under any chemical or physical stress which these delivery systems might be subjected to during their employment.

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Clinical evidence demonstrates that ubiquinol-10, the reduced active form of coenzyme Q10 (CoQ10H2), improves endothelial function through its antioxidant and probably its anti-inflammatory properties. We previously reported that a biomarker combination including miR-146a, its target protein IL-1 receptor-associated kinase (IRAK-1), and released interleukin (IL)-6, here collectively designated as MIRAKIL, indicates senescence-associated secretory phenotype (SASP) acquisition by primary human umbilical vein endothelial cells (HUVECs). We explore the ability of short- and long-term CoQ10H2 supplementation to affect MIRAKIL in HUVECs, used as a model of vascular aging, during replicative senescence in the absence/presence of lipopolysaccharide (LPS), a proinflammatory stimulus. Senescent HUVECs had the same ability as young cells to internalize CoQ10 and exhibit an improved oxidative status. LPS-induced NF-κB activation diminished after CoQ10H2 pretreatment in both young and senescent cells. However, short-term CoQ10H2 supplementation attenuated LPS-induced MIRAKIL changes in young cells; in senescent cells CoQ10H2 supplementation significantly attenuated LPS-induced miR-146a and IRAK-1 modulation but failed to curb IL-6 release. Similar results were obtained with long-term CoQ10H2 incubation. These findings provide new insights into the molecular mechanisms by which CoQ10H2 stems endothelial cell inflammatory responses and delays SASP acquisition. These phenomena may play a role in preventing the endothelial dysfunction associated with major age-related diseases.

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The objective of this study was to evaluate the possible benefits of coenzyme Q10 and selenium supplementation administered to patients with statin-associated myopathy (SAM). Sixty eligible patients entered the pilot study. Laboratory examination (CoQ10, selenium, creatin kinase) and intensity of SAM (visual scale) were performed at baseline, after 1 month, and at the end of study at month 3. Plasma levels of CoQ10 increased from 0.81 ± 0.39 to 3.31 ± 1.72 µmol/L in the active group of patients treated by CoQ10, compared with the placebo (p = 0.001). Also, the symptoms of SAM significantly improved in the active group (p < 0.001): the intensity of muscle pain decreased from 6.7 ± 1.72 to 3.2 ± 2.1 (p < 0.01, -53.4 ± 28.2%); muscle weakness decreased from 7.0 ± 1.63 to 2.8 ± 2.34 (p < 0.01, -60 ± 24.0%); muscle cramps decreased from 5.33 ± 2.06 to 1.86 ± 2.42, p < 0.01, -65 ± 28%); tiredness decreased from the initial 6.7 ± 1.34 to 1.2 ± 1.32 (p < 0.01, -82 ± 22%). We did not observe any significant changes in the placebo group. In conclusion, supplementation of statin-treated patients with CoQ10 resulted in a decrease in the symptoms of SAM, both in absolute numbers and intensity. Additional selenium supplementation was not associated with any statistically significant decrease of SAM. However, it is not possible to draw any definite conclusions, even though this study was carried out in double-blind fashion, because it involved a small number of patients.

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Human NAD(P)H: quinone oxidoreductase 1 (NQO1) catalyzes the obligatory two-electron reduction of quinones. For this peculiar catalytic mechanism, the enzyme is considered an important cytoprotector. The NQO1 gene is expressed in all human tissues, unless a polymorphism due to C609T point mutation is present. This polymorphism produces a null phenotype in the homozygous condition and reduced enzyme activity in the heterozygous one. We previously demonstrated that two cell lines of haematopoietic origin, HL60 and Raji cells, possess the same heterozygous genotype, but different phenotypes; as expected for a heterozygous condition the HL60 cell line showed a low level of enzyme activity, while the Raji cell line appeared as null phenotype. The level of NQO1 mRNA was similar in the two cell lines and the different phenotype was not due to additional mutations or to expression of alternative splicing products. Here we show that in Raji BL cell line with heterozygous genotype the null NQO1 phenotype is due to 20S proteasome degradation of wild type and mutant protein isoforms and is not directly linked to C609T polymorphism. This finding may have important implications in B-cell differentiation, in leukaemia risk evaluation and in chemotherapy based on proteasome inhibitors.

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Olive oil consumption is associated with protective cardiovascular properties, including some beneficial modifications in lipoprotein profile and composition. Coenzyme Q(10) (CoQ(10)) exerts a protective effect on plasma lipoproteins. Aim of the study was to investigate whether extra virgin (EV) olive oil enriched with CoQ(10) affects CoQ(10) levels and oxidative status in plasma and in isolated lipoproteins. Twelve subjects were administered 20 mL olive oil per day for 2 weeks, followed by 2 weeks of olive oil enriched with 20 mg and 2 more weeks with 40 mg of CoQ(10). Plasma and isolated lipoproteins were collected in each phase of the study and subsequently analyzed to assess lipid profile, CoQ10 levels, ORAC assay, resistance of lipoproteins to peroxidation and paroxonase 1 activity. Plasma CoQ(10) levels significantly increased with the 20 mg (+73%) and 40 mg dose (+170%), while the percentage of oxidized CoQ(10) decreased. A significant inverse correlation was found in plasma between percentage of oxidized CoQ(10) and total antioxidant capacity. A lower susceptibility of LDL to peroxidation was also found. Finally, a positive correlation was observed between concentration of CoQ(10) in HDL and paraoxonase-1 activity. EV olive oil enriched with both doses of CoQ(10) significantly affects its bioavailability and plasma redox status. These changes are associated with a decreased susceptibility of plasma lipoproteins to peroxidation associated with a chain-breaking antioxidant activity of the formulation.

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Oxidative stress is known to play a relevant role in Down syndrome (DS) and its effects are documented from embryonic life. Oxidative DNA damage has been shown to be significantly elevated in Down syndrome patients, and this has been indicated as an early event promoting neurodegeneration and Alzheimer type dementia. The aim of this study was to investigate the efficacy of coenzyme Q(10) (CoQ(10)) in delaying the effect of oxidative damage in these patients. In our previous study we demonstrated a mild protective effect of CoQ(10) on DNA, although the treatment was unable to modify the overall extent of oxidative damage at the patient level. Possible limitations of the previous study were: time of treatment (6 months) or spectrum of DNA lesions detected. In order to overcome these limitations we planned a continuation of the trial aimed at evaluating the effects of CoQ(10) following a prolonged treatment. Our results highlight an age-specific reduction in the percentage of cells showing the highest amount of oxidized bases, indicating a potential role of CoQ(10) in modulating DNA repair mechanisms.

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Oxidative stress is a mechanism underlying different kinds of infertility in human males. However, different results can be observed in relation to the method used for its evaluation. Varicocele patients show a number of biochemical abnormalities, including an altered distribution of coenzyme Q between seminal plasma and sperm cells and also an apparent defect in the utilization of antioxidants. Moreover, an influence of systemic hormones on seminal antioxidant system was observed too. Finally, the effects of surgical treatment on oxidativestress indexes and the possible usefulness of some medical therapies, like coenzyme Q supplementation, are discussed. In conclusion, published data show a role of oxidative stress in varicocele-related male infertility, but at present we do not know the precise molecular mechanisms underlying these phenomena.

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Coenzyme Q(10) (CoQ(10) ) is a key component of the mitochondrial respiratory chain and, therefore, is essential for the bioenergetics of oxidative phosphorylation. It is also endowed with antioxidant properties, and recent studies pointed out its capability of affecting the expression of different genes. In this review, we analyze the data on the mechanisms by which CoQ(10) interacts with skin aging processes. The effect of CoQ(10) in preserving mitochondrial function cooperates in maintaining a proper energy level, which serves to prevent the aging skin from switching to anaerobic energy production mechanisms. Furthermore, the antioxidant capacity of CoQ(10) contributes to a positive effect against UV-mediated oxidative stress. Some of these effects have been assessed also in vivo, by the sensitive technique of ultraweak photoemission. Finally, CoQ(10) has been shown to influence, through a gene induction mechanism, the synthesis of some key proteins of the skin and to decrease the expression of some metalloproteinase such as collagenase. These mechanisms may also contribute to preserve collagen content of the skin.

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OBJECTIVES: To determine plasma CoQ(10) concentration in the course of gestational diabetes mellitus. STUDY DESIGN: The assessment was provided longitudinally during the third trimester of pregnancy in 40 women with gestational diabetes mellitus (GDM) and 40 normal controls. CoQ(10) was measured with the HPLC method. CoQ(10) results were also normalized to plasma cholesterol concentration (nmoles/mmoles). Plasma samples were collected longitudinally throughout the third trimester. RESULTS: No statistically significant difference of plasma CoQ(10)/cholesterol levels between GDM patients and controls at 28-32 and 32-36 weeks of gestation, this difference was significant in late pregnancy (36-40 weeks), similarly, in the same gestational period, there was an increased level of HOMA-IR as index of insulin resistance ORAC as index of oxidative stress. CONCLUSIONS: Since coenzyme Q(10) is believed to be an important cellular antioxidant defence, higher levels of CoQ(10) in GDM patients may be a compensatory mechanism, in response to an activated oxidative stress, probably associated to hyperglycaemia and insulin resistance.

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Menaquinone-7 (MK-7), a member of the vitamin K2 family, performs several functions, all related to its recognised effect on post-translational carboxylation of certain protein-bound glutamate residues. Due to its lipophilic structure MK-7 is soluble in olive oil, so the aim of the present study was to test whether extra-virgin (EV) olive oil enriched with MK-7 significantly increases MK-7 plasma levels and has an effect on osteocalcin and its carboxylation status. Healthy young volunteers (n 12) were administered 20 ml EV olive oil per d for 2 weeks, followed by 2 weeks of the same amount of olive oil enriched with 45 µg and then 90 µg MK-7, with an appropriate washout time in between. Blood was collected and plasma separated in each phase of the study. We found that integration of the diet with EV olive oil alone did not produce any significant variation of MK-7 plasma levels compared with baseline. Supplementation with MK-7-enriched olive oil resulted in a significant and dose-dependent increase in plasma levels. The high dose also significantly increased carboxylated osteocalcin (cOC) and decreased undercarboxylated osteocalcin (ucOC) plasma levels, resulting in a significant increase in the cOC:ucOC ratio. A significant correlation was also found between percentage variation of plasma cOCA:ucOC ratio and increase in plasma MK-7 levels. We conclude that regular consumption of MK-7-enriched olive oil may constitute a valid approach in order to preserve some key biochemical mechanisms controlling bone mineralisation.

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Since the time a precise role of coenzyme Q(10) (CoQ(10) ) in myocardial bioenergetics was established, the involvement of CoQ in the pathophysiology of heart failure was hypothesized. This provided the rationale for numerous clinical trials of CoQ(10) as adjunctive treatment for heart failure. A mild hypotensive effect of CoQ was reported in the early years of clinical use of this compound. We review early human and animal studies on the vascular effects of CoQ. We then focus on endothelial dysfunction in type 2 diabetes and the possible impact on this condition of antioxidants and nutritional supplements, and in particular the therapeutic effects of CoQ. The effect of CoQ(10) on endothelial dysfunction in ischemic heart disease is also reviewed together with recent data highlighting that treatment with CoQ(10) increases extracellular SOD activity.

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Coenzyme Q(10) (CoQ(10)), also known as ubiquinone for its presence in all body cells, is an essential part of the cell energy-producing system. However, it is also a powerful lipophilic antioxidant protecting lipoproteins and cell membranes. Due to these two actions, CoQ(10) is commonly used in clinical practice in chronic heart failure, male infertility, and neurodegenerative disease. However, it is also taken as an anti-aging substance by healthy people aiming for long-term neuroprotection and by sportsmen to improve endurance. Many hormones are known to be involved in body energy regulation, in terms of production, consumption and dissipation, and their influence on CoQ(10) body content or blood values may represent an important pathophysiological mechanism. We summarize the main findings of the literature about the link between hormonal systems and circulating CoQ(10) levels. In particular the role of thyroid hormones, directly involved in the regulation of energy homeostasis, is discussed. There is also a link with gonadal and adrenal hormones, partially due to the common biosynthetic pathway with CoQ(10), but also to the increased oxidative stress found in hypogonadism and hypoadrenalism.

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Impaired functions of myocardial muscle cells in human and animals, is a primary defect associated with idiopathic dilated cardiomyopathy (DCM). The pathophysiological mechanisms implicated in the DCM are yet to be clarified and an effective therapy is still not available. The BIO TO-2 cardiomyopathic Syrian Hamsters (CMSHs) represent an animal model of idiopathic DCM. The aim of this study was to investigate the effect of long-term treatment (2 months) with propionyl-L-carnitine (PLC), coenzyme Q(10), omega-3 fatty acids and a combination of these three agents (formulation HS12607) on mechanical properties and acto-myosin crossbridges (CBs) kinetics of left ventricular (LV) papillary muscle from control and treated 10 month old BIO TO-2 CMSHs. Isometric and isotonic contractile properties of isolated papillary muscle from control and treated CMSHs were investigated, and acto-myosin CB number, force and kinetics were calculated using Huxley's equations. Mechanical parameter values were higher in treated than in control hamsters, particularly when substances were administered together in a coformulation (HS12607). Compared to control, HS12607-treated papillary muscles showed a significant increase of maximum peak isometric tension (P(o)) (30.06 +/- 4.91 vs. 19.74 +/- 5.00 mN/mm(2)), maximum extent of muscle shortening (0.13 +/- 0.03 vs. 0.07 +/- 0.02 L/L(max)), maximum unloaded shortening velocity (1.18 +/- 0.24 vs. 0.53 +/- 0.13 L/L(max) s(-1)) and maximum peak of power output (5.52 +/- 1.61 vs. 1.58 +/- 0.83). The curvature of the hyperbolic force-velocity relationships did not differ between control and treated hamsters. When compared to controls, acto-myosin CB number increased in treated hamsters [(6.67 +/- 1.91) 10(10)/mm(2) vs. (3.55 +/- 2.08) 10(10)/mm(2)], whereas the unitary force of single CB was similar in control and treated animals. The peak value of the rate constant for CB attachment (f(1)) and detachment (g(2)) was higher in treated animals when compared to control. (93.87 +/- 25.82 vs.47.28 +/- 10.88 s(-1) and 214.40 +/- 44.64 vs. 95.56 +/- 23.49 s(-1), respectively). In conclusion, the present study illustrates that supplementation with PLC, CoQ(10) and omega-3 fatty acids improved motor parameters, energetic, and CB kinetics of BIO TO-2 CMSH papillary muscle indicating that these naturally occurring substances may be a valid adjuvant to conventional therapy in DCM.

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The fundamental role of coenzyme Q(10) (CoQ(10)) in mitochondrial bioenergetics and its well-acknowledged antioxidant properties constitute the basis for its clinical applications, although some of its effects may be related to a gene induction mechanism. Cardiovascular disease is still the main field of study and the latest findings confirm a role of CoQ(10) in improving endothelial function. The possible relation between CoQ(10) deficiency and statin side effects is highly debated, particularly the key issue of whether CoQ(10) supplementation counteracts statin myalgias. Furthermore, in cardiac patients, plasma CoQ(10) was found to be an independent predictor of mortality. Studies on CoQ(10) and physical exercise have confirmed its effect in improving subjective fatigue sensation and physical performance and in opposing exercise-related damage. In the field of mitochondrial myopathies, primary CoQ(10) deficiencies have been identified, involving different genes of the CoQ(10) biosynthetic pathway; some of these conditions were found to be highly responsive to CoQ(10) administration. The initial observations of CoQ(10) effects in Parkinson's and Huntington's diseases have been extended to Friedreich's ataxia, where CoQ(10) and other quinones have been tested. CoQ(10) is presently being used in a large phase III trial in Parkinson's disease. CoQ(10) has been found to improve sperm count and motility on asthenozoospermia. Moreover, for the first time CoQ(10) was found to decrease the incidence of preeclampsia in pregnancy. The ability of CoQ(10) to mitigate headache symptoms in adults was also verified in pediatric and adolescent populations.

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Extracellular superoxide dismutase (SOD3) is the primary enzymatic antioxidant defence of the vascular wall. The physiopathological role of SOD3 has been examined in vascular-related diseases, atherosclerosis, hypertension, diabetes, ischaemia-reperfusion injury, lung disease, various inflammatory conditions, and neurological diseases. An important single nucleotide polymorphism (SNP), nt.760 G>C of the SOD3 gene (rs#1799895) leads to the amino acid substitution Arg(213)Gly (R213G) in the center of the heparin-binding domain and consequently to a lowered affinity for the endothelium. This mutation, which occurs with a relatively high frequency in the population (4% of Swedish, 3% of Australian and 6% of Japanese people), is associated with decreased tissue antioxidant defences and increased risk of ischaemic heart disease. The identification of patients carrying this mutation is therefore of great interest in order to highlight lowered antioxidant defences at a vascular level which could lead to increased susceptibility toward coronary artery disease and atherogenesis. Here we describe a method to detect the 760 G>C single nucleotide polymorphism based on Real Time PCR strategy using locked nucleic acid (LNA) probes. This technique, a modification of classic TaqMan probes SNP genotyping, amplifies and detects the mutation in a single reaction tube. Moreover, the implementation of LNA probes remarkably increases the specificity of the reaction. The proposed method enables unambigous and rapid discrimination of wild type and mutant genotype both in plasmid and genomic DNA samples. In light of the role of SOD3 polymorphism, the genotyping of 760 G>C mutant has important clinical implications. The proposed assay combines rapidity, high specificity, can be easily automated and overall reduces labor and cost of analyses. Moreover, identification of patients with lowered vascular antioxidant defences could address pharmacogenomical approaches to the therapy of cardiovascular diseases.

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Two-electron reduction of quinones catalyzed by NAD(P)H:quinone oxidoreductase (NQO1) protects cells against oxidative stress and toxic quinones. In fact, low level of NQO1 activity is often associated with increased risk of developing different types of tumours and with toxic effects linked to environmental quinones. In a previous report we analyzed the relationship between the oxidative stress induced by UV radiation and CoQ10 content in Burkitt's lymphoma cell lines compared to HL-60. The basal content of CoQ10 in Raji cells was slightly higher compared to HL-60. Moreover, after irradiation or ubiquinone supplementation in the medium, reduced CoQ10 levels were higher in Raji and Daudi cells compared to HL-60. In the present work, in order to inquire if NQO1 plays a role in the CoQ reducing capacity observed in the lymphoblastoid cell lines, we analyzed the transcription and translation products of this gene in Raji and Daudi cells, compared to cell lines possessing low and high NQO1 activity. The amount of transcripts of this gene in lymphoblastoid cells was comparable to that observed in HL-60 cells (low activity), as well as the level of two alternatively spliced mRNAs; one of which is described for the first time in this work. From the genotype analysis of polymorphisms C609T and C465T we observed that HL-60, Raji and Daudi cells were all heterozygous. Furthermore, NQO1 enzyme activity and protein synthesis in the cytosol of Raji and Daudi cells were undetectable. Therefore in Burkitt's lymphoma cell lines the NQO1 gene is not efficiently translated and this effect is not related to (C609T) polymorphism. Further studies will be necessary to find the enzyme responsible for CoQ10 reducing activity observed in lymphoma cell lines. On the other hand, this result suggests a careful re-evaluation of data concerning loss of NQO1 activity and polymorphisms in tumour cells.

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