Effects of inhibiting CoQ10 biosynthesis with 4-nitrobenzoate in human fibroblasts.

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Catarina M Quinzii

Full Text Available Coenzyme Q(10 (CoQ(10 is a potent lipophilic antioxidant in cell membranes and a carrier of electrons in the mitochondrial respiratory chain. We previously characterized the effects of varying severities of CoQ(10 deficiency on ROS production and mitochondrial bioenergetics in cells harboring genetic defects of CoQ(10 biosynthesis. We observed a unimodal distribution of ROS production with CoQ(10 deficiency: cells with <20% of CoQ(10 and 50-70% of CoQ(10 did not generate excess ROS while cells with 30-45% of CoQ(10 showed increased ROS production and lipid peroxidation. Because our previous studies were limited to a small number of mutant cell lines with heterogeneous molecular defects, here, we treated 5 control and 2 mildly CoQ(10 deficient fibroblasts with varying doses of 4-nitrobenzoate (4-NB, an analog of 4-hydroxybenzoate (4-HB and inhibitor of 4-para-hydroxybenzoate:polyprenyl transferase (COQ2 to induce a range of CoQ(10 deficiencies. Our results support the concept that the degree of CoQ(10 deficiency in cells dictates the extent of ATP synthesis defects and ROS production and that 40-50% residual CoQ(10 produces maximal oxidative stress and cell death.

Coenzyme Q10 and alpha-tocopherol protect against amitriptyline toxicity

International Nuclear Information System (INIS)

Cordero, Mario D.; Moreno-Fernandez, Ana Maria; Gomez-Skarmeta, Jose Luis; Miguel, Manuel de; Garrido-Maraver, Juan; Oropesa-Avila, Manuel; Rodriguez-Hernandez, Angeles; Navas, Placido; Sanchez-Alcazar, Jose Antonio

2009-01-01

Since amitriptyline is a very frequently prescribed antidepressant drug, it is not surprising that amitriptyline toxicity is relatively common. Amitriptyline toxic systemic effects include cardiovascular, autonomous nervous, and central nervous systems. To understand the mechanisms of amitriptyline toxicity we studied the cytotoxic effects of amitriptyline treatment on cultured primary human fibroblasts and zebrafish embryos, and the protective role of coenzyme Q 10 and alpha-tocopherol, two membrane antioxidants. We found that amitriptyline treatment induced oxidative stress and mitochondrial dysfunction in primary human fibroblasts. Mitochondrial dysfunction in amitriptyline treatment was characterized by reduced expression levels of mitochondrial proteins and coenzyme Q 10 , decreased NADH:cytochrome c reductase activity, and a drop in mitochondrial membrane potential. Moreover, and as a consequence of these toxic effects, amitriptyline treatment induced a significant increase in apoptotic cell death activating mitochondrial permeability transition. Coenzyme Q 10 and alpha-tocopherol supplementation attenuated ROS production, lipid peroxidation, mitochondrial dysfunction, and cell death, suggesting that oxidative stress affecting cell membrane components is involved in amitriptyline cytotoxicity. Furthermore, amitriptyline-dependent toxicity and antioxidant protection were also evaluated in zebrafish embryos, a well established vertebrate model to study developmental toxicity. Amitriptyline significantly increased embryonic cell death and apoptosis rate, and both antioxidants provided a significant protection against amitriptyline embryotoxicity

The Antioxidant Status and Concentrations of Coenzyme Q10 and Vitamin E in Metabolic Syndrome

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Chi-Hua Yen

2013-01-01

Full Text Available The purpose of this study was to investigate the levels of coenzyme Q10 and vitamin E and the antioxidant status in subjects with metabolic syndrome (MS. Subjects with MS (n=72 were included according to the criteria for MS. The non-MS group (n=105 was comprised of healthy individuals with normal blood biochemical values. The plasma coenzyme Q10, vitamin E concentrations, lipid profiles, and antioxidant enzymes levels (catalase, superoxide dismutase, and glutathione peroxidase were measured. The subjects with MS had significantly higher concentrations of plasma coenzyme Q10 and vitamin E than those in the non-MS group, but these differences were not significant after being normalized for triglyceride level. The levels of antioxidant enzymes were significantly lower in the MS group than in the non-MS group. The subjects with the higher antioxidant enzymes activities had significant reductions in the risk of MS (P<0.01 after being adjusted for coenzyme Q10 and vitamin E. In conclusion, the subjects with MS might be under higher oxidative stress resulting in low levels of antioxidant enzyme activities. A higher level of antioxidant enzymes activities was significantly associated with a reduction in the risk of MS independent of the levels of coenzyme Q10 and vitamin E.

Genetics Home Reference: primary coenzyme Q10 deficiency

Science.gov (United States)

... mutations have occurred in the COQ2 , COQ4 , COQ6 , COQ8A , and COQ8B genes. Smaller numbers of mutations in other COQ genes have also been found ... primary coenzyme Q10 deficiency ... Related Information What is a gene? What is a gene mutation and how do mutations occur? How can gene ...

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q(10), and creatine.

Science.gov (United States)

Purchas, R W; Rutherfurd, S M; Pearce, P D; Vather, R; Wilkinson, B H P

2004-03-01

Levels of taurine, carnosine, coenzyme Q(10), and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q(10) is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q(10), but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q(10) and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine (Plamb, but that these levels vary between muscles, between animals, and with cooking.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

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Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

2018-02-07

The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency.

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Lagier-Tourenne, Clotilde; Tazir, Meriem; López, Luis Carlos; Quinzii, Catarina M; Assoum, Mirna; Drouot, Nathalie; Busso, Cleverson; Makri, Samira; Ali-Pacha, Lamia; Benhassine, Traki; Anheim, Mathieu; Lynch, David R; Thibault, Christelle; Plewniak, Frédéric; Bianchetti, Laurent; Tranchant, Christine; Poch, Olivier; DiMauro, Salvatore; Mandel, Jean-Louis; Barros, Mario H; Hirano, Michio; Koenig, Michel

2008-03-01

Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ(10) biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ(10) deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ(10) in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production.

Hepatoprotective effect of taurine and coenzyme Q10 and their ...

African Journals Online (AJOL)

stress in rats. Afaf Abbass Sayed ... Keywords: Taurine, Coenzyme Q10, Acrylamide, Oxidative stress, Biochemical profile, ... uses, AA formation in foods has its major routes through .... release of serum inflammatory markers and neutrophil ...

Coenzyme Q10 protects hair cells against aminoglycoside.

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Kazuma Sugahara

Full Text Available It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10 is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group. In the neomycin group, utricles were cultured with neomycin (1 mM to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM. Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

Role of coenzyme Q10 (CoQ10) in cardiac disease, hypertension and Meniere-like syndrome.

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Kumar, Adarsh; Kaur, Harharpreet; Devi, Pushpa; Mohan, Varun

2009-12-01

Coenzyme Q10 (ubiquinone) is a mitochondrial coenzyme which is essential for the production of ATP. Being at the core of cellular energy processes it assumes importance in cells with high energy requirements like the cardiac cells which are extremely sensitive to CoQ10 deficiency produced by cardiac diseases. CoQ10 has thus a potential role for prevention and treatment of heart ailments by improving cellular bioenergetics. In addition it has an antioxidant, a free radical scavenging and a vasodilator effect which may be helpful in these conditions. It inhibits LDL oxidation and thus the progression of atherosclerosis. It decreases proinflammatory cytokines and decreases blood viscosity which is helpful in patients of heart failure and coronary artery disease. It also improves ischemia and reperfusion injury of coronary revascularisation. Significant improvement has been observed in clinical and hemodynamic parameters and in exercise tolerance in patients given adjunctive CoQ10 in doses from 60 to 200 mg daily in the various trials conducted in patients of heart failure, hypertension, ischemic heart disease and other cardiac illnesses. Recently it has been found to be an independent predictor of mortality in congestive heart failure. It has also been found to be helpful in vertigo and Meniere-like syndrome by improving the immune system. Further research is going on to establish firmly its role in the therapy of cardiovascular diseases.

Coenzyme Q10 supplementation and exercise-induced oxidative stress in humans

DEFF Research Database (Denmark)

Östman, Bengt; Sjödin, Anders Mikael; Michaëlsson, Karl

2012-01-01

Objective: The theoretically beneficial effects of coenzyme Q10 (Q10) on exercise-related oxidative stress and physical capacity have not been confirmed to our knowledge by interventional supplementation studies. Our aim was to investigate further whether Q10 supplementation at a dose recommended...... the groups were detected for hypoxanthine or uric acid (serum markers of oxidative stress) or creatine kinase (a marker of skeletal muscle damage). Conclusion: Although in theory Q10 could be beneficial for exercise capacity and in decreasing oxidative stress, the present study could not demonstrate...

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

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Ates, Orhan; Bilen, Habip; Keles, Sadullah; Alp, H. Hakan; Keleş, Mevlüt Sait; Yıldırım, Kenan; Öndaş, Osman; Pınar, L. Can; Civelekler, Mustafa; Baykal, Orhan

2013-01-01

AIM To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy. PMID:24195048

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

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Orhan Ates

2013-10-01

Full Text Available AIM: To determine the relationship between proliferative diabetic retinopathy (PDRP and plasma coenzyme Q10(CoQ10 concentration.METHODS: Patients with type 2 diabetes and PDRP were determined to be the case group (n=50. The control group was consist of healthy individuals (n=50. Plasma CoQ10 and malondialdehyde (MDA levels were measured in both groups.RESULTS: Ubiquinone-10 (Coenzyme Q10 levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively.CONCLUSION:The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy.

Antiatherogenic, hepatoprotective, and hypolipidemic effects of coenzyme Q10 in alloxan-induced type 1 diabetic rats

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Hassan Ahmadvand

2014-07-01

Full Text Available BACKGROUND: Diabetes mellitus, one of the leading metabolic syndromes, accounts for highest morbidity and mortality worldwide. In this study, we examined possible protective effect of coenzyme Q10 on lipid profile, atherogenic index, and liver enzyme markers in alloxan-induced type 1 diabetic rats. METHODS: A total of 30 male rats were randomly divided into three groups; group 1 as control, group 2 diabetic untreatment, and group 3 treatments with coenzyme Q10 by 15 mg/kg i.p. daily, respectively .Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After 8 weeks, the levels of fasting blood glucose (FBG, triglyceride (TG, total cholesterol (TC, low density lipoprotein (LDL, very low-density lipoprotein (VLDL, high density lipoprotein (HDL, atherogenic index, atherogenic coefficient, cardiac risk ratio, and the activities of alanine aminotransferase (ALT, aspartate aminotransferase (AST, and alkaline phosphatase (ALP of all groups were analyzed. Data were analyzed using non-parametric Mann-Whitney test (using SPSS and P < 0.05 was considered as significant. RESULTS: Coenzyme Q10 inhibited significantly the activities of ALT (11.17%, AST (19.35% and ALP (36.67% and decreased FBG (21.19%, TG (37.24%, TC (17.15%, LDL (30.44%, VLDL (37.24%, atherogenic index (44.24%, atherogenic coefficient (49.69%, and cardiac risk ratio (37.97%, HDL level was significantly (33.38% increased when treated with coenzyme Q10. CONCLUSION: The findings of this study suggest that coenzyme Q10 exert beneficial effects on the lipid profile, atherogenic index, and liver enzymes activity in alloxan-induced type 1 diabetic rats.   Keywords: Diabetes, Lipid Profile, Atherogenic Index, Rats, Liver Enzymes, Coenzyme Q10 

Topical treatment with coenzyme Q10-containing formulas improves skin's Q10 level and provides antioxidative effects.

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Knott, Anja; Achterberg, Volker; Smuda, Christoph; Mielke, Heiko; Sperling, Gabi; Dunckelmann, Katja; Vogelsang, Alexandra; Krüger, Andrea; Schwengler, Helge; Behtash, Mojgan; Kristof, Sonja; Diekmann, Heike; Eisenberg, Tanya; Berroth, Andreas; Hildebrand, Janosch; Siegner, Ralf; Winnefeld, Marc; Teuber, Frank; Fey, Sven; Möbius, Janne; Retzer, Dana; Burkhardt, Thorsten; Lüttke, Juliane; Blatt, Thomas

2015-01-01

Ubiquinone (coenzyme Q10, Q10) represents an endogenously synthesized lipid-soluble antioxidant which is crucial for cellular energy production but is diminished with age and under the influence of external stress factors in human skin. Here, it is shown that topical Q10 treatment is beneficial with regard to effective Q10 replenishment, augmentation of cellular energy metabolism, and antioxidant effects. Application of Q10-containing formulas significantly increased the levels of this quinone on the skin surface. In the deeper layers of the epidermis the ubiquinone level was significantly augmented indicating effective supplementation. Concurrent elevation of ubiquinol levels suggested metabolic transformation of ubiquinone resulting from increased energy metabolism. Incubation of cultured human keratinocytes with Q10 concentrations equivalent to treated skin showed a significant augmentation of energy metabolism. Moreover, the results demonstrated that stressed skin benefits from the topical Q10 treatment by reduction of free radicals and an increase in antioxidant capacity. © 2015 International Union of Biochemistry and Molecular Biology.

Coenzyme Q10 supplementation decreases statin-related mild-to-moderate muscle symptoms: a randomized clinical study.

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Skarlovnik, Ajda; Janić, Miodrag; Lunder, Mojca; Turk, Martina; Šabovič, Mišo

2014-11-06

Statin use is frequently associated with muscle-related symptoms. Coenzyme Q10 supplementation has yielded conflicting results in decreasing statin myopathy. Herein, we tested whether coenzyme Q10 supplementation could decrease statin-associated muscular pain in a specific group of patients with mild-to-moderate muscle symptoms. Fifty patients treated with statins and reporting muscle pain were recruited. The Q10 group (n=25) received coenzyme Q10 supplementation over a period of 30 days (50 mg twice daily), and the control group (n=25) received placebo. The Brief Pain Inventory (BPI) questionnaire was used and blood testing was performed at inclusion in the study and after 30 days of supplementation. The intensity of muscle pain, measured as the Pain Severity Score (PSS), in the Q10 group was reduced from 3.9±0.4 to 2.9±0.4 (PPain Interference Score (PIS) after Q10 supplementation was reduced from 4.0±0.4 to 2.6±0.4 (Pstatin-related muscle symptoms in 75% of patients. The relative values of PSS and PIS significantly decreased (-33.1% and -40.3%, respectively) in the Q10 group compared to placebo group (both Pmuscle enzymes or cholesterol values were found. The present results show that coenzyme Q10 supplementation (50 mg twice daily) effectively reduced statin-related mild-to-moderate muscular symptoms, causing lower interference of statin-related muscular symptoms with daily activities.

Exogenous coenzyme Q10 modulates MMP-2 activity in MCF-7 cell line as a breast cancer cellular model

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Mirmiranpour Hossein

2010-11-01

Full Text Available Abstract Background/Aims Matrix Metalloproteinases 2 is a key molecule in cellular invasion and metastasis. Mitochondrial ROS has been established as a mediator of MMP activity. Coenzyme Q10 contributes to intracellular ROS regulation. Coenzyme Q10 beneficial effects on cancer are still in controversy but there are indications of Coenzyme Q10 complementing effect on tamoxifen receiving breast cancer patients. Methods In this study we aimed to investigate the correlation of the effects of co-incubation of coenzyme Q10 and N-acetyl-L-cysteine (NAC on intracellular H2O2 content and Matrix Metalloproteinase 2 (MMP-2 activity in MCF-7 cell line. Results and Discussion Our experiment was designed to assess the effect in a time and dose related manner. Gelatin zymography and Flowcytometric measurement of H2O2 by 2'7',-dichlorofluorescin-diacetate probe were employed. The results showed that both coenzyme Q10 and N-acetyl-L-cysteine reduce MMP-2 activity along with the pro-oxidant capacity of the MCF-7 cell in a dose proportionate manner. Conclusions Collectively, the present study highlights the significance of Coenzyme Q10 effect on the cell invasion/metastasis effecter molecules.

A randomized controlled trial of coenzyme Q10 for fatigue in the late-onset sequelae of poliomyelitis.

Science.gov (United States)

Peel, Margaret M; Cooke, Marie; Lewis-Peel, Helen J; Lea, Rodney A; Moyle, Wendy

2015-12-01

To determine if coenzyme Q(10) alleviates fatigue in the late-onset sequelae of poliomyelitis. Parallel-group, randomized, placebo-controlled trial. Coenzyme Q(10) has been shown to boost muscle energy metabolism in post-polio subjects but it does not promote muscle strength, endurance or function in polio survivors with post-poliomyelitis syndrome. However, the collective increased energy metabolism might contribute to a reduction in post-polio fatigue. Polio survivors from the Australian post-polio networks in Queensland and New South Wales who attribute a moderate to high level of fatigue to their diagnosed late-onset sequelae of poliomyelitis. Those with fatigue-associated comorbidities of diabetes, anaemia, hypothyroidism and fibromyalgia were excluded. Participants were assigned (1:1), with stratification of those who use energy-saving mobility aids, to receive 100 mg coenzyme Q(10) or matching placebo daily for 60 days. Participants and investigators were blinded to group allocation. Fatigue was assessed by the Multidimensional Assessment of Fatigue as the primary outcome and the Fatigue Severity Scale as secondary outcome. Of 103 participants, 54 were assigned to receive coenzyme Q(10) and 49 to receive the placebo. The difference in the mean score reductions between the two groups was not statistically significant for either fatigue measure. Oral supplementation with coenzyme Q(10) was safe and well-tolerated. A daily dose of 100 mg coenzyme Q(10) for 60 days does not alleviate the fatigue of the late-onset sequelae of poliomyelitis. The registration number for the clinical trial is ACTRN 12612000552886. Copyright © 2015 Elsevier Ltd. All rights reserved.

Plasma coenzyme Q10 concentrations are not decreased in male patients with coronary atherosclerosis

NARCIS (Netherlands)

Vijver, L.P.L. van de; Weber, C.; Kardinaal, A.F.M.; Grobbee, D.E.; Princen, H.M.G.; Poppel, G. van

1999-01-01

Coenzyme Q10 (CoQ10) is an important mitochondrial electron transfer component and has been postulated to function as a powerful antioxidant protecting LDL from oxidative damage. It could thus reduce the risk of cardiovascular disease. Thus far, beneficial effects of supplementation with CoQ10 have

Coenzyme Q10 prevented full blown splenomegaly and decreased melarsoprol-induced reactive encephalopathy in mice infected with Trypanosoma brucei rhodesiense

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James Nyabuga Nyariki

2015-03-01

Full Text Available Objective: To establish the modulatory effects of coenzyme Q10 on experimental trypanosome infections in mice and evaluate the risk of occurrence and severity of melarsoprol-induced post treatment reactive encephalopathy (PTRE. Methods: Female Swiss white mice were orally administered with 200 mg/kg of coenzyme Q10 after which they were intraperitoneally inoculated with Trypanasoma brucei rhodesiense (T. b. rhodesiense. The resultant infection was allowed to develop and simulate all phases of human African trypanosomiasis and PTRE. Parasitaemia development, packed cell volume, haematological and pathological changes were determined. Results: A histological study in the brain tissue of T. b. rhodesiense infected mice demonstrated neuroinflammatory pathology which was highly amplified in the PTRE-induced groups. A prominent reduction in the severity of the neuroinflammatory response was detected when coenzyme-Q10 was administered. Furthermore, the mean tissue weight of spleen to body ratio in coenzyme Q10 supplemented group was significantly (P<0.05 different compared to un-supplemented groups, and clearly indicated that coenzyme Q10 prevented full blown splenomegaly pathogenesis by T. b. rhodesiense. A significant (P<0.05 increase in hemoglobin levels and red blood cells was observed in coenzyme Q10 mice compared to those infected and un-supplemented with coenzyme Q10. Conclusions: The capacity of coenzyme Q10 to alter the pathogenesis of T. b. rhodesiense infection in mice and following treatment with melarsoprol, may find application by rendering humans and animals less susceptible to deleterious effects of trypanosome infection such as splenomegaly and melarsoprol-induced PTRE and neurotoxicity.

Protective Effect of Coenzyme Q10 on Methamphetamine-Induced Apoptosis in Adult Male Rats

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Fatemeh Gholipour

2017-06-01

Full Text Available Background: The negative consequence of methamphetamine abuse is due to neuropathologic changes in the brain, which reduces dopaminergic neurons and result in damage to different brain areas. Neurotoxicity induced by methamphetamine increases the oxidative stress and associated with neuronal apoptosis. The role of the antioxidant coenzyme Q10 probably produces its neuroprotective effects. Therefore, the purpose of the present study was to examine the protective effect of coenzyme Q10 on methamphetamine-induced apoptosis in adult male rats.Materials and Methods: Fifty Wistar eight-week adult rats randomly divided into 5 groups: Healthy control, methamphetamine injection (Meth, methamphetamine injection and CoQ10 5mg/kg treatment (Meth+Post CoQ10 5mg/kg, methamphetamine injection and CoQ10 10mg/kg treatment (Meth+Post CoQ10 10mg/kg, methamphetamine injection and CoQ10 20mg/kg treatment (Meth+Post CoQ10 20mg/kg. Methamphetamine with a purity of 96% with a dosage of 20 mg/kg was injected Intraperitoneal. Coenzyme Q10 for three treatment groups was injected intraperitoneally for 14 days in a dosage of 5, 10 and 20 mg/kg/day. The protein expressions of Baxand Bcl2 were evaluated by western blotting technique.Results: Bax protein expression was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.010 and so Meth+Post CoQ10 10mg/kg (p=0.004 comparing to Meth group. In addition, Bcl2 protein expression was significantly higher in Meth+Post CoQ10 5mg/kg comparing to Meth group (p=0.018. However, there were no significant differences between control and CoQ10 treatment groups. Bax/Bcl2 ratio was significantly lower in Meth+Post CoQ10 5mg/kg (p=0.005, Meth+Post CoQ10 10mg/kg (p=0.008 and Meth+Post CoQ10 20mg/kg (p=0.044 comparing to Meth group.Conclusion: We suggest that CoQ10 reduces the methamphetamine-induced apoptosis in the striatum of the rats through the reduction of apoptotic factors and increase of anti-apoptotic pathways.

Coenzyme Q10: A New Treatment for Hemorrhagic Shock

Science.gov (United States)

2014-10-29

SUBJECT TERMS hemorrhagic shock, ubiquinol, Coenzyme Q10, patient outcome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...o leo& to tboOigllll failure. The < Iota fur AlM •1 ha"’ boon ._...runym.,..,; •• ted in p=en~atlons and publiobed tn Expu""’""" P/u<llology. Tho

Therapeutic implication of coenzyme Q10 during statin therapy: pros and cons

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Mir-Jamal Hosseini

2015-09-01

Full Text Available Coenzyme Q10 (CoQ10 is a vitamin-like substance, and a natural intermediate of electron transport chain (ETC of mitochondria which can accepts and donates electrons from complex I and complex II. CoQ10 shares a biosynthetic pathway with cholesterol and dolichol thus it can be a potential target of the widely available lipid-lowering drugs. The lipid lowering drugs such as statins, are widely administered to individuals who have high cholesterol levels. This article reviews the a clinical benefits of CoQ10 b association between administration of statin and CoQ10 deficiency and c involvement of CoQ10 in statin-associated myopathy.

Potential role of coenzyme Q10 in health and disease conditions

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Rodick TC

2018-02-01

Full Text Available Taylor C Rodick,1 Donna R Seibels,2 Jeganathan Ramesh Babu,1 Kevin W Huggins,1 Guang Ren,3 Suresh T Mathews2 1Department of Nutrition, Dietetics, & Hospitality Management, Auburn University, Auburn, 2Department of Nutrition and Dietetics, Samford University, 3Medicine-Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Coenzyme Q10 (CoQ10, an endogenously produced compound, is found in all human cells. Within the mitochondria, it plays a substantial role in energy production by acting as a mobile electron carrier in the electron transport chain. Outside the mitochondria, it acts as an excellent antioxidant by sequestering free radicals and working synergistically with other antioxidants, including vitamin E. Dietary contribution is limited, making endogenous production the primary source for optimal function. Now widely available as an over-the-counter supplement, CoQ10 has gained attention for its possible therapeutic use in minimizing the outcomes of certain metabolic diseases, notably cardiovascular disease, diabetes, neurodegenerative disease, and cancer. Research has shown positive results in subjects supplemented with CoQ10, especially in relation to upregulating antioxidant capability. Emerging research suggests beneficial effects of CoQ10 supplementation in individuals on statin medications. CoQ10 supplementation in individuals participating in strenuous exercise seems to exert some beneficial effects, although the data are conflicting with other types of physical activity. This broad review of current CoQ10 literature, while outlining its physiological/functional significance in health and disease conditions, also offers a dietitian’s perspective on its potential use as a supplement in the promotion of health and management of disease conditions. Keywords: coenzyme Q, antioxidant, oxidative stress, dietary supplement, statin

Effects of ubiquinone (coenzyme Q10) on myopathy in statin users.

NARCIS (Netherlands)

Schaars, C.F.; Stalenhoef, A.F.H.

2008-01-01

PURPOSE OF REVIEW: Statins are associated with muscle complaints, including myositis. The mechanism through which statin use causes muscle toxicity is unknown. One of the theories is that statin therapy reduces coenzyme Q10 levels in muscle mitochondria, which leads to muscle injury and myopathy.

Genetic Rescue of Mitochondrial and Skeletal Muscle Impairment in an Induced Pluripotent Stem Cells Model of Coenzyme Q10 Deficiency.

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Romero-Moya, Damià; Santos-Ocaña, Carlos; Castaño, Julio; Garrabou, Gloria; Rodríguez-Gómez, José A; Ruiz-Bonilla, Vanesa; Bueno, Clara; González-Rodríguez, Patricia; Giorgetti, Alessandra; Perdiguero, Eusebio; Prieto, Cristina; Moren-Nuñez, Constanza; Fernández-Ayala, Daniel J; Victoria Cascajo, Maria; Velasco, Iván; Canals, Josep Maria; Montero, Raquel; Yubero, Delia; Jou, Cristina; López-Barneo, José; Cardellach, Francesc; Muñoz-Cánoves, Pura; Artuch, Rafael; Navas, Plácido; Menendez, Pablo

2017-07-01

Coenzyme Q 10 (CoQ 10 ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ 10 biosynthesis (COQ genes) cause primary CoQ 10 deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype-phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c.483G > C (E161D)) in COQ4. The patient's fibroblasts showed a decrease in [CoQ 10 ], CoQ 10 biosynthesis, MRC activity affecting complexes I/II + III, and respiration defects. Bona fide induced pluripotent stem cell (iPSCs) lines carrying the COQ4 mutation (CQ4-iPSCs) were generated, characterized and genetically edited using the CRISPR-Cas9 system (CQ4 ed -iPSCs). Extensive differentiation and metabolic assays of control-iPSCs, CQ4-iPSCs and CQ4 ed -iPSCs demonstrated a genotype association, reproducing the disease phenotype. The COQ4 mutation in iPSC was associated with CoQ 10 deficiency, metabolic dysfunction, and respiration defects. iPSC differentiation into SkM was compromised, and the resulting SkM also displayed respiration defects. Remarkably, iPSC differentiation in dopaminergic or motor neurons was unaffected. This study offers an unprecedented iPSC model recapitulating CoQ 10 deficiency-associated functional and metabolic phenotypes caused by COQ4 mutation. Stem Cells 2017;35:1687-1703. © 2017 AlphaMed Press.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects.

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Zaki, Moushira E; El-Bassyouni, Hala T; Tosson, Angie M S; Youness, Eman; Hussein, Jihan

Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Eighty-six children (5-8 years of age) were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014). Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p=0.002), while coenzyme Q10 was significantly decreased (p=0.002). Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects

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Moushira E. Zaki

Full Text Available Abstract: Objective: Evidence of oxidative stress was reported in individuals with Down syndrome. There is a growing interest in the contribution of the immune system in Down syndrome. The aim of this study is to evaluate the coenzyme Q10 and selected pro-inflammatory markers such as interleukin 6 and tumor necrosis factor α in children with Down syndrome. Methods: Eighty-six children (5-8 years of age were enrolled in this case-control study from two public institutions. At the time of sampling, the patients and controls suffered from no acute or chronic illnesses and received no therapies or supplements. The levels of interleukin 6, tumor necrosis factor α, coenzyme Q10, fasting blood glucose, and intelligence quotient were measured. Results: Forty-three young Down syndrome children and forty-three controls were included over a period of eight months (January-August 2014. Compared with the control group, the Down syndrome patients showed significant increase in interleukin 6 and tumor necrosis factor α (p = 0.002, while coenzyme Q10 was significantly decreased (p = 0.002. Also, body mass index and fasting blood glucose were significantly increased in patients. There was a significantly positive correlation between coenzyme Q10 and intelligence quotient levels, as well as between interleukin 6 and tumor necrosis factor α. Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Micronutrient special issue: Coenzyme Q10 requirements for DNA damage prevention

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Schmelzer, Constance; Döring, Frank

2012-01-01

Coenzyme Q 10 (CoQ 10 ) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ 10 (ubiquinol, Q 10 H 2 ) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ 10 supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ 10 on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ 10 provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ 10 on oxidative stress biomarkers, CoQ 10 intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ 10 on prevention of DNA damage.

LC/MS/MS analysis of α-tocopherol and coenzyme Q10 content in lyophilized royal jelly, beebread and drone homogenate.

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Hryniewicka, Marta; Karpinska, Agnieszka; Kijewska, Marta; Turkowicz, Monika Joanna; Karpinska, Joanna

2016-11-01

This study shows the results of application liquid chromatography-tandem mass spectrometry (LC/MS/MS) for assay of the content of α-tocopherol and coenzyme Q 10 in bee products of animal origin, i.e. royal jelly, beebread and drone homogenate. The biological matrix was removed using extraction with n-hexane. It was found that drone homogenate is a rich source of coenzyme Q 10 . It contains only 8 ± 1 µg/g of α-tocopherol and 20 ± 2 µg/g of coenzyme Q 10 . The contents of assayed compounds in royal jelly were 16 ± 3 and 8 ± 0.2 µg/g of α-tocopherol and coenzyme Q 10 , respectively. Beebread appeared to be the richest of α-tocopherol. Its level was 80 ± 30 µg/g, while the level of coenzyme Q 10 was only 11.5 ± 0.3 µg/g. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Protective Effects of Alpha-Lipoic Acid and Coenzyme Q10 Combination on Ovarian Ischemia-Reperfusion Injury: An Experimental Study

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Ahmet Ali Tuncer

2016-01-01

Full Text Available Objective. This study aims to evaluate whether alpha-lipoic acid and/or coenzyme Q10 can protect the prepubertal ovarian tissue from ischemia-reperfusion injury in an experimental rat model of ovarian torsion. Materials and Methods. Forty-two female preadolescent Wistar-Albino rats were divided into 6 equal groups randomly. The sham group had laparotomy without torsion; the other groups had torsion/detorsion procedure. After undergoing torsion, group 2 received saline, group 3 received olive oil, group 4 received alpha-lipoic acid, group 5 received coenzyme Q10, and group 6 received both alpha-lipoic acid and coenzyme Q10 orally. The oxidant-antioxidant statuses of these groups were compared using biochemical measurement of oxidized/reduced glutathione, glutathione peroxidase and malondialdehyde, pathological evaluation of damage and apoptosis within the ovarian tissue, and immunohistochemical assessment of nitric oxide synthase. Results. The left ovaries of the alpha-lipoic acid + coenzyme Q10 group had significantly lower apoptosis scores and significantly higher nitric oxide synthase content than the left ovaries of the control groups. The alpha-lipoic acid + coenzyme Q10 group had significantly higher glutathione peroxidase levels and serum malondialdehyde concentrations than the sham group. Conclusions. The combination of alpha-lipoic acid and coenzyme Q10 has beneficial effects on oxidative stress induced by ischemia-reperfusion injury related to ovarian torsion.

Hormonal Influence on Coenzyme Q10 Levels in Blood Plasma

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Alfredo Pontecorvi

2011-12-01

Full Text Available Coenzyme Q10 (CoQ10, 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, CoQ10 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 CoQ10 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 CoQ10 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 CoQ10, but also to the increased oxidative stress found in hypogonadism and hypoadrenalism.

Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal death by chronic Coenzyme Q10 pretreatment

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Binukumar, BK; Gupta, Nidhi; Bal, Amanjit; Gill, Kiran Dip

2011-01-01

Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q 10 (CoQ 10 ) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, α-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, α-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q 10 (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q 10 administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, α-synuclein aggregation and motor dysfunction by virtue of its antioxidant action. - Highlights: → CoQ 10 administration attenuates dichlorvos induced nigrostriatal neurodegenaration. → CoQ 10 pre treatment leads to preservation of TH-IR neurons. → CoQ 10 may decrease oxidative damage and α-synuclin aggregation. → CoQ 10 treatment enhances motor function and protects rats from catalepsy.

Design, optimization and characterization of coenzyme Q10- and D-panthenyl triacetate-loaded liposomes

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Çelik B

2017-07-01

Full Text Available Burak Çelik,1 Ali Asram Sağıroğlu,1 Samet Özdemir2 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Bezmialem Vakif University, 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Yeditepe University, Istanbul, Turkey Abstract: Coenzyme Q10 (CoQ10 is a lipid-soluble molecule found naturally in many eukaryotic cells and is essential for electron transport chain and energy generation in mitochondria. D-Panthenyl triacetate (PTA is an oil-soluble derivative of D-panthenol, which is essential for coenzyme A synthesis in the epithelium. Liposomal formulations that encapsulate both ingredients were prepared and optimized by applying response surface methodology for increased stability and skin penetration. The optimum formulation comprised 4.17 mg CoQ10, 4.22 mg PTA and 13.95 mg cholesterol per 100 mg of soy phosphatidylcholine. The encapsulation efficiency of the optimized formulation for CoQ10 and PTA was found to be 90.89%±3.61% and 87.84%±4.61%, respectively. Narrow size distribution was achieved with an average size of 161.6±3.6 nm, while a spherical and uniform shape was confirmed via scanning electron microscopy and transmission electron microscopy images. Cumulative release of 90.93% for PTA and 24.41% for CoQ10 was achieved after 24 hours of in vitro release study in sink conditions. Physical stability tests indicated that the optimized liposomes were suitable for storage at 4°C for at least 60 days. The results suggest that the optimized liposomal formulation would be a promising delivery system for both ingredients in various topical applications. Keywords: coenzyme Q10, D-panthenyl triacetate, liposomes, response surface methodology, stability

Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats

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OA, Andreassen; Weber, Christine; HA, Jorgensen

1999-01-01

dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL...

Kaempferol increases levels of coenzyme Q in kidney cells and serves as a biosynthetic ring precursor.

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Fernández-Del-Río, Lucía; Nag, Anish; Gutiérrez Casado, Elena; Ariza, Julia; Awad, Agape M; Joseph, Akil I; Kwon, Ohyun; Verdin, Eric; de Cabo, Rafael; Schneider, Claus; Torres, Jorge Z; Burón, María I; Clarke, Catherine F; Villalba, José M

2017-09-01

Coenzyme Q (Q) is a lipid-soluble antioxidant essential in cellular physiology. Patients with Q deficiencies, with few exceptions, seldom respond to treatment. Current therapies rely on dietary supplementation with Q 10 , but due to its highly lipophilic nature, Q 10 is difficult to absorb by tissues and cells. Plant polyphenols, present in the human diet, are redox active and modulate numerous cellular pathways. In the present study, we tested whether treatment with polyphenols affected the content or biosynthesis of Q. Mouse kidney proximal tubule epithelial (Tkpts) cells and human embryonic kidney cells 293 (HEK 293) were treated with several types of polyphenols, and kaempferol produced the largest increase in Q levels. Experiments with stable isotope 13 C-labeled kaempferol demonstrated a previously unrecognized role of kaempferol as an aromatic ring precursor in Q biosynthesis. Investigations of the structure-function relationship of related flavonols showed the importance of two hydroxyl groups, located at C3 of the C ring and C4' of the B ring, both present in kaempferol, as important determinants of kaempferol as a Q biosynthetic precursor. Concurrently, through a mechanism not related to the enhancement of Q biosynthesis, kaempferol also augmented mitochondrial localization of Sirt3. The role of kaempferol as a precursor that increases Q levels, combined with its ability to upregulate Sirt3, identify kaempferol as a potential candidate in the design of interventions aimed on increasing endogenous Q biosynthesis, particularly in kidney. Copyright © 2017 Elsevier Inc. All rights reserved.

Micronutrient special issue: Coenzyme Q{sub 10} requirements for DNA damage prevention

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Schmelzer, Constance, E-mail: schmelzer@fbn-dummerstorf.de [Leibniz Institute for Farm Animal Biology (FBN), Nutritional Physiology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf (Germany); Doering, Frank [University of Kiel, Institute of Human Nutrition and Food Science, Molecular Prevention, Heinrich-Hecht-Platz 10, 24118 Kiel (Germany)

2012-05-01

Coenzyme Q{sub 10} (CoQ{sub 10}) is an essential component for electron transport in the mitochondrial respiratory chain and serves as cofactor in several biological processes. The reduced form of CoQ{sub 10} (ubiquinol, Q{sub 10}H{sub 2}) is an effective antioxidant in biological membranes. During the last years, particular interest has been grown on molecular effects of CoQ{sub 10} supplementation on mechanisms related to DNA damage prevention. This review describes recent advances in our understanding about the impact of CoQ{sub 10} on genomic stability in cells, animals and humans. With regard to several in vitro and in vivo studies, CoQ{sub 10} provides protective effects on several markers of oxidative DNA damage and genomic stability. In comparison to the number of studies reporting preventive effects of CoQ{sub 10} on oxidative stress biomarkers, CoQ{sub 10} intervention studies in humans with a direct focus on markers of DNA damage are limited. Thus, more well-designed studies in healthy and disease populations with long-term follow up results are needed to substantiate the reported beneficial effects of CoQ{sub 10} on prevention of DNA damage.

Lithium carbonate and coenzyme Q10 reduce cell death in a cell model of Machado-Joseph disease

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C.M. Lopes-Ramos

Full Text Available Machado-Joseph disease (MJD or spinocerebellar ataxia type 3 (SCA3 is an autosomal dominant neurodegenerative disorder caused by expansion of the polyglutamine domain of the ataxin-3 (ATX3 protein. MJD/SCA3 is the most frequent autosomal dominant ataxia in many countries. The mechanism underlying MJD/SCA3 is thought to be mainly related to protein misfolding and aggregation leading to neuronal dysfunction followed by cell death. Currently, there are no effective treatments for patients with MJD/SCA3. Here, we report on the potential use of lithium carbonate and coenzyme Q10 to reduce cell death caused by the expanded ATX3 in cell culture. Cell viability and apoptosis were evaluated by MTT assay and by flow cytometry after staining with annexin V-FITC/propidium iodide. Treatment with lithium carbonate and coenzyme Q10 led to a significant increase in viability of cells expressing expanded ATX3 (Q84. In addition, we found that the increase in cell viability resulted from a significant reduction in the proportion of apoptotic cells. Furthermore, there was a significant change in the expanded ATX3 monomer/aggregate ratio after lithium carbonate and coenzyme Q10 treatment, with an increase in the monomer fraction and decrease in aggregates. The safety and tolerance of both drugs are well established; thus, our results indicate that lithium carbonate and coenzyme Q10 are good candidates for further in vivo therapeutic trials.

Serum Levels of Coenzyme Q10 in Patients with Multiple System Atrophy.

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Takashi Kasai

Full Text Available The COQ2 gene encodes an essential enzyme for biogenesis, coenzyme Q10 (CoQ10. Recessive mutations in this gene have recently been identified in families with multiple system atrophy (MSA. Moreover, specific heterozygous variants in the COQ2 gene have also been reported to confer susceptibility to sporadic MSA in Japanese cohorts. These findings have suggested the potential usefulness of CoQ10 as a blood-based biomarker for diagnosing MSA. This study measured serum levels of CoQ10 in 18 patients with MSA, 20 patients with Parkinson's disease and 18 control participants. Although differences in total CoQ10 (i.e., total levels of serum CoQ10 and its reduced form among the three groups were not significant, total CoQ10 level corrected by serum cholesterol was significantly lower in the MSA group than in the Control group. Our findings suggest that serum CoQ10 can be used as a biomarker in the diagnosis of MSA and to provide supportive evidence for the hypothesis that decreased levels of CoQ10 in brain tissue lead to an increased risk of MSA.

Bioavailability enhancement of coenzyme Q10: an extensive review of patents.

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Beg, Sarwar; Javed, Shamama; Kohli, Kanchan

2010-11-01

Coenzyme Q10 (CoQ10) is a major antioxidant principle found in human body which plays a vital role in maintaining several biochemical pathways of body. It acts as a potential mediator in transferring electrons in oxidoreductive reactions of electron transport chain. Chemically, it is a basic quinone containing moiety having a large and high molecular weight structure. Deficiency of this in body leads to several potential disorders like dysfunctions in cellular energetics, neurological degeneration, higher oxidative stress induced damage, breast cancer etc. The high molecular weight and lipophilicity of CoQ10 makes it poorly water soluble and consequently leads to low systemic availability. Several advancements have been made to enhance the bioavailability of CoQ10 using various approaches like size reduction, solubility enhancement (by solid dispersion, prodrug, complexation, ionization) and use of novel drug carriers such as liposomes, microspheres, nanoparticles, nanoemulsions and self-emulsifying system. The primary objective of the present review is to assemble patents representing the various approaches used for enhancement of CoQ10 bioavailability.

Effect of Coenzyme-Q10 on Doxorubicin-Induced Nephrotoxicity in Rats

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Azza A. K. El-Sheikh

2012-01-01

Full Text Available Nephrotoxicity is one of the limiting factors for using doxorubicin (Dox as an anticancer chemotherapeutic. Here, we investigated possible protective effect of coenzyme-Q10 (CoQ10 on Dox-induced nephrotoxicity and the mechanisms involved. Two doses (10 and 100 mg/kg of CoQ10 were administered orally to rats for 8 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of Dox (15 mg/kg at day 4 of the experiment. Our results showed that the low dose of CoQ10 succeeded in reversing Dox-induced nephrotoxicity to control levels (e.g., levels of blood urea nitrogen and serum creatinine, concentrations of renal reduced glutathione (GSH and malondialdehyde, catalase activity and caspase 3 expression, and renal histopathology. Alternatively, the high dose of CoQ10 showed no superior nephroprotection over the low dose, as there were no significant improvements in renal histopathology, catalase activity, or caspase 3 expression compared to the Dox-treated group. Interestingly, the high dose of CoQ10 alone significantly decreased renal GSH level as well as catalase activity and caused a mild induction of caspase 3 expression compared to control, probably due to a prooxidant effect at this dose of CoQ10. We conclude that CoQ10 protects from Dox-induced nephrotoxicity with a precaution to dosage adjustment.

Alcohol depletes coenzyme-Q10 associated with increased TNF-alpha secretion to induce cytotoxicity in HepG2 cells

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Vidyashankar, Satyakumar; Nandakumar, Krishna S.; Patki, Pralhad S.

2012-01-01

Highlights: ► Ethanol induced cytotoxicity in HepG2 cells in absence of lipogenesis. ► Ethanol inhibited HMG-CoA reductase activity. ► Ethanol induced HMG-CoA reductase inhibition is due to decreased cell viability. ► Incubation with mevalonate could not increase the cholesterol. ► Cytotoxicity brought about by CoQ10 depletion and increased TNF-alpha. -- Abstract: Alcohol consumption has been implicated to cause severe hepatic steatosis which is mediated by alcohol dehydrogenase (ADH) activity and CYP 450 2E1 expression. In this context, the effect of ethanol was studied for its influence on lipogenesis in HepG2 cell which is deficient of ADH and does not express CYP 450 2E1. The results showed that ethanol at 100 mM concentration caused 40% cytotoxicity at 72 h as determined by MTT assay. The incorporation of labeled [2- 14 C] acetate into triacylglycerol and phospholipid was increased by 40% and 26% respectively upon 24 h incubation, whereas incorporation of labeled [2- 14 C] acetate into cholesterol was not significantly increased. Further, ethanol inhibited HMG-CoA reductase which is a rate-limiting enzyme in the cholesterol biosynthesis. It was observed that, HMG-CoA reductase inhibition was brought about by ethanol as a consequence of decreased cell viability, since incubation of HepG2 cells with mevalonate could not increase the cholesterol content and increase the cell viability. Addition of ethanol significantly increased TNF-alpha secretion and depleted mitochondrial coenzyme-Q 10 which is detrimental for cell viability. But vitamin E (10 mM) could partially restore coenzyme-Q 10 and glutathione content with decreased TNF-alpha secretion in ethanol treated cells. Further, lipid peroxidation, glutathione peroxidase and superoxide dismutase enzyme activities remained unaffected. Ethanol decreased glutathione content while, GSH/GSSG ratio was significantly higher compared to other groups showing cellular pro-oxidant and antioxidant balance remained

Activity of coenzyme Q 10 (Q-Ter multicomposite) on recovery time in noise-induced hearing loss.

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Staffa, Paola; Cambi, Jacopo; Mezzedimi, Chiara; Passali, Desiderio; Bellussi, Luisa

2014-01-01

A potential consequence of exposure to noise is a temporary reduction in auditory sensitivity known as temporary threshold shift (TTS), which mainly depends on the intensity and duration of exposure to the noise. Recovery time is related to the amount of initial hearing loss, and the most recovery takes place during the first 15 min following exposure. This study evaluated the efficacy in otoprotection against noise-induced hearing loss of an orally administrated food supplement containing coenzyme Q 10 -Ter. This water-soluble formulation of coenzyme Q 10 shows better bioavailability than the native form and has been found to have a protective effect on outer hair cells after exposure to noise in animal models. Thirty volunteers were enrolled, and the right ear of each subject was exposed to a narrow-band noise centered at 3 kHz for 10 min at the intensity of 90 dB HL. In the 30 subjects enrolled, TTS was evaluated after 2, 15, and 30 min and the recovery time was recorded in each subject. The longest recovery time was 45 min. Among the 18 subjects who underwent a second test after treatment with Q-Ter, the mean recovery time was 31.43 min. The results of the present study show that 30 days' treatment with Q-Ter can aid faster recovery after exposure to noise (P < 0.0001). The reduction in the recovery time following treatment can be explained by Q-Ter-mediated improvement of the outer hair cells' response to oxidative stress.

A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

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Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

2015-02-01

Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) (p pain severity and interference scores increased with simvastatin therapy (both p muscle strength or VO2max with simvastatin with or without CoQ10 (all p > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups (p = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial RegistrationNCT01140308; www.clinicaltrials.gov. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The use of coenzyme Q0 as a template in the development of a molecularly imprinted polymer for the selective recognition of coenzyme Q10.

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Contin, Mario; Flor, Sabrina; Martinefski, Manuela; Lucangioli, Silvia; Tripodi, Valeria

2014-01-07

In this work, a novel molecularly imprinted polymer (MIP) for use as a solid phase extraction sorbent was developed for the determination of coenzyme Q10 (CoQ10) in liver extract. CoQ10 is an essential cofactor in mitochondrial oxidative phosphorylation and a powerful antioxidant agent found in low concentrations in biological samples. This fact and its high hydrophobicity make the analysis of CoQ10 technically challenging. Accordingly, a MIP was synthesised using coenzyme Q0 as the template, methacrylic acid as the functional monomer, acetonitrile as the porogen, ethylene glycol dimethacrylate as the crosslinker and benzoyl peroxide as the initiator. Various parameters affecting the polymer preparation and extraction efficiency were evaluated. Morphological characterisation of the MIP and its proper comparison with C18 as a sorbent in solid phase extraction were performed. The optimal conditions for the molecularly imprinted solid phase extraction (MISPE) consisted of 400 μL of sample mixed with 30 mg of MIP and 600 μL of water to reach the optimum solution loading. The loading was followed by a washing step consisting of 1 mL of a 1-propanol solution (1-propanol:water, 30:70,v/v) and elution with 1 mL of 1-propanol. After clean-up, the CoQ10 in the samples was analysed by high performance liquid chromatography. The extraction recoveries were higher than 73.7% with good precision (3.6-8.3%). The limits of detection and quantification were 2.4 and 7.5 μg g(-1), respectively, and a linear range between 7.5 and 150 μg g(-1) of tissue was achieved. The new MISPE procedure provided a successful clean-up for the determination of CoQ10 in a complex matrix. Copyright © 2013 Elsevier B.V. All rights reserved.

Preformed β-amyloid fibrils are destabilized by coenzyme Q10 in vitro

International Nuclear Information System (INIS)

Ono, Kenjiro; Hasegawa, Kazuhiro; Naiki, Hironobu; Yamada, Masahito

2005-01-01

Inhibition of the formation of β-amyloid fibrils (fAβ), as well as the destabilization of preformed fAβ in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA) and wine-related polyphenol, myricetin (Myr), inhibit fAβ formation from Aβ and destabilize preformed fAβ in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of coenzyme Q 10 (CoQ 10 ) on the formation, extension, and destabilization of fAβ at pH 7.5 at 37 deg C in vitro. We next compared the anti-amyloidogenic activities of CoQ 10 with NDGA and Myr. CoQ 10 dose-dependently inhibited fAβ formation from amyloid β-peptide (Aβ), as well as their extension. Moreover, it destabilized preformed fAβs. The anti-amyloidogenic effects of CoQ 10 were slightly weaker than those of NDGA and Myr. CoQ 10 could be a key molecule for the development of therapeutics for AD

Beneficial Effects of Coenzyme Q10 in Reduction of Testicular Tissue Alteration Following Induction of Diabetes in Adult Rats

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Kianifard Davoud

2015-03-01

Full Text Available Background and Aims: Various types of infertility are associated with uncontrolled hyperglycemia and diabetes. Development of oxidative stress is one the most important factors in the alteration of spermatogenesis in diabetic conditions. Consequently, the reduction of oxidative stress with antioxidant compounds can be effective in the reduction of tissue alterations. The aim of this study was to evaluate the efficacy of coenzyme Q10 in improvement of spermatogenesis in adult diabetic rats. Material and Methods: 32 adult rats were divided into four groups of control and treatment. Coenzyme Q10 (10 mg/kg body weight - b.w. was administrated to one control and one diabetic (intraperitoneal injection of 45 mg/kg b.w. of Streptozotocin groups. Blood concentrations of FSH, LH and Testosterone were measured. Histology of testicular tissue and sperm analysis were considered for evaluation of spermatogenesis. Results: Administration of Coenzyme Q10 led to increase of pituitary gonadotropins levels in diabetic rats. Testosterone levels were not changed significantly. Testicular morphology, spermatogenic indices and sperm analysis were improved in treated diabetic rats. Conclusions: The results of this study suggest that the use of Coenzyme Q10 has positive effects in reduction of spermatogenic alterations following induction of experimental diabetes in rats.

Effects of Oral, Vaginal, and Transdermal Hormonal Contraception on Serum Levels of Coenzyme Q10, Vitamin E, and Total Antioxidant Activity

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Prabhudas R. Palan

2010-01-01

coenzyme Q10 levels compared with normal subjects. Serum TAOC levels were significantly lower (P<.05 among the contraceptive user groups. Alterations in coenzyme Q10 and α-tocopherol induced by hormonal contraception and the potential effect(s of exogenous ovarian hormones should be taken into consideration in future antioxidant research.

Novel Lipid-Free Nanoformulation for Improving Oral Bioavailability of Coenzyme Q10

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Huafeng Zhou

2014-01-01

Full Text Available To improve the bioavailability of orally administered lipophilic coenzyme Q10 (CoQ10, we formulated a novel lipid-free nano-CoQ10 system stabilized by various surfactants. Nano-CoQ10s, composed of 2.5% (w/w CoQ10, 1.67% (w/w surfactant, and 41.67% (w/w glycerol, were prepared by hot high-pressure homogenization. The resulting formulations were characterized by particle size, zeta potential, differential scanning calorimetry, and cryogenic transmission electron microscopy. We found that the mean particle size of all nano-CoQ10s ranged from 66.3±1.5 nm to 92.7±1.5 nm and the zeta potential ranged from -12.8±1.4 mV to -41.6±1.4 mV. The CoQ10 in nano-CoQ10s likely existed in a supercooled state, and nano-CoQ10s stored in a brown sealed bottle were stable for 180 days at 25°C. The bioavailability of CoQ10 was evaluated following oral administration of CoQ10 formulations in Sprague-Dawley rats. Compared to the values observed following administration of CoQ10-Suspension, nano-CoQ10 modified with various surfactants significantly increased the maximum plasma concentration and the area under the plasma concentration-time curve. Thus, the lipid-free system of a nano-CoQ10 stabilized with a surfactant may be an effective vehicle for improving oral bioavailability of CoQ10.

Coenzyme Q10 Supplementation Modulates NFκB and Nrf2 Pathways in Exercise Training

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Ragip Pala, Cemal Orhan, Mehmet Tuzcu, Nurhan Sahin, Shakir Ali, Vedat Cinar, Mustafa Atalay, Kazim Sahin

2016-03-01

Full Text Available This study reports the effects of Q10, coenzyme Q10 or ubiquinone, a component of the electron transport chain in mitochondria, on nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB, inhibitors of kappa B (IκB, nuclear factor (erythroid-derived 2-like 2 (Nrf2 and hemeoxygenase 1 (HO-1 in rats after chronic exercise training for 6 weeks. 8-week old male Wistar rats were assigned randomly to one of four treatments planned in a 2 x 2 factorial arrangement of two condition (sedentary vs. exercise training, and two coenzyme Q10 levels (0 and 300 mg/kg per day for 6 weeks. The expression levels of the target proteins were determined in the heart, liver and muscle, and biochemical parameters including creatinine, urea, glucose and lipid profile were investigated in plasma. When compared with sedentary group, significant decreases in heart, liver and muscle NFκB levels by 45%, 26% and 44% were observed in Q10 supplemented rats after exercise training, respectively, while the inhibitory protein IκB increased by 179%, 111% and 127% in heart, liver and muscle tissues. Q10 supplementation caused an increase in Nrf2 (167%, 165% and 90% and HO-1 (107%, 156% and 114% after exercise training in heart, liver and muscle tissues (p < 0.05. No significant change was observed in any of the parameters associated with protein, carbohydrate and lipid metabolism, except that exercise caused a decrease in plasma triglyceride, which was further decreased by Q10. In conclusion, these results suggest that Q10 modulates the expression of NFκB, IκB, Nrf2 and HO-1 in exercise training, indicating an anti-inflammatory effect of Q10 and emphasizes its role in antioxidant defense.

Reversal of statin-induced memory dysfunction by co-enzyme Q10: a case report

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Okeahialam BN

2015-11-01

Full Text Available Basil N Okeahialam Cardiology Sub-Unit 1, Department of Medicine, Jos University Teaching Hospital, Jos, Nigeria Abstract: Statins are useful in the armamentarium of the clinician dealing with dyslipidemia, which increases cardiovascular morbi-mortality in hypertensive and diabetic patients among others. Dyslipidemia commonly exists as a comorbidity factor in the development of atherosclerotic cardiovascular disease. Use of statins is however associated with side effects which at times are so disabling as to interfere with activities of daily living. There are various ways of dealing with this, including use of more water-soluble varieties, intermittent dosing, or use of statin alternatives. Of late, use of co-enzyme Q10 has become acceptable for the muscle side effects. Only one report of any benefit on the rarely reported memory side effect was encountered by the author in the search of English medical literature. This is a report of a documented case of a Nigerian woman with history of statin intolerance in this case, memory dysfunction despite persisting dyslipidemia comorbidity. Her memory dysfunction side effect which interfered with activities of daily living and background muscle pain cleared when coenzyme Q10 was administered alongside low dose statin. Her lipid profile normalized and has remained normal. It is being recommended for use when statin side effects (muscle- and memory-related impair quality of life and leave patient at dyslipidemia-induced cardiovascular morbi-mortality. Keywords: statin, memory dysfunction, co-enzyme Q10, improvement

Comparision of Inhibitory effects of Satureja Khozistanica,vitamin E and coenzyme Q10 on LDL peroxidation induced-CuSO4 in vitro

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hasan Ahmadvand

2010-02-01

Full Text Available Oxidation of low-density lipoprotein (LDL has been strongly suggested as a key factor in the pathogenesis of atherosclerosis. Thus the inclusion of some anti-oxidant compounds such as Satureja Khozistanica,vitamin E and coenzyme Q10 in daily dietary food stuff may inhibit the production of oxidized LDL and may decrease both the development and the progression of atherosclerosis. The present study investigated the inhibitory effects of Satureja Khozistanica, vitamin E and coenzyme Q10 on LDL peroxidation induced by CuSO4 quantitatively in vitro. Materials and Methods: LDL was incubated with CuSO4 and the formation of conjugated dienes and thiobarbituric acid reactive substances (TBARS of LDL were monitored as markers of LDL oxidation. Inhibition of this Cu-induced oxidation was studied in the presence of extracts of Satureja Khozistanica,vitamin E and coenzyme Q10. Results: It was demonstrated that Satureja Khozistanica like vitamin E and coenzyme Q10 is able to inhibit LDL oxidation and decrease the resistance of LDL against oxidation in vitro. Conclusion: This study showed that Satureja Khozistanica similar to vitamin E and coenzyme Q10 prevented the oxidation of LDL in vitro and it may suggest that they have the similar effect in vivo

In vitro effects of zinc, D-aspartic acid, and coenzyme-Q10 on sperm function.

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Giacone, Filippo; Condorelli, Rosita A; Mongioì, Laura M; Bullara, Valentina; La Vignera, Sandro; Calogero, Aldo E

2017-05-01

Reactive oxygen species favor reproductive processes at low concentrations, but damage spermatozoa and decrease their fertilizing capacity at high concentrations. During infection and/or inflammation of the accessory sex glands reactive oxygen species overproduction may occur which, in turn, may negatively impact on sperm motility, sperm DNA fragmentation, and lipid peroxidation. A number of nutraceutical formulations containing antioxidant molecules have been developed to counteract the deleterious effects of the oxidative stress. A recent formulation containing zinc, D-aspartic acid, and coenzyme-Q10 is present in the pharmaceutical market. Based on these premises, the aim of the present study was to evaluate the effects of this combination on spermatozoa in vitro. The study was conducted on 24 men (32.2 ± 5.5 years): 12 normozoospermic men and 12 asthenozoospermic patients. Spermatozoa from each sample were divided into two control aliquots (aliquot A and B) and an aliquot incubated with zinc, D-aspartic acid, and coenzyme-Q10 (aliquot C). After 3 h of incubation, the following parameters were evaluated: progressive motility, number of spermatozoa with progressive motility recovered after swim-up, lipid peroxidation, and DNA fragmentation. Incubation with zinc, D-aspartic acid, and coenzyme-Q10 maintained sperm motility in normozoospermic men (37.7 ± 1.2 % vs. 35.8 ± 2.3 % at time zero) and improved it significantly in asthenozoospermic patients (26.5 ± 1.9 % vs. 18.8 ± 2.0 % at time zero) (p aspartic acid, and coenzyme-Q10 (p < 0.05) in both normozospermic men (1.0 ± 0.4 % vs. 2.4 ± 0.9 %) and asthenozooseprmic patients (0.2 ± 0.1 % vs. 0.6 ± 0.2 %). No statistically significant effect was observed on sperm DNA fragmentation. This nutraceutical formulation may be indicated in vitro during the separation of the spermatozoa in the assisted reproduction techniques, during which the spermatozoa

Rosuvastatin lowers coenzyme Q10 levels, but not mitochondrial adenosine triphosphate synthesis, in children with familial hypercholesterolemia

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Avis, Hans J.; Hargreaves, Ian P.; Ruiter, Jos P. N.; Land, John M.; Wanders, Ronald J.; Wijburg, Frits A.

2011-01-01

To investigate whether statin therapy affects coenzyme Q10 (CoQ10) status in children with heterozygous familial hypercholesterolemia (FH). Samples were obtained at baseline (treatment naïve) and after dose titration with rosuvastatin, aiming for a low-density lipoprotein cholesterol level of 110

Modeling of process parameters for enhanced production of coenzyme Q10 from Rhodotorula glutinis.

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Balakumaran, Palanisamy Athiyaman; Meenakshisundaram, Sankaranarayanan

2015-01-01

Coenzyme Q10 (CoQ10) plays an indispensable role in ATP generation through oxidative phosphorylation and helps in scavenging superoxides generated during electron transfer reactions. It finds extensive applications specifically related to oxidative damage and metabolic dysfunctions. This article reports the use of a statistical approach to optimize the concentration of key variables for the enhanced production of CoQ10 by Rhodotorula glutinis in a lab-scale fermenter. The culture conditions that promote optimum growth and CoQ10 production were optimized and the interaction of significant variables para-hydroxybenzoic acid (PHB, 819.34 mg/L) and soybean oil (7.78% [v/v]) was studied using response surface methodology (RSM). CoQ10 production increased considerably from 10 mg/L (in control) to 39.2 mg/L in batch mode with RSM-optimized precursor concentration. In the fed-batch mode, PHB and soybean oil feeding strategy enhanced CoQ10 production to 78.2 mg/L.

Characterisation and Skin Distribution of Lecithin-Based Coenzyme Q10-Loaded Lipid Nanocapsules

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Zhou, Huafeng; Yue, Yang; Liu, Guanlan; Li, Yan; Zhang, Jing; Yan, Zemin; Duan, Mingxing

2010-10-01

The purpose of this study was to investigate the influence of the inner lipid ratio on the physicochemical properties and skin targeting of surfactant-free lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs). The smaller particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of CoQ10/GTCC (Caprylic/capric triglyceride); however, the zeta potential of CoQ10-LNCs was above /- 60 mV/ with no distinct difference among them at different ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm, as verified by differential scanning calorimetry (DSC) in one heating-cooling cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by cryogenic transmission electron microscopy (Cryo-TEM). The skin penetration results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial dermal targeting were achieved by the CoQ10-LNCs application. The highest fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These observations suggest that lecithin-based LNCs could be used as a promising topical delivery vehicle for lipophilic compounds.

Characterisation and Skin Distribution of Lecithin-Based Coenzyme Q10-Loaded Lipid Nanocapsules

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Yan Zemin

2010-01-01

Full Text Available Abstract The purpose of this study was to investigate the influence of the inner lipid ratio on the physicochemical properties and skin targeting of surfactant-free lecithin-based coenzyme Q10-loaded lipid nanocapsules (CoQ10-LNCs. The smaller particle size of CoQ10-LNCs was achieved by high pressure and a lower ratio of CoQ10/GTCC (Caprylic/capric triglyceride; however, the zeta potential of CoQ10-LNCs was above /− 60 mV/ with no distinct difference among them at different ratios of CoQ10/GTCC. Both the crystallisation point and the index decreased with the decreasing ratio of CoQ10/GTCC and smaller particle size; interestingly, the supercooled state of CoQ10-LNCs was observed at particle size below about 200 nm, as verified by differential scanning calorimetry (DSC in one heating–cooling cycle. The lecithin monolayer sphere structure of CoQ10-LNCs was investigated by cryogenic transmission electron microscopy (Cryo-TEM. The skin penetration results revealed that the distribution of Nile red-loaded CoQ10-LNCs depended on the ratio of inner CoQ10/GTCC; moreover, epidermal targeting and superficial dermal targeting were achieved by the CoQ10-LNCs application. The highest fluorescence response was observed at a ratio of inner CoQ10/GTCC of 1:1. These observations suggest that lecithin-based LNCs could be used as a promising topical delivery vehicle for lipophilic compounds.

Coenzyme Q10 production in plants: current status and future prospects.

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Parmar, Sanjay Singh; Jaiwal, Anjali; Dhankher, Om Parkash; Jaiwal, Pawan K

2015-06-01

Coenzyme Q10 (CoQ10) or Ubiquinone10 (UQ10), an isoprenylated benzoquinone, is well-known for its role as an electron carrier in aerobic respiration. It is a sole representative of lipid soluble antioxidant that is synthesized in our body. In recent years, it has been found to be associated with a range of patho-physiological conditions and its oral administration has also reported to be of therapeutic value in a wide spectrum of chronic diseases. Additionally, as an antioxidant, it has been widely used as an ingredient in dietary supplements, neutraceuticals, and functional foods as well as in anti-aging creams. Since its limited dietary uptake and decrease in its endogenous synthesis in the body with age and under various diseases states warrants its adequate supply from an external source. To meet its growing demand for pharmaceutical, cosmetic and food industries, there is a great interest in the commercial production of CoQ10. Various synthetic and fermentation of microbial natural producers and their mutated strains have been developed for its commercial production. Although, microbial production is the major industrial source of CoQ10 but due to low yield and high production cost, other cost-effective and alternative sources need to be explored. Plants, being photosynthetic, producing high biomass and the engineering of pathways for producing CoQ10 directly in food crops will eliminate the additional step for purification and thus could be used as an ideal and cost-effective alternative to chemical synthesis and microbial production of CoQ10. A better understanding of CoQ10 biosynthetic enzymes and their regulation in model systems like E. coli and yeast has led to the use of metabolic engineering to enhance CoQ10 production not only in microbes but also in plants. The plant-based CoQ10 production has emerged as a cost-effective and environment-friendly approach capable of supplying CoQ10 in ample amounts. The current strategies, progress and constraints of

Water-soluble coenzyme Q10 formulation in presbycusis: long-term effects.

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Guastini, Luca; Mora, Renzo; Dellepiane, Massimo; Santomauro, Valentina; Giorgio, Manini; Salami, Angelo

2011-05-01

These findings provide the basis for understanding the duration of the effect after the last use of the drug and encourage a larger clinical trial to collect additional evidence on the effect of coenzyme Q10 (CoQ10) in preventing the development of hearing loss in subjects with presbycusis. The aim of this study was to evaluate the long-term effects of a water-soluble formulation of CoQ10 (Q-TER) in subjects with presbycusis. Sixty patients with presbycusis were included and divided at random into three numerically equal groups. For 30 days, group A underwent therapy with Q-TER, group B underwent therapy with vitamin E, and group C received placebo. Before, at the end, and 6 months after the end of the treatment, all patients underwent evaluation of pure tone audiometry, transient evoked otoacoustic emissions and otoacoustic products of distortion, auditory brainstem response, and speech audiometry. Compared with group B, at the end of the treatment in group A the pure tone audiometry showed a significant (p < 0.05) improvement of the audiometric thresholds at 1000, 2000, 4000, and 8000 Hz. This improvement was confirmed by the speech audiometry and last check. We found no significant differences in the other parameters and in group C.

The effect of coenzyme Q10 in statin myopathy.

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Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

2012-01-01

Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (pmuscle weakness by 44.4% (pmuscle pain and sensitivity statistically significantly decreased.

Acute Hypoglycemia Induces Painful Neuropathy and the Treatment of Coenzyme Q10

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Yan Ping Zhang

2016-01-01

Full Text Available Diabetic neuropathic pain is reduced with tight glycemic control. However, strict control increases the risk of hypoglycemic episodes, which are themselves linked to painful neuropathy. This study explored the effects of hypoglycemia-related painful neuropathy. Pretreatment with coenzyme Q10 (CoQ10 was performed to explore the preventive effect of CoQ10 on hypoglycemia-related acute neuropathic pain. Two strains of mice were used and 1 unit/kg of insulin was given to induce hypoglycemia. Mechanical sensitivity of hindpaw withdrawal thresholds was measured using von Frey filaments. Blood glucose levels were clamped at normal levels by joint insulin and glucose injection to test whether insulin itself induced hypersensitivity. Results suggest that the increased mechanical sensitivity after insulin injection is related to decreased blood glucose levels. When blood glucose levels remained at a normal level by the linked administration of insulin and glucose, mice demonstrated no significant change in mechanical sensitivity. Pretreatment with CoQ10 prevented neuropathic pain and the expression of the stress factor c-Fos. These results support the concept that pain in the diabetic scenario can be the result of hypoglycemia and not insulin itself. Additionally, pretreatment with CoQ10 may be a potent preventive method for the development of neuropathic pain.

Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: A possible role in statin-induced hepatotoxicity?

International Nuclear Information System (INIS)

Tavintharan, S.; Ong, C.N.; Jeyaseelan, K.; Sivakumar, M.; Lim, S.C.; Sum, C.F.

2007-01-01

Lowering of low-density lipoprotein cholesterol is well achieved by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). Statins inhibit the conversion of HMG-CoA to mevalonate, a precursor for cholesterol and coenzyme Q10 (CoQ 10 ). In HepG2 cells, simvastatin decreased mitochondrial CoQ 10 levels, and at higher concentrations was associated with a moderately higher degree of cell death, increased DNA oxidative damage and a reduction in ATP synthesis. Supplementation of CoQ 10 , reduced cell death and DNA oxidative stress, and increased ATP synthesis. It is suggested that CoQ 10 deficiency plays an important role in statin-induced hepatopathy, and that CoQ 10 supplementation protects HepG2 cells from this complication

Promotion of growth by Coenzyme Q10 is linked to gene expression in C. elegans.

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Fischer, Alexandra; Niklowitz, Petra; Menke, Thomas; Döring, Frank

2014-10-03

Coenzyme Q (CoQ, ubiquinone) is an essential component of the respiratory chain, a cofactor of pyrimidine biosynthesis and acts as an antioxidant in extra mitochondrial membranes. More recently CoQ has been identified as a modulator of apoptosis, inflammation and gene expression. CoQ deficient Caenorhabditis elegans clk-1 mutants show several phenotypes including a delayed postembryonic growth. Using wild type and two clk-1 mutants, here we established an experimental set-up to study the consequences of endogenous CoQ deficiency or exogenous CoQ supply on gene expression and growth. We found that a deficiency of endogenous CoQ synthesis down-regulates a cluster of genes that are important for growth (i.e., RNA polymerase II, eukaryotic initiation factor) and up-regulates oxidation reactions (i.e., cytochrome P450, superoxide dismutase) and protein interactions (i.e., F-Box proteins). Exogenous CoQ supply partially restores the expression of these genes as well as the growth retardation of CoQ deficient clk-1 mutants. On the other hand exogenous CoQ supply does not alter the expression of a further sub-set of genes. These genes are involved in metabolism (i.e., succinate dehydrogenase complex), cell signalling or synthesis of lectins. Thus, our work provides a comprehensive overview of genes which can be modulated in their expression by endogenous or exogenous CoQ. As growth retardation in CoQ deficiency is linked to the gene expression profile we suggest that CoQ promotes growth via gene expression. Copyright © 2014 Elsevier Inc. All rights reserved.

Cold-Induced Ascites in Broilers: Effects of Vitamin C and Coenzyme Q10

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MH Nemati

Full Text Available ABSTRACT We hypothesized that the supplementation of vitamin C (Vit. C and coenzyme Q10 (CoQ10 alone or in combination could reduce the negative effects of cold stress in broilers. Four hundred male chicks were exposed for 24 h to cold stress (15 ºC starting from 15d of age, while a positive control group (PC, 100 birds was kept under normal temperature condition. The experimental groups under cold stress (four treatments in 5 replicates of 20 birds were: negative control (NC, basal diet, Vit. C (basal diet + 300 mg/kg Vit. C, CoQ10 (basal diet + 40 mg/kg CoQ10 and Vit. C plus CoQ10 (basal diet + Vit. C+ CoQ10at above mentioned doses. Vit. C or CoQ10 supplementation were restored (p<0.01 performance and lowered (p<0.01 ascites mortality. Blood hematocrit and hemoglobin concentration were decreased (p<0.01 to the level comparable to PC by Vit. C supplementation. Lower plasma concentrations of thyroxin (T4 and higher triiodothyronine (T3 were observed in NC birds (p<0.01 and were not affected by Vit. C or CoQ10. In conclusion, supplementation of Vit. C or CoQ10 in diet of broilers under cold stress conditions resulted improved performance parameters (body weight and feed conversion ratio and ascites related traits (low red blood cell count, hematocrit, T3, and heart weights and high T4. No additional benefit was observed by combination of Vit. C and CoQ10.

Interaction of Coenzyme Q10 with Liposomes and its Impact on Suppression of Selenite – Induced Experimental Cataract

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Medhat Wahba Shafaa

2018-03-01

Full Text Available Purpose: To stress the influence of Coenzyme Q10 (CoQ10 on the structural properties of liposomes as model membranes and to investigate the possible role of CoQ10 or CoQ10 doped in liposomes when topically instilled as eye drops, in preventing cataract. Methods: The molecular interaction between liposomes and Coenzyme Q10 was examined using differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR. Rat pups were randomly divided into six groups comprising 15 pups. Group (1, control group. Group (2, untreated model of cataract, received a single subcutaneous injection of sodium selenite. Instillation of pure CoQ10 (Group 3, CoQ10 encapsulated into neutral (Group 4, positive (Group 5 and negative (Group 6 Dipalmitoyl phosphatidylcholine (DPPC liposomes on the opacification of lenses in rat pups after sodium selenite injection was topically received. Results: The incorporated CoQ10 is probably associated with lipid bilayers where it interacts to a large extent and perturbs them. This results in strong broadening and shift to lower temperature (94°C of the major characteristic endothermic peak of pure DPPC at 105°C. FTIR showed that the incorporation of CoQ10 into DPPC induces a conformational change in the polar region of DPPC. Ophthalmological and Biochemical studies revealed that CoQ10 alone followed by negatively charged liposomes doped with CoQ10 are more effective in reducing the progress of cataract as well as improving the lens soluble proteins levels and total antioxidant capacity. Conclusion: The interactions of CoQ10 with membrane systems may contribute to a better understanding of CoQ10 physiological properties and the development of therapeutically advanced systems.

The effect of long-term treatment with coenzyme Q10 on nucleic acid modifications by oxidation in children with Down syndrome

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Larsen, Emil List; Padella, Lucia; Bergholdt, Helle Kirstine Mørup

2018-01-01

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....

Nanoencapsulation of coenzyme Q10 and vitamin E acetate protects against UVB radiation-induced skin injury in mice.

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Pegoraro, Natháli S; Barbieri, Allanna V; Camponogara, Camila; Mattiazzi, Juliane; Brum, Evelyne S; Marchiori, Marila C L; Oliveira, Sara M; Cruz, Letícia

2017-02-01

This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

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Sun J

2012-11-01

Full Text Available Jiao Sun,1 Fan Wang,1,2 Yue Sui,1 Zhennan She,1 Wenjun Zhai,1 Chunling Wang,1 Yihui Deng11College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China; 2Beijing Zhijianjinrui Applied Pharmaceutical Science Inc, Beijing, ChinaAbstract: In this paper work, four naked nanocrystals (size range 80–700 nm were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.Keywords: particle size, solubility, dissolution, nanocrystal, bioavailability, coenzyme Q10

[Effect of phlebodium decumanum and coenzyme Q10 on sports performance in professional volleyball players].

Science.gov (United States)

García Verazaluce, Juan José; Vargas Corzo, María Del Carmen; Aguilar Cordero, María José; Ocaña Peinado, Francisco; Sarmiento Ramírez, Álvaro; Guisado Barrilao, Rafael

2014-10-03

Physical training programmes are based on provoking transitory states of fatigue in order to induce super compensation by the biological systems involved in the activity, in order to improve the athlete's medium-long term performance. The administration of nutritional supplements with antioxidant and immunomodulatory properties, such as Phlebodium decumanum and coenzyme Q10, can be a very advantageous means of achieving recovery from the inflammation and tissue damage caused by the stress of prolonged, intense exercise. An experimental, longitudinal, double- blind experiment was conducted, with three randomised groups obtained from a sample of 30 male volleyball players (aged 22-32 years) at the University of Granada, with a high level of training (17 hours a week during the 6 months preceding the study). The effects were then evaluated of a month-long physical training programme, common to all the study groups, associated with the simultaneous administration of the following nutritional supplements: Phlebodium decumanum (4 capsules of 400 mg/capsule, daily), Experimental Group 1; Phlebodium decumanum (same dose and schedule as Group 1) plus coenzyme Q10 (4 capsules of 30 mg/ capsule, daily), Experimental Group 2; a placebo substance, Control Group. The following dependent blood variables were examined to assess the effects of the intervention on the basal immune and endocrine-metabolic profile: cortisol and interleukin-6, both related to the axis of exercise-induced stress; and lactic acid and ammonium, related essentially to the anaerobic metabolism of energy. All the study groups presented favourable adaptive changes with respect to the endocrine-metabolic and immune profile, as reflected by a significant decrease in the post-test concentrations of cortisol, interleukin 6, lactic acid and ammonium, compared to the values recorded before the physical activity with/without nutritional supplement, per protocol. The groups that achieved the most favourable profile

Interaction of coenzyme Q10 with the intestinal drug transporter P-glycoprotein.

Science.gov (United States)

Itagaki, Shirou; Ochiai, Akiko; Kobayashi, Masaki; Sugawara, Mitsuru; Hirano, Takeshi; Iseki, Ken

2008-08-27

In clinical trials, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions can often directly affect the therapeutic safety and efficacy of many drugs. Oral delivery is the most desirable means of drug administration. Changes in the activity of drug transporters may substantially influence the absorption of administered drugs from the intestine. However, there have been a few studies on food-drug interactions involving transporters. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences. Coenzyme Q10 (CoQ10) is very widely consumed by humans as a food supplement because of its recognition by the public as an important nutrient in supporting human health. Since intestinal efflux transporter P-glycoprotein (P-gp) is one of the major factors in drug-drug interactions, we focused on this transporter. We report here for the first time that CoQ10, which is widely used as a food supplement, affects the transport activity of P-gp.

Water-soluble Coenzyme Q10 formulation (Q-ter) promotes outer hair cell survival in a guinea pig model of noise induced hearing loss (NIHL).

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Fetoni, Anna Rita; Piacentini, Roberto; Fiorita, Antonella; Paludetti, Gaetano; Troiani, Diana

2009-02-27

The mitochondrial respiratory chain is a powerful source of reactive oxygen species (ROS) also in noise induced hearing loss (NIHL) and anti-oxidants and free-radicals scavengers have been shown to attenuate the damage. Coenzyme Q(10) (CoQ(10)) or ubiquinone has a bioenergetic role as a component of the mithocondrial respiratory chain, it inhibits mitochondrial lipid peroxidation, inducing ATP production and it is involved in ROS removal and prevention of oxidative stress-induced apoptosis. However the therapeutic application of CoQ(10) is limited by the lack of solubility and poor bio- availability, therefore it is a challenge to improve its water solubility in order to ameliorate the efficacy in tissues and fluids. This study was conducted in a model of acoustic trauma in the guinea pig where the effectiveness of CoQ(10) was compared with a soluble formulation of CoQ(10) (multicomposite CoQ(10) Terclatrate, Q-ter) given intraperitoneally 1 h before and once daily for 3 days after pure tone noise exposure (6 kHz for 1 h at 120 dB SPL). Functional and morphological studies were carried out by measuring auditory brainstem responses, scanning electron microscopy for hair cell loss count, active caspase 3 staining and terminal deoxynucleotidyl transferase-mediated dUTP labelling assay in order to identify initial signs of apoptosis. Treatments decreased active caspase 3 expression and the number of apoptotic cells, but animals injected with Q-ter showed a greater degree of activity in preventing apoptosis and thus in improving hearing. These data confirm that solubility of Coenzyme Q(10) improves the ability of CoQ(10) in preventing oxidative injuries that result from mitochondrial dysfunction.

Coenzyme Q10 and pro-inflammatory markers in children with Down syndrome: clinical and biochemical aspects

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Moushira E. Zaki

2017-01-01

Conclusion: Interleukin 6 and tumor necrosis factor α levels in young children with Down syndrome may be used as biomarkers reflecting the neurodegenerative process in them. Coenzyme Q10 might have a role as a good supplement in young children with Down syndrome to ameliorate the neurological symptoms.

Effect of the additives on clouding behavior and thermodynamics of coenzyme Q10-Kolliphor HS15 micelle aqueous solutions

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Hu, Li; Zhang, Jing; Zhu, Chao; Pan, Hong-chun; Liu, Hong

2017-11-01

Herein we investigate the effect of different additives (electrolytes, amino acids, PEG, and sugars) on the cloud points (CP) of coenzyme Q10 (CoQ10) - Kolliphor HS15 (HS15) micelle aqueous solutions. The CP values were decreased with the increase of electrolytes and sugars, following: CPAl3+ reduced the CP. A depression of CP for CoQ10-HS15 micelle solution with PEG was molecular weight of PEG dependent. The significant thermodynamic parameters were also evaluated and discussed.

Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats.

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Yoneda, Toshiki; Tomofuji, Takaaki; Kawabata, Yuya; Ekuni, Daisuke; Azuma, Tetsuji; Kataoka, Kota; Kunitomo, Muneyoshi; Morita, Manabu

2014-12-10

Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10), may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old) (n = 27) received topical application of ointment containing 5% rCoQ10 (experimental group) or control ointment (control group) to the sockets for 3 or 8 days (n = 6-7/group). At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats.

The effect of coenzyme Q10 included by γ-cyclodextrin on the growth of fission yeast studied by microscope Raman spectroscopy

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Nishida, Tatsuro; Kaino, Tomohiro; Ikarashi, Ryo; Nakata, Daisuke; Terao, Keiji; Ando, Masahiro; Hamaguchi, Hiro-o.; Kawamukai, Makoto; Yamamoto, Tatsuyuki

2013-09-01

The inclusion complex of coenzyme Q10 (CoQ10) by γ-cyclodextrin (γ-CD), CoQ10-CD complex, was recently developed. The addition of the CoQ10-CD complex recovered the growth of a fission yeast mutant strain, Δdps1, which otherwise cannot grow well due to the lack of coenzyme Q producing ability. However, the oxygen consumption rate of this strain was not restored by the addition of the CoQ10-CD complex. The addition of two other anti-oxidative reagents, glutathione and ascorbic acid, also recovered the growth of the Δdps1 strain as well. These results indicated that the recovery of the growth of Δdps1 was brought about by the anti-oxidative property of CoQ10. The intensity of Raman spectra of Δdps1 at 1602 cm-1, which is prominently observed for the wild type of the fission yeast, was compared between before and after addition of the CoQ10-CD complex. The signal was very weakly observed for Δdps1 and did not increase in intensity by the addition of the CoQ10-CD complex. These results suggested the recovery of the growth of Δdps1 was brought about not by the restoration of respiration function of Δdps1 but by the anti-oxidative property of CoQ10 to result in the decrease in the oxidative stress.

Coenzyme Q10 Supplementation and Oocyte Aneuploidy in Women Undergoing IVF-ICSI Treatment

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Yaakov Bentov

2014-01-01

Full Text Available Background The age-related reduction in live-birth rate is attributed to a high rate of aneuploidy and follicle depletion. We showed in an animal model that treatment with Coenzyme Q10 (CoQ10 markedly improved reproductive outcome. The aim of this study was to compare the post-meiotic oocyte aneuploidy rate in in vitro fertilization (IVF and intra cytoplasmic sperm injection (ICSI patients treated with CoQ10 or placebo. Methods We conducted a double blind placebo controlled randomized trial that included IVF-ICSI patients 35-43 years of age. The patients were treated with either 600 mg of CoQ10 or an equivalent number of placebo caps. We compared the post-meiotic aneuploidy rate using polar body biopsy (PBBX and comparative genomic hybridization (CGH. According to the power calculation, 27 patients were needed for each arm. Results Owing to safety concerns regarding the effects of polar body biopsy on embryo quality and implantation, the study was terminated before reaching the target number of participants. A total of 39 patients were evaluated and randomized (17 CoQ10, 22 placebo, 27 were given the study medication (12 CoQ10, 15 placebo, and 24 completed an IVF-ICSI cycle including PBBX and embryo transfer (10 CoQ10, 14 placebo. Average age, base line follicle stimulating hormone (FSH, peak estradiol and progesterone serum level, as well as the total number of human menopausal gonadotropin (hMG units–-did not differ between the groups. The rate of aneuploidy was 46.5% in the CoQ10 group compared to 62.8% in the control. Clinical pregnancy rate was 33% for the CoQ10 group and 26.7% for the control group. Conclusion No significant differences in outcome were detected between the CoQ10 and placebo groups. However, the final study was underpowered to detect a difference in the rate of aneuploidy.

Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin.

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Ustuner, Mehmet Alperen; Kaman, Dilara; Colakoglu, Neriman

2017-12-01

Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats. Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli. The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

Coenzyme Q10 plus Multivitamin Treatment Prevents Cisplatin Ototoxicity in Rats.

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Laura Astolfi

Full Text Available Cisplatin (Cpt is known to induce a high level of oxidative stress, resulting in an increase of reactive oxygen species damaging the inner ear and causing hearing loss at high frequencies. Studies on animal models show that antioxidants may lower Cpt-induced ototoxicity. The aim of this study is to evaluate the ototoxic effects of two different protocols of Cpt administration in a Sprague-Dawley rat model, and to test in the same model the synergic protective effects of a solution of coenzyme Q10 terclatrate and Acuval 400®, a multivitamin supplement containing antioxidant agents and minerals (Acu-Qter. The Cpt was administered intraperitoneally in a single dose (14 mg/kg or in three daily doses (4.6 mg/kg/day to rats orally treated or untreated with Acu-Qter for 5 days. The auditory function was assessed by measuring auditory brainstem responses from 2 to 32 kHz at day 0 and 5 days after treatment. Similar hearing threshold and body weight alterations were observed in both Cpt administration protocols, but mortality reduced to zero when Cpt was administered in three daily doses. The Acu-Qter treatment was able to prevent and completely neutralize ototoxicity in rats treated with three daily Cpt doses, supporting the synergic protective effects of coenzyme Q terclatrate and Acuval 400® against Cpt-induced oxidative stress. The administration protocol involving three Cpt doses is more similar to common human chemotherapy protocols, therefore it appears more useful for long-term preclinical studies on ototoxicity prevention.

THE COMBINED EFFECT OF SCUTELLARIA BAICALENSIS EXTRACT AND COENZYME Q10 IN OXIDATIVE STRESS INDUCED BY CHROMIUM COMPOUNDS

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Ewa Sawicka

2010-03-01

Full Text Available Background: The common use of antioxidants and its joint application brings the question whether they are useful in oxidative stress induced by the chemicals or whether they cause harmful interaction. Both Scutellaria baicalensis and CoQ10 are known as antioxidants, however one exogenous, the second endogenous. Chromium belongs equal to essential microelements and toxic factors. Therefore the aim of work was the evaluation joint effect of two examined antioxidants in exposure to chromium compounds.Materials and methods: The material was fresh blood obtained from healthy volunteers. The concentration of malondialdehyde (MDA in erythrocytes was evaluated using Stock’s method. The activity of mixture of Antoxyd and coenzyme Q10 was tested after exposure to chromium III and VI at concentrations: 0,05; 0,5 and 1,0 µg/ml. Antioxidants were used in concentrations : 8,0; 20; 60 and 100 µg/ml. Results: The influence of coenzyme Q10 in exposure to chromium III and chromium VI was statistically insignificant, but CoQ10 given together with Antoxyd in all used concentration statistically significant decreased the level of MDA in erythrocytes exposed to chromium compounds (p*0,001. Conclusions: Application of both antioxidants has exerted synergistic action lowering MDA level, which was elevated after chromium. No harmful interactions in the examined sample between antioxidants and chromium ions were noted.

Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens.

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Urban Alehagen

Full Text Available Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD, and functional class.Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered.Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95%CI 0.36-0.74; P = 0.0003. The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95%CI 0.27-0.97; P = 0.04, but also in the different functional classes.In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

Coenzyme Q10 Status as a Determinant of Muscular Strength in Two Independent Cohorts.

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Alexandra Fischer

Full Text Available Aging is associated with sarcopenia, which is a loss of skeletal muscle mass and function. Coenzyme Q10 (CoQ10 is involved in several important functions that are related to bioenergetics and protection against oxidative damage; however, the role of CoQ10 as a determinant of muscular strength is not well documented. The aim of the present study was to evaluate the determinants of muscular strength by examining hand grip force in relation to CoQ10 status, gender, age and body mass index (BMI in two independent cohorts (n = 334, n = 967. Furthermore, peak flow as a function of respiratory muscle force was assessed. Spearman's correlation revealed a significant positive association between CoQ10/cholesterol level and hand grip in the basic study population (p<0.01 as well as in the validation population (p<0.001. In the latter, we also found a negative correlation with the CoQ10 redox state (p<0.01, which represents a lower percentage of the reduced form of CoQ10 (ubiquinol in subjects who exhibit a lower muscular strength. Furthermore, the age of the subjects showed a negative correlation with hand grip (p<0.001, whereas BMI was positively correlated with hand grip (p<0.01, although only in the normal weight subgroup (BMI <25 kg/m2. Analysis of the covariance (ANCOVA with hand grip as the dependent variable revealed CoQ10/cholesterol as a determinant of muscular strength and gender as the strongest effector of hand grip. In conclusion, our data suggest that both a low CoQ10/cholesterol level and a low percentage of the reduced form of CoQ10 could be an indicator of an increased risk of sarcopenia in humans due to their negative associations to upper body muscle strength, peak flow and muscle mass.

Coenzyme Q10 and soyphosphatidylcholine in EK extender on preservation of Rhode Island Red poultry semen

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Amit Kumar Nath

2015-06-01

Full Text Available The objective of this study was to evaluate the efficacy of EK extender alone or incorporation with CoenzymeQ10 (CoQ10 and/or soyphosphatidylcholine (SPC in poultry semen and their effects on seminal traits during temporal storage at 4⁰C for different time intervals (12 h, 24 h, and 36 h. Heterospermic pooled semen samples diluted (1:4 with EK, EK + SPC, EK+ CoQ10 and EK + SPC + CoQ10 extenders separately, preserved and different spermiogram were assessed. Various seminal traits within the same extender differ significantly (p<0.05 among different groups and with different time intervals of storage. CoQ10 and SPC in the EK extender exhibited favorable synergistic effect on sperm quality and were able to protect the male gametes against cold-stress up to 36h at 4⁰C. In this study, we concluded that incorporation of SPC and CoQ10 together in EK extender possess novel potentiality to maintain seminal quality during liquid storage of poultry semen at 4⁰C and for their safe transportation and further use for Artificial Reproductive technologies (ARTs.

Coenzyme Q10 Levels Are Decreased in the Cerebellum of Multiple-System Atrophy Patients.

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Lucia V Schottlaender

Full Text Available The objective of this study was to evaluate whether the levels of coenzyme Q10 (CoQ10 in brain tissue of multiple system atrophy (MSA patients differ from those in elderly controls and in patients with other neurodegenerative diseases.Flash frozen brain tissue of a series of 20 pathologically confirmed MSA patients [9 olivopontocerebellar atrophy (OPCA type, 6 striatonigral degeneration (SND type, and 5 mixed type] was used for this study. Elderly controls (n = 37 as well as idiopathic Parkinson's disease (n = 7, dementia with Lewy bodies (n = 20, corticobasal degeneration (n = 15 and cerebellar ataxia (n = 18 patients were used as comparison groups. CoQ10 was measured in cerebellar and frontal cortex tissue by high performance liquid chromatography.We detected a statistically significant decrease (by 3-5% in the level of CoQ10 in the cerebellum of MSA cases (P = 0.001, specifically in OPCA (P = 0.001 and mixed cases (P = 0.005, when compared to controls as well as to other neurodegenerative diseases [dementia with Lewy bodies (P<0.001, idiopathic Parkinson's disease (P<0.001, corticobasal degeneration (P<0.001, and cerebellar ataxia (P = 0.001].Our results suggest that a perturbation in the CoQ10 biosynthetic pathway is associated with the pathogenesis of MSA but the mechanism behind this finding remains to be elucidated.

Effect of dietary coenzyme Q10 supplementation on serum and bone minerals and leg weakness mortality in broilers

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M. Gopi

2014-05-01

Full Text Available Aim: This work was carried out to study the effect of coenzyme Q10 supplementation on serum calcium and phosphorus levels, tibial bone weight, bone ash, bone calcium and phosphorus levels and mortality of birds due to leg weakness when the broilers were maintained under high environmental temperature. Materials and Methods: The trial was carried out on 216 Cobb400 broiler chicks and divided into four groups with nine replicates and each replicate consisting of six birds. The treatments include normal energy diet (NE (as per breeder's specifications (G1, high energy (HE (NE plus 100 kcal/kg diet without CoQ10 supplementation (G2, high energy diet supplemented with CoQ10 at 20 mg/kg (G3 and high energy diet supplemented with CoQ10 at 40 mg/kg (G4. The experiment was carried out when the temperature humidity index (THI ranged from 33.05 to 38.65oC for a period of 42 days. Results: The serum calcium and phosphorus levels in the G1, G2, G3 and G4 were 9.07 ± 0.22, 8.48 ± 0.10, 8.30 ± 0.10, 8.32 ± 0.12 and 4.90 ± 0.20, 4.06 ± 0.32, 3.96 ± 0.17, 4.02 ± 0.24, respectively. The tibial bone weight (g was 21.58 ± 1.32, 17.92 ± 1.90, 18.67 ± 1.30 and 17.42 ± 1.18; tibial bone Ash (% 46.67 ± 2.71, 44.48 ± 2.40, 44.66 ± 3.09 and 44.62 ± 1.74; Bone calcium (% 33.57 ± 0.2, 31.27 ± 0.55, 31.50 ± 0.45 and 31.47 ± 0.83, bone phosphorus (% was 11.86 ± 0.16, 10.38 ± 0.11, 10.68 ± 0.08 and 10.39 ± 0.17, respectively in G1, G2, G3 and G4 groups. The serum calcium and phosphorus levels were significantly higher (P<0.05 in G1 over the other three groups. The tibial bone weight was not altered by the energy level or the coenzyme Q10 supplementation. The tibial bone calcium and phosphorus levels were significantly higher in G1 than the other three groups. Conclusion: The supplementation of coenzyme Q10 did not alter the serum and tibial bone calcium and phosphorus levels. The leg abnormality associated mortality was significantly decreased in G3

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

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Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

2017-07-26

Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate

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Samoudi, Mojtaba; Omid Yeganeh, Negar; Shahbani Zahiri, Hossein; Shariati, Parvin; Hajhosseini, Reza

2015-01-01

Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli). Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transform...

Effect of Simvastatin, Coenzyme Q10, Resveratrol, Acetylcysteine and Acetylcarnitine on Mitochondrial Respiration.

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Fišar, Z; Hroudová, J; Singh, N; Kopřivová, A; Macečková, D

2016-01-01

Some therapeutic and/or adverse effects of drugs may be related to their effects on mitochondrial function. The effects of simvastatin, resveratrol, coenzyme Q10, acetylcysteine, and acetylcarnitine on Complex I-, Complex II-, or Complex IV-linked respiratory rate were determined in isolated brain mitochondria. The protective effects of these biologically active compounds on the calcium-induced decrease of the respiratory rate were also studied. We observed a significant inhibitory effect of simvastatin on mitochondrial respiration (IC50 = 24.0 μM for Complex I-linked respiration, IC50 = 31.3 μM for Complex II-linked respiration, and IC50 = 42.9 μM for Complex IV-linked respiration); the inhibitory effect of resveratrol was found at very high concentrations (IC50 = 162 μM for Complex I-linked respiration, IC50 = 564 μM for Complex II-linked respiration, and IC50 = 1454 μM for Complex IV-linked respiration). Concentrations required for effective simvastatin- or resveratrol-induced inhibition of mitochondrial respiration were found much higher than concentrations achieved under standard dosing of these drugs. Acetylcysteine and acetylcarnitine did not affect the oxygen consumption rate of mitochondria. Coenzyme Q10 induced an increase of Complex I-linked respiration. The increase of free calcium ions induced partial inhibition of the Complex I+II-linked mitochondrial respiration, and all tested drugs counteracted this inhibition. None of the tested drugs showed mitochondrial toxicity (characterized by respiratory rate inhibition) at drug concentrations achieved at therapeutic drug intake. Resveratrol, simvastatin, and acetylcarnitine had the greatest neuroprotective potential (characterized by protective effects against calcium-induced reduction of the respiratory rate).

Free radical scavenging activity of coenzyme Q measured by a chemiluminescent assay

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Battino, Maurizio; Ferri, Elida; Girotti, Stefano; Lenaz, Giorgio

1991-01-01

Involvement of coenzyme Q (CoQ) in anti-oxydant activities, in addition to its major redox role, has frequently been suggested in recent years. In order to elucidate if CoQ could really be engaged in scavenging free radicals produced endogenously in a biological system, an experimental system was developed in which beef heart mitochondria in the presence of a saturating NADH concentration and of rotenone produce free radicals. The presence of oxygen-reactive forms was easily detected by a luminol-dependent chemiluminescence process. The chemi-luminescence assay showed that short-chain CoQ homologues can act as pro-oxidants, enhancing free radical effects, while exogenous coenzyme Q 10 could scavenge free radicals, especially at very low concentration. In this system, exogenous CoQ 10 was more effective than α-tocopherol at the same concentration in scavenging free radicals. The molecular mechanism that leads to this activity is still unclear, but these results are of biochemical importance because they indicate that CoQ may act as an anti=oxidant in situations mimicking physiopathological conditions. This direct chemiluminescent method is promising for studies of biochemical processes which involve active oxygen species. (author). 24 refs.; 4 figs

Application of Coenzyme Q10 for Accelerating Soft Tissue Wound Healing after Tooth Extraction in Rats

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Toshiki Yoneda

2014-12-01

Full Text Available Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10, may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old (n = 27 received topical application of ointment containing 5% rCoQ10 (experimental group or control ointment (control group to the sockets for 3 or 8 days (n = 6–7/group. At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p < 0.05. Gene expression of interleukin-1β, tumor necrosis factor-α and nuclear factor-κB were also lower in the experimental group than in the control group (p < 0.05. At 8 days after tooth extraction, there were no significant differences in collagen density, number of polymorphonuclear leukocytes and bone fill between the groups. Our results suggest that topical application of rCoQ10 promotes wound healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats.

Coenzyme Q10 and its effects in the treatment of neurodegenerative diseases

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Graciela Cristina dos Santos

2009-12-01

Full Text Available According to clinical and pre-clinical studies, oxidative stress and its consequences may be the cause or, at least, a contributing factor, to a large number of neurodegenerative diseases. These diseases include common and debilitating disorders, characterized by progressive and irreversible loss of neurons in specific regions of the brain. The most common neurodegenerative diseases are Parkinson's disease, Huntington's disease, Alzheimer's disease and amyotrophic lateral sclerosis. Coenzyme Q10 (CoQ10 has been extensively studied since its discovery in 1957. It is a component of the electron transportation chain and participates in aerobic cellular respiration, generating energy in the form of adenosine triphosphate (ATP. The property of CoQ10 to act as an antioxidant or a pro-oxidant, suggests that it also plays an important role in the modulation of redox cellular status under physiological and pathological conditions, also performing a role in the ageing process. In several animal models of neurodegenerative diseases, CoQ10 has shown beneficial effects in reducing disease progression. However, further studies are needed to assess the outcome and effectiveness of CoQ10 before exposing patients to unnecessary health risks at significant costs.De acordo com estudos clínicos e pré-clínicos, o estresse oxidativo e suas conseqüências podem ser a causa, ou, no mínimo, o fator que contribui para grande número de doenças degenerativas. Estas doenças incluem problemas comuns e debilitantes, caracterizados por perda progressiva e irreversível de neurônios em regiões específicas do cérebro. As doenças degenerativas mais comuns são doença de Parkinson, de Hutington, de Alzheimer e esclerose amiotrófica lateral. A Coenzima Q10 (CoQ10 tem sido intensamente estudada desde sua descoberta, em 1957. É um componente da cadeia de transporte eletrônico e participa da respiração aeróbica celular, gerando energia na forma de trifosfato de

Primary coenzyme Q deficiency in Pdss2 mutant mice causes isolated renal disease.

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Min Peng

2008-04-01

Full Text Available Coenzyme Q (CoQ is an essential electron carrier in the respiratory chain whose deficiency has been implicated in a wide variety of human mitochondrial disease manifestations. Its multi-step biosynthesis involves production of polyisoprenoid diphosphate in a reaction that requires the enzymes be encoded by PDSS1 and PDSS2. Homozygous mutations in either of these genes, in humans, lead to severe neuromuscular disease, with nephrotic syndrome seen in PDSS2 deficiency. We now show that a presumed autoimmune kidney disease in mice with the missense Pdss2(kd/kd genotype can be attributed to a mitochondrial CoQ biosynthetic defect. Levels of CoQ9 and CoQ10 in kidney homogenates from B6.Pdss2(kd/kd mutants were significantly lower than those in B6 control mice. Disease manifestations originate specifically in glomerular podocytes, as renal disease is seen in Podocin/cre,Pdss2(loxP/loxP knockout mice but not in conditional knockouts targeted to renal tubular epithelium, monocytes, or hepatocytes. Liver-conditional B6.Alb/cre,Pdss2(loxP/loxP knockout mice have no overt disease despite demonstration that their livers have undetectable CoQ9 levels, impaired respiratory capacity, and significantly altered intermediary metabolism as evidenced by transcriptional profiling and amino acid quantitation. These data suggest that disease manifestations of CoQ deficiency relate to tissue-specific respiratory capacity thresholds, with glomerular podocytes displaying the greatest sensitivity to Pdss2 impairment.

Coenzyme Q10, α-Tocopherol, and Oxidative Stress Could Be Important Metabolic Biomarkers of Male Infertility

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Anna Gvozdjáková

2015-01-01

Full Text Available Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10,  CoQ10-TOTAL, γ, and α-tocopherols, and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp. and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ10-TOTAL (ubiquinone + ubiquinol and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ10-TOTAL, and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.

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Junya Zhai

Full Text Available Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10 has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases.Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs. The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6, tumor necrosis factor-alpha (TNF-α and C reactive protein (CRP. RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software.Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87 μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24 pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17 mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16 pg/ml, I2 = 84%].CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.

Coenzyme Q10 Inhibits the Aging of Mesenchymal Stem Cells Induced by D-Galactose through Akt/mTOR Signaling

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Dayong Zhang

2015-01-01

Full Text Available Increasing evidences indicate that reactive oxygen species are the main factor promoting stem cell aging. Recent studies have demonstrated that coenzyme Q10 (CoQ10 plays a positive role in organ and cellular aging. However, the potential for CoQ10 to protect stem cell aging has not been fully evaluated, and the mechanisms of cell senescence inhibited by CoQ10 are still poorly understood. Our previous study had indicated that D-galactose (D-gal can remarkably induce mesenchymal stem cell (MSC aging through promoting intracellular ROS generation. In this study, we showed that CoQ10 could significantly inhibit MSC aging induced by D-gal. Moreover, in the CoQ10 group, the expression of p-Akt and p-mTOR was clearly reduced compared with that in the D-gal group. However, after Akt activating by CA-Akt plasmid, the senescence-cell number in the CoQ10 group was significantly higher than that in the control group. These results indicated that CoQ10 could inhibit D-gal-induced MSC aging through the Akt/mTOR signaling.

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

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Hsiao-Ya Tsai

2016-01-01

Full Text Available Coenzyme Q10 (CoQ10, an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM or high glucose (25 mM enviroment for 3 days, followed by treatment with CoQ10 (10 μM for 24 hr. Cell proliferation, nitric oxide (NO production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK, eNOS/Akt, and heme oxygenase-1 (HO-1 were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

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Tsai, Hsiao-Ya; Lin, Chih-Pei; Huang, Po-Hsun; Li, Szu-Yuan; Chen, Jia-Shiong; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

2016-01-01

Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID:26682233

Coenzyme Q10 protects retinal cells from apoptosis induced by radiation in vitro and in vivo

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Lulli, M.; Witort, E.; Papucci, L.; Torre, E.; Schiavone, N.; Capaccioli, S.; Dal Monte, M.

2012-01-01

The key pathogenetic event of many retinopathies is apoptosis of retinal cells. Our previous studies have demonstrated that Coenzyme Q10 (CoQ10) prevents apoptosis of corneal keratocytes both in vitro and in vivo, by virtue of its ability to inhibit mitochondrial depolarization, independently of its free radical scavenger role. The aim of this study was to evaluate whether CoQ10 can protect cultured retinal cells and the retinas of rats from radiation-induced apoptosis, if instilled as eye drops in the cornea. In vitro experiments were carried out on cultured ARPE-19 or retinal ganglion cells (RGC)-5 cells pretreated with CoQ10 before eliciting apoptosis by ultraviolet (UV)- and γ-radiation, chemical hypoxia (Antimycin A) and serum starvation. Cell viability was evaluated by light microscopy and fluorescence activated cell sorting analysis. Apoptotic events were scored by time-lapse videomicroscopy. Mitochondrial permeability transition was evaluated by JC-1. The anti-apoptotic effectiveness of CoQ10 in retina was also evaluated by an in situ end-labeling assay in Wistar albino rats treated with CoQ10 eye drops prior to UV irradiation of the eye. CoQ10 substantially increased cell viability and lowered retinal cell apoptosis in response both to UV- and γ-radiation and to chemical hypoxia or serum starvation by inhibiting mitochondrion depolarization. In the rat, CoQ10, even when applied as eye drops on the cornea, protected all retina layers from ultraviolet radiation (UVR)-induced apoptosis. The ability of CoQ10 to protect retinal cells from radiation-induced apoptosis following its instillation on the cornea suggests the possibility for CoQ10 eye drops to become a future therapeutic countermeasure for radiation-induced retinal lesions. (author)

Improvement of Coenzyme Q10 Production: Mutagenesis Induced by High Hydrostatic Pressure Treatment and Optimization of Fermentation Conditions

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Yahong Yuan

2012-01-01

Full Text Available Coenzyme Q10 (CoQ10, ubiquinone, a potent antioxidative dietary supplement, was produced by submerged fermentation using Agrobacterium tumefaciens instead of chemical synthesis or solvent extraction. Agrobacterium tumefaciens 1.2554 was subjected to mutagenesis using a series of treatments including high hydrostatic pressure (HHP treatment, UV irradiation, and diethyl sulfate (DES treatment to obtain mutant strains showing higher CoQ10 production than wild-type strains. A mutant strain PK38 with four genetic markers was isolated: the specific CoQ10 content of the mutant strain increased by 52.83% compared with the original strain. Effects of carbon and nitrogen sources on CoQ10 production with PK38 were studied. Sucrose at concentration of 30 g/l was tested as the best carbon source, and yeast extract at concentration of 30 g/l supplemented with 10 g/l of ammonium sulfate was identified to be the most favorable for CoQ10 production using PK38. Fed-batch culture strategy was then used for increasing production of CoQ10 in 5-l fermentor. Using the exponential feeding fed-batch culture of sucrose, cell growth and CoQ10 formation were significantly improved. With this strategy, the final cell biomass, CoQ10 production, and specific CoQ10 production increased by 126.11, 173.12, and 22.76%, respectively, compared to those of batch culture.

Border between natural product and drug: Comparison of the related benzoquinones idebenone and coenzyme Q10

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Nuri Gueven

2015-04-01

Full Text Available Coenzyme Q10 is a ubiquitous component of cellular membranes and belongs to the class of benzoquinones that mainly differ with regards to the length and composition of their hydrophobic tail. The characteristic quinone group can accept electrons from various biological sources and is converted by a one electron transfer to the unstable semiquinone or by a two electron transfer to the more stable hydroquinone. This feature makes CoQ10 the bona fide cellular electron transfer molecule within the mitochondrial respiratory chain and also makes it a potent cellular antioxidant. These activities serve as justification for its popular use as food supplement. Another quinone with similarities to the naturally occurring CoQ10 is idebenone, which shares its quinone moiety with CoQ10, but at the same time differs from CoQ10 by the presence of a much shorter, less lipophilic tail. However, despite its similarity to CoQ10, idebenone cannot be isolated from any natural sources but instead was synthesized and selected as a pharmacologically active compound in the 1980s by Takeda Pharmaceuticals purely based on its pharmacological properties. Several recent clinical trials demonstrated some therapeutic efficacy of idebenone in different indications and as a consequence, many practitioners question if the freely available CoQ10 could not be used instead. Here, we describe the molecular and pharmacological features of both molecules that arise from their structural differences to answer the question if idebenone is merely a CoQ10 analogue as frequently perpetuated in the literature or a pharmaceutical drug with entirely different features.

Oxidative Stress Correlates with Headache Symptoms in Fibromyalgia: Coenzyme Q10 Effect on Clinical Improvement

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Cordero, Mario D.; Cano-García, Francisco Javier; Alcocer-Gómez, Elísabet; De Miguel, Manuel; Sánchez-Alcázar, José Antonio

2012-01-01

Background Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q10 (CoQ10) supplementation on biochemical markers and clinical improvement were also evaluated. Methods We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ10, catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. Results We found decreased CoQ10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P<0.05 and P<0.001, respectively) We also found increased level of LPO in BMCs from FM patients as compared to normal control (P<0.001). Significant negative correlations between CoQ10 or catalase levels in BMCs and headache parameters were observed (r = −0.59, P<0.05; r = −0.68, P<0.05, respectively). Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05). Oral CoQ10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P<0.001). Discussion The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM. PMID:22532869

Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble Coenzyme Q10

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McCarthy, S.; Somayajulu, M.; Sikorska, M.; Borowy-Borowski, H.; Pandey, S.

2004-01-01

Neuronal cell death induced by oxidative stress is correlated with numerous neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The causes of sporadic forms of age-related neurodegenerative diseases are still unknown. Recently, a correlation between paraquat exposure and neurodegenerative diseases has been observed. Paraquat, a nonselective herbicide, was once widely used in North America and is still routinely used in Taiwan. We have used differentiated Human Neuroblastoma (SHSY-5Y) cells as an in vitro model to study the mechanism of cell death induced by paraquat. We observed that paraquat-induced oxidative stress in differentiated SHSY-5Y cells as indicated by an increase in the production of cellular reactive oxygen species (ROS). Furthermore, apoptosis was evident as indicated by cellular and nuclear morphology and DNA fragmentation. Interestingly, pretreatment of SHSY-5Y cells with water-soluble Coenzyme Q 10 (CoQ 10 ) before paraquat exposure inhibited ROS generation. Pretreatment with CoQ 10 also significantly reduced the number of apoptotic cells and DNA fragmentation. We also analyzed the effect of paraquat and CoQ 10 on isolated mitochondria. Our results indicated that treatment with paraquat induced the generation of ROS from isolated mitochondria and depolarization of the inner mitochondrial membrane. Pretreatment with CoQ 10 was able to inhibit ROS generation from isolated mitochondria as well as the collapse of mitochondrial membrane potential. Our results indicate that water-soluble CoQ 10 can prevent oxidative stress and neuronal damage induced by paraquat and therefore, can be used for the prevention and therapy of neurodegenerative diseases caused by environmental toxins

A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit.

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Beal, M Flint; Oakes, David; Shoulson, Ira; Henchcliffe, Claire; Galpern, Wendy R; Haas, Richard; Juncos, Jorge L; Nutt, John G; Voss, Tiffini Smith; Ravina, Bernard; Shults, Clifford M; Helles, Karen; Snively, Victoria; Lew, Mark F; Griebner, Brian; Watts, Arthur; Gao, Shan; Pourcher, Emmanuelle; Bond, Louisette; Kompoliti, Katie; Agarwal, Pinky; Sia, Cherissa; Jog, Mandar; Cole, Linda; Sultana, Munira; Kurlan, Roger; Richard, Irene; Deeley, Cheryl; Waters, Cheryl H; Figueroa, Angel; Arkun, Ani; Brodsky, Matthew; Ondo, William G; Hunter, Christine B; Jimenez-Shahed, Joohi; Palao, Alicia; Miyasaki, Janis M; So, Julie; Tetrud, James; Reys, Liza; Smith, Katharine; Singer, Carlos; Blenke, Anita; Russell, David S; Cotto, Candace; Friedman, Joseph H; Lannon, Margaret; Zhang, Lin; Drasby, Edward; Kumar, Rajeev; Subramanian, Thyagarajan; Ford, Donna Stuppy; Grimes, David A; Cote, Diane; Conway, Jennifer; Siderowf, Andrew D; Evatt, Marian Leslie; Sommerfeld, Barbara; Lieberman, Abraham N; Okun, Michael S; Rodriguez, Ramon L; Merritt, Stacy; Swartz, Camille Louise; Martin, W R Wayne; King, Pamela; Stover, Natividad; Guthrie, Stephanie; Watts, Ray L; Ahmed, Anwar; Fernandez, Hubert H; Winters, Adrienna; Mari, Zoltan; Dawson, Ted M; Dunlop, Becky; Feigin, Andrew S; Shannon, Barbara; Nirenberg, Melissa Jill; Ogg, Mattson; Ellias, Samuel A; Thomas, Cathi-Ann; Frei, Karen; Bodis-Wollner, Ivan; Glazman, Sofya; Mayer, Thomas; Hauser, Robert A; Pahwa, Rajesh; Langhammer, April; Ranawaya, Ranjit; Derwent, Lorelei; Sethi, Kapil D; Farrow, Buff; Prakash, Rajan; Litvan, Irene; Robinson, Annette; Sahay, Alok; Gartner, Maureen; Hinson, Vanessa K; Markind, Samuel; Pelikan, Melisa; Perlmutter, Joel S; Hartlein, Johanna; Molho, Eric; Evans, Sharon; Adler, Charles H; Duffy, Amy; Lind, Marlene; Elmer, Lawrence; Davis, Kathy; Spears, Julia; Wilson, Stephanie; Leehey, Maureen A; Hermanowicz, Neal; Niswonger, Shari; Shill, Holly A; Obradov, Sanja; Rajput, Alex; Cowper, Marilyn; Lessig, Stephanie; Song, David; Fontaine, Deborah; Zadikoff, Cindy; Williams, Karen; Blindauer, Karen A; Bergholte, Jo; Propsom, Clara Schindler; Stacy, Mark A; Field, Joanne; Mihaila, Dragos; Chilton, Mark; Uc, Ergun Y; Sieren, Jeri; Simon, David K; Kraics, Lauren; Silver, Althea; Boyd, James T; Hamill, Robert W; Ingvoldstad, Christopher; Young, Jennifer; Thomas, Karen; Kostyk, Sandra K; Wojcieszek, Joanne; Pfeiffer, Ronald F; Panisset, Michel; Beland, Monica; Reich, Stephen G; Cines, Michelle; Zappala, Nancy; Rivest, Jean; Zweig, Richard; Lumina, L Pepper; Hilliard, Colette Lynn; Grill, Stephen; Kellermann, Marye; Tuite, Paul; Rolandelli, Susan; Kang, Un Jung; Young, Joan; Rao, Jayaraman; Cook, Maureen M; Severt, Lawrence; Boyar, Karyn

2014-05-01

Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. To examine whether CoQ10 could slow disease progression in early PD. A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants

Calcium binding and transport by coenzyme Q.

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Bogeski, Ivan; Gulaboski, Rubin; Kappl, Reinhard; Mirceski, Valentin; Stefova, Marina; Petreska, Jasmina; Hoth, Markus

2011-06-22

Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV-vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography-mass spectrometry (HPLC-MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca(2+) across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca(2+) and redox homeostasis.

Effects of coenzyme Q10 on statin-induced myopathy: a meta-analysis of randomized controlled trials.

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Banach, Maciej; Serban, Corina; Sahebkar, Amirhossein; Ursoniu, Sorin; Rysz, Jacek; Muntner, Paul; Toth, Peter P; Jones, Steven R; Rizzo, Manfredi; Glasser, Stephen P; Lip, Gregory Y H; Dragan, Simona; Mikhailidis, Dimitri P

2015-01-01

To evaluate the efficacy of coenzyme Q10 (CoQ10) supplementation on statin-induced myopathy. We searched the MEDLINE, Cochrane Library, Scopus, and EMBASE databases (November 1, 1987, to May 1, 2014) to identify randomized controlled trials investigating the impact of CoQ10 on muscle pain and plasma creatine kinase (CK) activity as 2 measures of statin-induced myalgia. Two independent reviewers extracted data on study characteristics, methods, and outcomes. We included 6 studies with 302 patients receiving statin therapy: 5 studies with 226 participants evaluated the effect of CoQ10 supplementation on plasma CK activity, and 5 studies (4 used in the CK analysis and 1 other study) with 253 participants were included to assess the effect of CoQ10 supplementation on muscle pain. Compared with the control group, plasma CK activity was increased after CoQ10 supplementation, but this change was not significant (mean difference, 11.69 U/L [to convert to μkat/L, multiply by 0.0167]; 95% CI, -14.25 to 37.63 U/L; P=.38). Likewise, CoQ10 supplementation had no significant effect on muscle pain despite a trend toward a decrease (standardized mean difference, -0.53; 95% CI, -1.33 to 0.28; P=.20). No dose-effect association between changes in plasma CK activity (slope, -0.001; 95% CI, -0.004 to 0.001; P=.33) or in the indices of muscle pain (slope, 0.002; 95% CI, -0.005 to 0.010; P=.67) and administered doses of CoQ10 were observed. The results of this meta-analysis of available randomized controlled trials do not suggest any significant benefit of CoQ10 supplementation in improving statin-induced myopathy. Larger, well-designed trials are necessary to confirm the findings from this meta-analysis. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome

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Cuiwen H. He

2017-07-01

Full Text Available Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. We found that expression of human COQ9 rescues the growth of the temperature-sensitive yeast mutant, coq9-ts19, on a non-fermentable carbon source and increases the content of Q6, by enhancing Q biosynthesis from 4-hydroxybenzoic acid (4HB. To study the mechanism for the rescue by human COQ9, we determined the steady-state levels of yeast Coq polypeptides in the mitochondria of the temperature-sensitive yeast coq9 mutant expressing human COQ9. We show that the expression of human COQ9 significantly increased steady-state levels of yeast Coq4, Coq6, Coq7, and Coq9 at permissive temperature. Human COQ9 polypeptide levels persisted at non-permissive temperature. A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model.

CoQ10 plasmatic levels in breast-fed infants compared to formula-fed infants.

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Compagnoni, G; Giuffrè, B; Lista, G; Mosca, F; Marini, A

2004-01-01

Coenzyme Q10 has been recognized as an important antioxidant factor besides its main role in bioenergetic metabolism. CoQ10 tissue levels depend both on exogenous dietetic intake and on endogenous biosynthesis, as this compound can be partly synthesized in human cells. Q10 plasma levels reflect the tissue content of the coenzyme and can be used to evaluate the presence of this compound in the human organism. Aim of the study was to measure CoQ10 plasmatic levels in a newborn breast-fed population and to compare them to CoQ10 levels in a newborn formula-fed population in order to verify whether changes in CoQ10 plasmatic contents could be related to a different dietetic intakes. We measured CoQ10 plasmatic levels in 25 healthy term neonates with different dietetic intakes: 15 breast-fed and 10 bottle-fed with a common infant formula. These infants were evaluated prospectively during the first month of life. The analyses were performed on the mothers' blood samples and cord blood samples at the time of delivery, then on infants at 4 and 28 days of age. Our results showed markedly reduced Q10 levels in cord blood samples compared to maternal Q10 plasmatic levels at the time of delivery, suggesting placental impermeability towards this molecule or increased fetal utilization during labor and delivery. At 4 days of age Q10 levels had increased in both groups of neonates, but significantly more in breast-fed infants compared to formula-fed babies (p <0.05). At 4 weeks of age no significant changes occurred in breast-fed infants, while values increased significantly in formula-fed infants (p <0.05). The content of Q10 in breast milk samples was lower than in infant formula. The results of this study show that CoQ10 plasmatic levels are at least partly influenced by the exogenous dietetic supply.

Effect of DHA and CoenzymeQ10 Against Aβ- and Zinc-Induced Mitochondrial Dysfunction in Human Neuronal Cells

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Nadia Sadli

2013-07-01

Full Text Available Background: Beta-amyloid (Aβ protein is a key factor in the pathogenesis of Alzheimer's disease (AD and it has been reported that mitochondria is involved in the biochemical pathway by which Aβ can lead to neuronal dysfunction. Coenzyme Q10 (CoQ10 is an essential cofactor involved in the mitochondrial electron transport chain and has been suggested as a potential therapeutic agent in AD. Zinc toxicity also affects cellular energy production by decreasing oxygen consumption rate (OCR and ATP turnover in human neuronal cells, which can be restored by the neuroprotective effect of docosahexaenoic acid (DHA. Method: In the present study, using Seahorse XF-24 Metabolic Flux Analysis we investigated the effect of DHA and CoQ10 alone and in combination against Aβ- and zinc-mediated changes in the mitochondrial function of M17 neuroblastoma cell line. Results: Here, we observed that DHA is specifically neuroprotective against zinc-triggered mitochondrial dysfunction, but does not directly affect Aβ neurotoxicity. CoQ10 has shown to be protective against both Aβ- and zinc-induced alterations in mitochondrial function. Conclusion: Our results indicate that DHA and CoQ10 may be useful for the prevention, treatment and management of neurodegenerative diseases such as AD.

HYPOLIPIDEMIC EFFECT OF CURCUMIN OR CO-ENZYME Q1-0 AND THEIR MIXTURE ON OBESE RATS FED A HIGH CHOLESTEROL DIET

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SHAHIN, M.I.M.

2008-01-01

In the current study, hyperlipidemia was induced in the rats by feeding diet enriched with cholesterol for two weeks. After 2 weeks of induction of hypercholesterolemia in rats and in comparison to normal rats, the results showed that incorporation of extra cholesterol in diet led to significant increases in serum cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, leptin and MDA levels. On the other hand, total serum triiodothyronine (T3), liver glutathione (GSH) and glutathione peroxidase (GPx) activities were decreased significantly in cholesterol fed rats. The concentration of TBARS in the liver was elevated.All previous parameters were corrected after the hypercholesterolemic rats were treated with curcumin or co-enzyme Q 1 -0 or a mixture of them dependent on the time of treatment. These findings are consistent with the concept that curcumin and co-enzyme Q 10 are antioxidant agents. The underlying mechanisms of these effects were discussed

Treatment of cyclic vomiting syndrome with co-enzyme Q10 and amitriptyline, a retrospective study

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Preston Amy

2010-01-01

Full Text Available Abstract Background Cyclic vomiting syndrome (CVS, which is defined by recurrent stereotypical episodes of nausea and vomiting, is a relatively-common disabling condition that is associated with migraine headache and mitochondrial dysfunction. Co-enzyme Q10 (Co-Q is a nutritional supplement that has demonstrated efficacy in pediatric and adult migraine. It is increasingly used in CVS despite the complete lack of studies to demonstrate its value in treatment Methods Using an Internet-based survey filled out by subjects with CVS or their parents, the efficacy, tolerability and subject satisfaction in CVS prophylaxis were queried. Subjects taking Co-Q (22 subjects were compared against those taking amitriptyline (162 subjects, which is the general standard-of-care. Results Subjects/parents reported similar levels of efficacy for a variety of episode parameters (frequency, duration, number of emesis, nausea severity. There was a 50% reduction in at least one of those four parameters in 72% of subjects treated with amitriptyline and 68% of subjects treated Co-Q. However, while no side effects were reported on Co-Q, 50% of subjects on amitriptyline reported side effects (P = 5 × 10-7, resulting in 21% discontinuing treatment (P = 0.007. Subjects/parents considered the benefits to outweigh the risks of treatment in 47% of cases on amitriptyline and 77% of cases on Co-Q (P = 0.008. Conclusion Our data suggest that the natural food supplement Co-Q is potentially efficacious and tolerable in the treatment of CVS, and should be considered as an option in CVS prophylaxis. Our data would likely be helpful in the design of a double-blind clinical trial.

Coenzyme Q10 partially restores pathological alterations in a macrophage model of Gaucher disease.

Science.gov (United States)

de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Villanueva-Paz, Marina; de Lavera, Isabel; Álvarez-Córdoba, Mónica; Luzón-Hidalgo, Raquel; Suárez-Rivero, Juan M; Tiscornia, Gustavo; Sánchez-Alcázar, José A

2017-02-06

Gaucher disease (GD) is caused by mutations in the GBA1 gene which encodes lysosomal β-glucocerebrosidase (GCase). In GD, partial or complete loss of GCase activity causes the accumulation of the glycolipids glucosylceramide (GlcCer) and glucosylsphingosine in the lysosomes of macrophages. In this manuscript, we investigated the effects of glycolipids accumulation on lysosomal and mitochondrial function, inflammasome activation and efferocytosis capacity in a THP-1 macrophage model of Gaucher disease. In addition, the beneficial effects of coenzyme Q 10 (CoQ) supplementation on cellular alterations were evaluated. Chemically-induced Gaucher macrophages were developed by differentiateing THP-1 monocytes to macrophages by treatment with phorbol 12-myristate 13-acetate (PMA) and then inhibiting intracellular GCase with conduritol B-epoxide (CBE), a specific irreversible inhibitor of GCase activity, and supplementing the medium with exogenous GlcCer. This cell model accumulated up to 16-fold more GlcCer compared with control THP-1 cells. Chemically-induced Gaucher macrophages showed impaired autophagy flux associated with mitochondrial dysfunction and increased oxidative stress, inflammasome activation and impaired efferocytosis. All abnormalities were partially restored by supplementation with CoQ. These data suggest that targeting mitochondria function and oxidative stress by CoQ can ameliorate the pathological phenotype of Gaucher cells. Chemically-induced Gaucher macrophages provide cellular models that can be used to investigate disease pathogenesis and explore new therapeutics for GD.

Preparation, characterization and in silico modeling of biodegradable nanoparticles containing cyclosporine A and coenzyme Q10

Energy Technology Data Exchange (ETDEWEB)

Ankola, D D; Ravi Kumar, M N V [Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR (United Kingdom); Durbin, E W [Department of Physics, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 (United States); Buxton, G A [Department of Sciences, Robert Morris University, 6001 University Boulevard, Moon Township, PA 15108 (United States); Schaefer, J; Bakowsky, U, E-mail: mnvrkumar@strath.ac.uk [Department of Pharmaceutics and Biopharmacy, Philipps Universitt, 35037 Marburg (Germany)

2010-02-10

Combination therapy will soon become a reality, particularly for those patients requiring poly-therapy to treat co-existing disease states. This becomes all the more important with the increasing cost, time and complexity of the drug discovery process prompting one to look at new delivery systems to increase the efficacy, safety and patient compliance of existing drugs. Along this line, we attempted to design nano-scale systems for simultaneous encapsulation of cyclosporine A (CsA) and coenzyme Q10 (CoQ10) and model their encapsulation and release kinetics. The in vitro characterization of the co-encapsulated nanoparticles revealed that the surfactant nature, concentration, external phase volume, droplet size reduction method and drug loading concentration can all influence the overall performance of the nanoparticles. The semi-quantitative solubility study indicates the strong influence of CoQ10 on CsA entrapment which was thought to be due to an increase in the lipophilicity of the overall system. The in vitro dissolution profile indicates the influence of CoQ10 on CsA release (64%) to that of individual particles of CsA, where the release is faster and higher (86%) on 18th day. The attempts to model the encapsulation and release kinetics were successful, offering a possibility to use such models leading to high throughput screening of drugs and their nature, alone or in combination for a particular polymer, if chi-parameters are understood.

New evidences of neurotoxicity of aroclor 1254 in mice brain: potential of coenzyme q10 in abating the detrimental outcomes

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Anuradha Majumdar

2014-03-01

Full Text Available Objectives The present subacute study was designed to evaluate the effect of coenzyme Q 10 (CoQ10 in the 28 days aroclor 1254 exposure induced oxidative stress in mice brain. Methods Biochemical estimations of brain lipid peroxidation (LPO, reduced glutathione (GSH, and activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx and acetyl cholinesterase (AChE, and histopathological investigations of brain tissue were carried out. Results Oral exposure of aroclor 1254 (5 mg/kg led to significant decrease in levels of GSH, and activities of SOD, CAT, GPx, and AChE, and increase in LPO. These aberrations were restored by CoQ10 (10 mg/kg, intraperitoneal injection [IP]. This protection offered was comparable to that of L-deprenyl (1 mg/kg, IP which served as a reference standard. Conclusions Aroclor 1254 exposure hampers the activities of various antioxidant enzymes and induces oxidative stress in the brains of Swiss albino mice. Supplementation of CoQ10 abrogates these deleterious effects of aroclor 1254. CoQ10 also apparently enhanced acetyl cholinesterase activity which reflects its influence on the cholinergic system.

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency

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Neal Sondheimer

2017-09-01

Full Text Available Coenzyme Q10 (CoQ10 or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10–dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ10 biosynthesis. To date, mutations in COQ1 (PDSS1 and PDSS2, COQ2, COQ4, COQ6, COQ7, COQ8A/ADCK3, COQ8B/ADCK4, and COQ9 genes have been identified in patients with primary form of CoQ10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ10 deficiency.

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency.

Science.gov (United States)

Sondheimer, Neal; Hewson, Stacy; Cameron, Jessie M; Somers, Gino R; Broadbent, Jane Dunning; Ziosi, Marcello; Quinzii, Catarina Maria; Naini, Ali B

2017-09-01

Coenzyme Q 10 (CoQ 10 ) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ 10 synthesis are usually associated with the impaired function of CoQ 10 -dependent complexes I, II and III. The recessively transmitted CoQ 10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infantile, multisystemic presentation is usually caused by mutations in genes directly involved in CoQ 10 biosynthesis. To date, mutations in COQ1 ( PDSS1 and PDSS2 ), COQ2 , COQ4 , COQ6 , COQ7 , COQ8A / ADCK3 , COQ8B/ADCK4 , and COQ9 genes have been identified in patients with primary form of CoQ 10 deficiency. Here we report novel mutations in the COQ4 gene, which were identified in an infant with profound mitochondrial disease presenting with perinatal seizures, hypertrophic cardiomyopathy and severe muscle CoQ 10 deficiency.

Antioxidant vitamins C, E and coenzyme Q10 vs Dexamethasone: comparisons of their effects in pulmonary contusion model

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Gokce Mertol

2012-09-01

Full Text Available Abstract Background The goal of our study is to evaluate the effects of antioxidant vitamins (vitamin C and E, Coenzyme Q10 (CoQ10 and dexamethasone (Dxm in experimental rat models with pulmonary contusion (PC. Methods Rats were randomly divided into six groups. Except for the control, all subgroups had a moderate pulmonary contusion. Animals in the group I and group II received intraperitoneal saline, group III received 10mg.kg-1 CoQ10 group IV received 100mg.kg-1 vitamin C, group V received 150mg.kg-1 vitamin E, and group VI received 10mg.kg-1 Dxm. Blood gas analysis, serum nitric oxide (NO and malondialdehyde (MDA levels as well as superoxide dismutase (SOD activity assays, bronchoalveolar lavage (BAL fluid and histopathological examination were performed. Results Administration of CoQ10 resulted in a significant increase in PaO2 values compared with the group I (p = 0.004. Levels of plasma MDA in group II were significantly higher than those in the group I (p = 0.01. Early administration of vitamin C, CoQ10, and Dxm significantly decreased the levels of MDA (p = 0.01. Lung contusion due to blunt trauma significantly decreased SOD activities in rat lung tissue compared with group I (p = 0.01. SOD levels were significantly elevated in animals treated with CoQ10, Vitamin E, or Dxm compared with group II (p = 0.01. Conclusions In our study, CoQ10, vitamin C, vitamin E and Dxm had a protective effect on the biochemical and histopathological outcome of PC after experimental blunt thorax trauma.

Supplementing in the diet of lactating Holstein cows may naturally produce coenzyme Q10-enriched milk

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Gui-Seck Bae

2018-01-01

Full Text Available Objective To examine the effects of Rhodobacter sphaeroides (R. sphaeroides supplementation as a direct-fed microbial (DFM on rumen fermentation in dairy cows and on coenzyme Q10 (CoQ10 transition into milk, an in vitro rumen simulation batch culture and an in vivo dairy cow experiment were conducted. Methods The characteristics of in vitro ruminal fermentation were investigated using rumen fluids from six cannulated Holstein dairy cows at 2 h post-afternoon feeding. A control treatment was included in the experiments based on a typified total mixed ration (TMR for lactating dairy cows, which was identical to the one used in the in vivo study, plus R. sphaeroides at 0.1%, 0.3%, and 0.5% TMR dry matter. The in vivo study employed six ruminally cannulated lactating Holstein cows randomly allotted to either the control TMR (C-TMR treatment or to a diet supplemented with a 0.5% R. sphaeroides culture (S-TMR, dry matter basis ad libitum. The presence of R. sphaeroides was verified using denaturing gradient gel electrophoresis (DGGE applied to the bacterial samples obtained from the in vivo study. The concentration of CoQ10 in milk and in the supernatant from the in vitro study was determined using high performance liquid chromatography. Results The results of the in vitro batch culture and DGGE showed that the concentration of CoQ10 significantly increased after 2 h of R. sphaeroides supplementation above 0.1%. When supplemented to the diet of lactating cows at the level of 0.5%, R. sphaeroides did not present any adverse effect on dry matter intake and milk yield. However, the concentration of CoQ10 in milk dramatically increased, with treated cows producing 70.9% more CoQ10 than control cows. Conclusion The CoQ10 concentration in milk increased via the use of a novel DFM, and R. sphaeroides might be used for producing value-added milk and dairy products in the future.

Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial.

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Sanoobar, Meisam; Dehghan, Parvin; Khalili, Mohammad; Azimi, Amirreza; Seifar, Fatemeh

2016-01-01

Multiple sclerosis (MS) is the chronic inflammatory and demyelinating disorder of central nervous system which is accompanied with disability and negative life style changes such as fatigue and depression. The aim of this study is to investigate the effect of coenzyme Q10 (CoQ10) supplementation on fatigue and depression in patients with MS. We performed a randomized, double-blinded, placebo-controlled trial to determine the effect of CoQ10 supplement (500 mg/day) vs. placebo for 12 weeks. Fatigue symptoms were quantified by means of fatigue severity scale (FSS) and the Beck depression inventory (BDI) was used to assess depressive symptoms. A significant decrease of FSS was observed in CoQ10 group during the intervention (P = 0.001) and significant increase of FSS change was observed within placebo group (P = 0.001). Repeated measure analysis of variance showed a significant time-by-treatment interaction for FSS (baseline 41.5 ± 15.6 vs. endpoint 45 ± 13.6; F1,45 = 55.23, P multiple sclerosis.

Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast.

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Awad, Agape M; Venkataramanan, Srivats; Nag, Anish; Galivanche, Anoop Raj; Bradley, Michelle C; Neves, Lauren T; Douglass, Stephen; Clarke, Catherine F; Johnson, Tracy L

2017-09-08

Despite its relatively streamlined genome, there are many important examples of regulated RNA splicing in Saccharomyces cerevisiae Here, we report a role for the chromatin remodeler SWI/SNF in respiration, partially via the regulation of splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a mitochondrial phosphatase regulator of biosynthesis of coenzyme Q 6 (ubiquinone or CoQ 6 ) and a mitochondrial redox-active lipid essential for electron and proton transport in respiration. Increased splicing of PTC7 increases CoQ 6 levels. The increase in PTC7 splicing occurs at least in part due to down-regulation of ribosomal protein gene expression, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to otherwise poorly spliced transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7 represses CoQ 6 biosynthesis. Taken together, these findings uncover a link between Snf2 expression and the splicing of PTC7 and establish a previously unknown role for the SWI/SNF complex in the transition of yeast cells from fermentative to respiratory modes of metabolism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of coenzyme Q10 supplementation on the anthropometric variables, lipid profiles and liver enzymes in patients with non-alcoholic fatty liver disease

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Elnaz Jafarvand

2016-03-01

Full Text Available This randomized double-blind placebo-controlled trial was conducted on 41 patients with non-alcoholic fatty liver disease. Patients in intervention group received 100 mg/day coenzyme Q10 (CoQ10 for four weeks. There was a significant reduction in waist circumference and aspartate aminotransferase concentrations after CoQ10 supplementation (p<0.05. Dietary fiber was in negative correlation with change in serum alanine aminotransferase (ALT concentrations (r = -410, p = 0.04, and dietary fat intake was in positive relation with serum triglyceride (r = 463, p = 0.04 and in negative relation with serum high-density lipoprotein cholesterol (HDL-C (r = -533, p = 0.02 in CoQ10-treated group. CoQ10 supplement is able to reduce central obesity and improve liver function in non-alcoholic fatty liver disease. Dietary factors were also significant determinants of change in liver-specific enzyme ALT and lipid profile in these patients. Further trials with higher dose of CoQ10 and longer treatment periods are warranted to better clarify these findings.

Preparation and in vitro-in vivo evaluation of Witepsol H35 based self-nanoemulsifying drug delivery systems (SNEDDS) of coenzyme Q(10).

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Nepal, Pushp R; Han, Hyo-Kyung; Choi, Hoo-Kyun

2010-02-19

Coenzyme Q(10) (CoQ(10)) was formulated into self-nanoemulsifying drug delivery systems (SNEDDS) to overcome low bioavailability attributed to hydrophobic nature of the drug. Screening of oil phase, surfactants and co-surfactants were performed to select Witepsol H35, Solutol HS15 and Lauroglycol FCC, respectively. Ternary phase diagrams were drawn to identify nanoemulsifying region followed by optimization of SNEDDS formulation. The optimized formulation, CoQ(10), Witepsol H35, Solutol HS15 and Lauroglycol FCC in the weight ratio of 1:0.7:4:2, respectively, emulsified readily at 37 degrees C with mean emulsion droplet size of 32.4 nm. The stability test of the optimized formulation in pH 1.2 and 6.8 buffers confirmed no pH effect on emulsion droplet size. In vitro dissolution (emulsification) test and in vivo animal study of the formulation elucidated the complete emulsification of drug and improved oral bioavailability of poorly soluble CoQ(10). 2009 Elsevier B.V. All rights reserved.

Characterization of oat beta-glucan and coenzyme Q10-loaded beta-glucan powders generated by the pressurized gas-expanded liquid (PGX) technology.

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Liu, Nian; Couto, Ricardo; Seifried, Bernhard; Moquin, Paul; Delgado, Luis; Temelli, Feral

2018-04-01

The physicochemical properties of the oat beta-glucan powder (BG) and coenzyme Q10 (CoQ10)-loaded BG powder (L-BG) produced by the pressurized gas-expanded liquid (PGX) technology were studied. Helium ion microscope, differential scanning calorimeter, X-ray diffractometer, AutoSorb iQ and rheometer were used to determine the particle morphology, thermal properties, crystallinity, surface area and viscosity, respectively. Both BG (7.7μm) and L-BG (6.1μm) were produced as micrometer-scale particles, while CoQ10 nanoparticles (92nm) were adsorbed on the porous structure of L-BG. CoQ10 was successfully loaded onto BG using the PGX process via adsorptive precipitation mainly in its amorphous form. Viscosity of BG and L-BG solutions (0.15%, 0.2%, 0.3% w/v) displayed Newtonian behavior with increasing shear rate but decreased with temperature. Detailed characterization of the physicochemical properties of combination ingredients like L-BG will lead to the development of novel functional food and natural health product applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioavailability of four oral Coenzyme Q formulations in healthy volunteers

DEFF Research Database (Denmark)

Weis, M.; Mortensen, S.A.; Rassing, M.R.

1994-01-01

The bioavailability of four different Coenzyme Q (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatine capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatine capsules containing......Q (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o.administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile....

Beneficial effects of co-enzyme Q10 and rosiglitazone in fructose-induced metabolic syndrome in rats

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Suzan M. Mansour

2013-06-01

Full Text Available Increased fructose consumption is strongly associated with metabolic syndrome (MS. This study was performed to elucidate the role of co-enzyme Q10 (CoQ and/or rosiglitazone (Rosi in fructose induced MS. Four groups of rats (n = 8–10 were fed on fructose-enriched diet (FED for 16 weeks. One served as FED-control while the remaining groups were treated with CoQ (10 mg/kg/day, Rosi (4 mg/kg/day or their combination during the last 6 weeks. Another group was fed on normal laboratory chow (normal control. At the end of the experiment, blood samples were collected for estimation of markers related to MS. In addition, histological examination of liver, kidney and pancreas samples was done. Induction of the MS was associated with increased body weight gain (34% coupled with elevated levels of blood glucose (48%, insulin (86%, insulin resistance (270%, uric acid (69%, urea (155%, creatinine (129% and blood lipids with different degrees. Fructose-induced MS also reduced plasma catalase (62% and glutathione peroxidase (89% activities parallel to increased serum leptin and tumor necrosis factor-alpha (TNF-α levels. These changes were coupled by marked histological changes in the examined tissues. Treatment with CoQ or Rosi attenuated most of MS-induced changes. Besides, the combination of both agents further reduced blood glucose, total cholesterol, triglycerides and urea levels, as well as, normalized serum levels of leptin and TNF-α. In addition, combined therapy of both agents elevated HDL-cholesterol level and glutathione peroxidase activity. In conclusion, the present study proves the benefits of co-supplementation of CoQ and Rosi in a fructose-induced model of insulin resistance.

Water-Soluble Coenzyme Q10 Inhibits Nuclear Translocation of Apoptosis Inducing Factor and Cell Death Caused by Mitochondrial Complex I Inhibition

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Haining Li

2014-07-01

Full Text Available The objectives of the study were to explore the mechanism of rotenone-induced cell damage and to examine the protective effects of water-soluble Coenzyme Q10 (CoQ10 on the toxic effects of rotenone. Murine hippocampal HT22 cells were cultured with mitochondrial complex I inhibitor rotenone. Water-soluble CoQ10 was added to the culture media 3 h prior to the rotenone incubation. Cell viability was determined by alamar blue, reactive oxygen species (ROS production by dihydroethidine (DHE and mitochondrial membrane potential by tetramethyl rhodamine methyl ester (TMRM. Cytochrome c, caspase-9 and apoptosis-inducing factor (AIF were measured using Western blotting after 24 h rotenone incubation. Rotenone caused more than 50% of cell death, increased ROS production, AIF nuclear translocation and reduction in mitochondrial membrane potential, but failed to cause mitochondrial cytochrome c release and caspase-9 activation. Pretreatment with water-soluble CoQ10 enhanced cell viability, decreased ROS production, maintained mitochondrial membrane potential and prevented AIF nuclear translocation. The results suggest that rotenone activates a mitochondria-initiated, caspase-independent cell death pathway. Water-soluble CoQ10 reduces ROS accumulation, prevents the fall of mitochondrial membrane potential, and inhibits AIF translocation and subsequent cell death.

Comparative evaluation of coenzyme Q10-based gel and 0.8% hyaluronic acid gel in treatment of chronic periodontitis

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Varun Sharma

2016-01-01

Full Text Available Background: The anti-inflammatory and immune enhancing effects of coenzyme Q10 (CoQ10 and hyaluronic acid are well established in medical literature. The present study was undertaken to evaluate their role in chronic periodontitis. Materials and Methods: One hundred twenty sites in 24 patients with clinically confirmed periodontitis were included in the study. A split-mouth design was used for intrasulcular application of CoQ10as adjunct to scaling and root planing (SRP, 0.8% hyaluronic acid as adjunct to SRP and SRP alone. Clinical parameters such as plaque index (PI, gingival color change index (GCCI, Eastman interdental bleeding index (EIBI, pocket depth (PD, and clinical attachment level (CAL were recorded. All the clinical parameters PI, EIBI, GCCI, PD, and CAL were recorded at baseline before SRP. Only PI, EIBI, and GCCI were recorded at 1st and 2nd week. Twenty-one days post 2nd week, i.e., 6th week all the clinical parameters were recorded again. Results: Intragroup analysis of all the clinical parameters showed clinical significant results between baseline and 6th week. However, on intergroup analysis, the results were not significant. Conclusion: The local application of CoQ10and hyaluronic acid gel in conjunction with SRP may have a beneficial effect on periodontal health in patients with chronic periodontitis.

Potential administration of lipoic acid and coenzyme Q against ...

African Journals Online (AJOL)

Potential administration of lipoic acid and coenzyme Q against adipogensis: target for weight reduction. ... prevents its accumulation in visceral tissues. Further studies should be carried out to examine the mechanistic signals of these nutrients that helps in weight = management. Keywords: lipolysis, obesity, lipoic acid, Co-Q ...

Coenzyme Q10 quantification in muscle, fibroblasts and cerebrospinal fluid by liquid chromatography/tandem mass spectrometry using a novel deuterated internal standard.

Science.gov (United States)

Duberley, Kate E C; Hargreaves, Iain P; Chaiwatanasirikul, Korn-Anong; Heales, Simon J R; Land, John M; Rahman, Shamima; Mills, Kevin; Eaton, Simon

2013-05-15

Neurological dysfunction is common in primary coenzyme Q10 (2,3-dimethoxy, 5-methyl, 6-polyisoprene parabenzoquinone; CoQ10 ; ubiquinone) deficiencies, the most readily treatable subgroup of mitochondrial disorders. Therapeutic benefit from CoQ10 supplementation has also been noted in other neurodegenerative diseases. CoQ10 can be measured by high-performance liquid chromatography (HPLC) in plasma, muscle or leucocytes; however, there is no reliable method to quantify CoQ10 in cerebrospinal fluid (CSF). Additionally, many methods use CoQ9 , an endogenous ubiquinone in humans, as an internal standard. Deuterated CoQ10 (d6 -CoQ10 ) was synthesised by a novel, simple, method. Total CoQ10 was measured by liquid chromatography/tandem mass spectrometry (LC/MS/MS) using d6 -CoQ10 as internal standard and 5 mM methylamine as an ion-pairing reagent. Chromatography was performed using a Hypsersil GOLD C4 column (150 × 3 mm, 3 µm). CoQ10 levels were linear over a concentration range of 0-200 nM (R(2) = 0.9995). The lower limit of detection was 2 nM. The inter-assay coefficient of variation (CV) was 3.6% (10 nM) and 4.3% (20 nM), and intra-assay CV 3.4% (10 nM) and 3.6% (20 nM). Reference ranges were established for CoQ10 in CSF (5.7-8.7 nM; n = 17), fibroblasts (57.0-121.6 pmol/mg; n = 50) and muscle (187.3-430.1 pmol/mg; n = 15). Use of d6 -CoQ10 internal standard has enabled the development of a sensitive LC/MS/MS method to accurately determine total CoQ10 levels. Clinical applications of CSF CoQ10 determination include identification of patients with cerebral CoQ10 deficiency, and monitoring CSF CoQ10 levels following supplementation. Copyright © 2013 John Wiley & Sons, Ltd.

Paraquat induces oxidative stress, neuronal loss in substantia nigra region and Parkinsonism in adult rats: Neuroprotection and amelioration of symptoms by water-soluble formulation of Coenzyme Q10

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Sridhar TS

2009-07-01

Full Text Available Abstract Background Parkinson's disease, for which currently there is no cure, develops as a result of progressive loss of dopamine neurons in the brain; thus, identification of any potential therapeutic intervention for disease management is of a great importance. Results Here we report that prophylactic application of water-soluble formulation of coenzyme Q10 could effectively offset the effects of environmental neurotoxin paraquat, believed to be a contributing factor in the development of familial PD. In this study we utilized a model of paraquat-induced dopaminergic neurodegeneration in adult rats that received three weekly intra-peritoneal injections of the herbicide paraquat. Histological and biochemical analyses of rat brains revealed increased levels of oxidative stress markers and a loss of approximately 65% of dopamine neurons in the substantia nigra region. The paraquat-exposed rats also displayed impaired balancing skills on a slowly rotating drum (rotorod evidenced by their reduced spontaneity in gait performance. In contrast, paraquat exposed rats receiving a water-soluble formulation of coenzyme Q10 in their drinking water prior to and during the paraquat treatment neither developed neurodegeneration nor reduced rotorod performance and were indistinguishable from the control paraquat-untreated rats. Conclusion Our data confirmed that paraquat-induced neurotoxicity represents a convenient rat model of Parkinsonian neurodegeneration suitable for mechanistic and neuroprotective studies. This is the first preclinical evaluation of a water-soluble coenzyme Q10 formulation showing the evidence of prophylactic neuroprotection at clinically relevant doses.

Efficient Lewis Acid Ionic Liquid-Catalyzed Synthesis of the Key Intermediate of Coenzyme Q10 under Microwave Irradiation

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Thomas Efferth

2010-12-01

Full Text Available An efficient synthesis of a valuable intermediate of coenzyme Q10 by microwave-assisted Lewis acidic ionic liquid (IL-catalyzed Friedel-Crafts alkylation is reported. The acidity of six [Etpy]BF4-based ionic liquids was characterized by means of the FT-IR technique using acetonitrile as a molecular probe. The catalytic activities of these ionic liquids were correlated with their Lewis acidity. With increasing Lewis acid strength of the ionic liquids, their catalytic activity in the Friedel-Crafts reaction increased, except for [Etpy]BF4-AlCl3. The effects of the reaction system, the molar fraction of Lewis acid in the Lewis acid ILs and heating techniques were also investigated. Among the six Lewis acid ionic liquids tested [Etpy]BF4-ZnCl2 showed the best catalytic activity, with a yield of 89% after a very short reaction time (150 seconds. This procedure has the advantages of higher efficiency, better reusability of ILs, energy conservation and eco-friendliness. The method has practical value for preparation of CoQ10 on an industrial scale.

Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-β1 expression

International Nuclear Information System (INIS)

Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul; Han, Hyo-Kyung; Ryu, Chang Seon; Kim, Sang Kyum; Kwak, Mi Kyong; Kang, Keon Wook

2009-01-01

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-β1 (TGF-β1) mRNA and α-smooth muscle actin (α-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of α-SMA and TGF-β1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of α-SMA and TGF-β1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-β1 expression via Nrf2/ARE activation.

The effects of coenzyme Q10 treatment on maternally inherited diabetes mellitus and deafness, and mitochondrial DNA 3243 (A to G) mutation.

Science.gov (United States)

Suzuki, S; Hinokio, Y; Ohtomo, M; Hirai, M; Hirai, A; Chiba, M; Kasuga, S; Satoh, Y; Akai, H; Toyota, T

1998-05-01

The characteristic clinical features of diabetes mellitus with mitochondrial DNA (mtDNA) 3243(A-G) mutation are progressive insulin secretory defect, neurosensory deafness and maternal inheritance, referred to as maternally inherited diabetes mellitus and deafness (MIDD). A treatment for MIDD to improve insulin secretory defects and reduce deafness has not been established. The effects of coenzyme Q10 (CoQ10) treatment on insulin secretory response, hearing capacity and clinical symptoms of MIDD were investigated. 28 MIDD patients (CoQ10-DM), 7 mutant subjects with impaired glucose tolerance (IGT), and 15 mutant subjects with normal glucose tolerance (NGT) were treated daily with oral administration of 150 mg of CoQ10 for 3 years. Insulin secretory response, blood lactate after exercise, hearing capacity and other laboratory examinations were investigated every year. In the same way we evaluated 16 MIDD patients (control-DM), 5 mutant IGT and 5 mutant NGT subjects in yearly examinations. The insulin secretory response assessed by glucagon-induced C-peptide secretion and 24 h urinary C-peptide excretion after 3 years in the CoQ10-DM group was significantly higher than that in the control-DM group. CoQ10 therapy prevented progressive hearing loss and improved blood lactate after exercise in the MIDD patients. CoQ10 treatment did not affect the diabetic complications or other clinical symptoms of MIDD patients. CoQ10 treatment did not affect the insulin secretory capacity of the mutant IGT and NGT subjects. There were no side effects during therapy. This is the first report demonstrating the therapeutic usefulness of CoQ10 on MIDD.

Altered bacterial metabolism, not coenzyme Q content, is responsible for the lifespan extension in Caenorhabditis elegans fed an Escherichia coli diet lacking coenzyme Q.

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Saiki, Ryoichi; Lunceford, Adam L; Bixler, Tarra; Dang, Peter; Lee, Wendy; Furukawa, Satoru; Larsen, Pamela L; Clarke, Catherine F

2008-06-01

Coenzyme Q(n) is a fully substituted benzoquinone containing a polyisoprene tail of distinct numbers (n) of isoprene groups. Caenorhabditis elegans fed Escherichia coli devoid of Q(8) have a significant lifespan extension when compared to C. elegans fed a standard 'Q-replete'E. coli diet. Here we examine possible mechanisms for the lifespan extension caused by the Q-less E. coli diet. A bioassay for Q uptake shows that a water-soluble formulation of Q(10) is effectively taken up by both clk-1 mutant and wild-type nematodes, but does not reverse lifespan extension mediated by the Q-less E. coli diet, indicating that lifespan extension is not due to the absence of dietary Q per se. The enhanced longevity mediated by the Q-less E. coli diet cannot be attributed to dietary restriction, different Qn isoforms, reduced pathogenesis or slowed growth of the Q-less E. coli, and in fact requires E. coli viability. Q-less E. coli have defects in respiratory metabolism. C. elegans fed Q-replete E. coli mutants with similarly impaired respiratory metabolism due to defects in complex V also show a pronounced lifespan extension, although not as dramatic as those fed the respiratory deficient Q-less E. coli diet. The data suggest that feeding respiratory incompetent E. coli, whether Q-less or Q-replete, produces a robust life extension in wild-type C. elegans. We believe that the fermentation-based metabolism of the E. coli diet is an important parameter of C. elegans longevity.

The effect of short-term coenzyme Q10 supplementation and pre-cooling strategy on cardiac damage markers in elite swimmers.

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Emami, Ali; Tofighi, Asghar; Asri-Rezaei, Siamak; Bazargani-Gilani, Behnaz

2018-02-01

Strenuous physical exercise and hyperthermia may paradoxically induce oxidative stress and adverse effects on myocardial function. The purpose of this study was to investigate the effect of 14-d coenzyme Q10 (CoQ10) supplementation and pre-cooling on serum creatine kinase-MB (CK-MB), cardiac Troponin I (cTnI), myoglobin (Mb), lactate dehydrogenase (LD), total antioxidant capacity (TAC), lipid peroxidation (LPO) and CoQ10 concentration in elite swimmers. In total, thirty-six healthy males (mean age 17 (sd 1) years) were randomly selected and divided into four groups of supplementation, supplementation with pre-cooling, pre-cooling and control. During an eighteen-session protocol in the morning and evening, subjects attended speed and endurance swimming training sessions for 5 km in each session. Blood sampling was done before (two stages) and after (two stages) administration of CoQ10 and pre-cooling. ANCOVA and repeated measurement tests with Bonferroni post hoc test were used for the statistical analysis of the data. There was no significant statistical difference among groups for the levels of CK-MB, cTnI, Mb, LD, TAC, LPO and CoQ10 at the presampling (stages 1 and 2) (P>0·05). However, pre-cooling and control groups show a significant increase in the levels of CK-MB, cTnI, Mb, LD and LPO compared with the supplementation and supplementation with pre-cooling groups in the post-sampling (stages 1 and 2) (Pcompetition phase. Meanwhile, the pre-cooling strategy individually has no desired effect on the levels of CK-MB, cTnI, Mb, LD, LPO, TAC and CoQ10.

Effects of Coenzyme Q10 and Vitamin C on Growth Performance and Blood Components in Broiler Chickens under Heat Stress

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Raeisi-Zeydabad S

2017-10-01

Full Text Available This experiment was carried out to study the effects of Coenzyme Q10 (CoQ10 and vitamin C (VC on growth performance and blood biochemistry in broiler chickens under heat stress conditions. One of three levels of CoQ10 (0, 20, and 40 mg/kg of diet and one of two levels of VC (0 and 250 mg/kg of diet were supplemented to diets of chicks (from 1-42 d of age in a 3 × 2 factorial arrangement. Each dietary treatment had four replicate pens (10 chicks/pen. In order to create chronic heat stress, the house temperature was set at an ambient temperature of 35±2°C for 8 hrs daily (09:00 to 17:00 between 25-42 d of age. Feed intake, body weight gain (BWG, and feed to gain ratio (F:G were recorded at d 10, 25 and 42. At the end of experiment, two chicks/pen were randomly selected to assess blood components. CoQ10 supplementation improved BWG and F:G during 11-25 days, 26-42 days, and the whole period of the experiment (P < 0.05, while VC supplementation improved BWG and F:G only during 11-25 d of age. Blood glucose, cholesterol and triglycerides concentrations were reduced (P < 0.05 by addition of CoQ10 to the diet. Both Supplementation of CoQ10 and VC together lowered heterophil (H count but increased lymphocyte (L count, thereby reducing H/L ratio (P < 0.05. Serum concentrations of corticosterone and T4 were positively affected by dietary supplementation of CoQ10 (P < 0.05, but no differences were obtained with addition of VC to the diet. In conclusion, our observations demonstrated that dietary supplementation of 40 mg/kg CoQ10 or 250 mg/kg VC improves the growth performance of broiler chickens under the heat stress.

Age-Related Loss in Bone Mineral Density of Rats Fed Lifelong on a Fish Oil-Based Diet Is Avoided by Coenzyme Q10 Addition

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Alfonso Varela-López

2017-02-01

Full Text Available During aging, bone mass declines increasing osteoporosis and fracture risks. Oxidative stress has been related to this bone loss, making dietary compounds with antioxidant properties a promising weapon. Male Wistar rats were maintained for 6 or 24 months on diets with fish oil as unique fat source, supplemented or not with coenzyme Q10 (CoQ10, to evaluate the potential of adding this molecule to the n-3 polyunsaturated fatty acid (n-3 PUFA-based diet for bone mineral density (BMD preservation. BMD was evaluated in the femur. Serum osteocalcin, osteopontin, receptor activator of nuclear factor-κB ligand, ostroprotegerin, parathyroid hormone, urinary F2-isoprostanes, and lymphocytes DNA strand breaks were also measured. BMD was lower in aged rats fed a diet without CoQ10 respect than their younger counterparts, whereas older animals receiving CoQ10 showed the highest BMD. F2-isoprostanes and DNA strand breaks showed that oxidative stress was higher during aging. Supplementation with CoQ10 prevented oxidative damage to lipid and DNA, in young and old animals, respectively. Reduced oxidative stress associated to CoQ10 supplementation of this n-3 PUFA-rich diet might explain the higher BMD found in aged rats in this group of animals.

Coenzyme Q supplementation in pulmonary arterial hypertension

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Jacqueline Sharp

2014-01-01

Full Text Available Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH. Because coenzyme Q (CoQ is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8 in comparison to healthy controls (N=7, at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement.

Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens

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Johansson, Peter; Aaseth, Jan; Alexander, Jan; Brismar, Kerstin

2017-01-01

Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P>0.0001), IGF-1 SD score (F = 29; PIGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed. PMID:28609475

Therapeutic effects of coenzyme Q10 on dilated cardiomyopathy. Assessment by {sup 123}I-BMIPP myocardial single photon emission computed tomography (SPECT). A multicenter trial in Osaka University Medical School Group

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Nishimura, Tsunehiko; Hori, Masatsugu [Osaka Univ. (Japan). Faculty of Medicine

1996-01-01

To evaluate therapeutic effects of Coenzyme Q10 (CoQ10), 15 patients with dilated cardiomyopathy were investigated by {sup 123}I-BMIPP myocardial single photon emission computed tomography (SPECT). The BMIPP defect score was determined semiquantitatively by using representative short and long axial SPECT images. Mean BMIPP defect score with CoQ10 treatment was significantly low, 7.7{+-}6.1 compared to 12.7{+-}7.4 without CoQ10 treatment. On the other hand, in 8 patients of dilated cardiomyopathy, % fractional shortening using echocardiography was not different before and after CoQ10 treatment. In conclusion, {sup 123}I-BMIPP myocardial SPECT was proved to be sensitive to evaluate the therapeutic effects of CoQ10, which improve myocardial mitochondrial function, in the cases of dilated cardiomyopathy. (author).

Efficacy of eyedrops containing cross-linked hyaluronic acid and coenzyme Q10 in treating patients with mild to moderate dry eye.

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Postorino, Elisa I; Rania, Laura; Aragona, Emanuela; Mannucci, Carmen; Alibrandi, Angela; Calapai, Gioacchino; Puzzolo, Domenico; Aragona, Pasquale

2018-01-01

Dry eye disease (DED) is a common condition causing substantial burden. A randomized, controlled, single-masked study was performed in 40 patients with mild to moderate DED to evaluate the efficacy and safety of a collyrium based on crosslinked hyaluronic acid (XLHA) with coenzyme Q10 (CoQ10). Enrolled subjects were divided into 2 groups: group A, treated with XLHA + CoQ10; and group B, treated with hyaluronic acid (HA). Eyedrops were administered 4 times daily for 3 months. The Ocular Surface Disease Index (OSDI) questionnaire, tear break-up time (TBUT), corneal and conjunctival staining, and meibomian gland assessment (MGD) were evaluated; furthermore, corneal aesthesiometry, in vivo corneal confocal microscopy, visual acuity, intraocular pressure (IOP), and fundus examination were performed. At the end of treatment, OSDI score significantly decreased in groups A and B (p<0.01 and p<0.05, respectively); the decrease was significantly higher in group A. Corneal staining decreased in both groups, with lower scores in group A. The MGD was significantly ameliorated in group A patients. No differences were found for corneal aesthesiometry or TBUT. Epithelial cell reflectivity was significantly reduced only in group A. For keratocytes and stromal matrix parameters, there was a significant improvement in group A. No changes were found for visual acuity, IOP, or fundus examination. The XLHA + CoQ10 treatment showed greater effectiveness in DED compared to HA alone, probably due to the longer permanency on ocular surface and the antioxidant activity of CoQ10. Therefore, XLHA + CoQ10 eyedrops could represent a new possibility in dry eye treatment.

Regulation of the oxidative balance with coenzyme Q10 sensitizes human glioblastoma cells to radiation and temozolomide.

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Frontiñán-Rubio, Javier; Santiago-Mora, Raquel María; Nieva-Velasco, Consuelo María; Ferrín, Gustavo; Martínez-González, Alicia; Gómez, María Victoria; Moreno, María; Ariza, Julia; Lozano, Eva; Arjona-Gutiérrez, Jacinto; Gil-Agudo, Antonio; De la Mata, Manuel; Pesic, Milica; Peinado, Juan Ramón; Villalba, José M; Pérez-Romasanta, Luis; Pérez-García, Víctor M; Alcaín, Francisco J; Durán-Prado, Mario

2018-05-18

To investigate how the modulation of the oxidative balance affects cytotoxic therapies in glioblastoma, in vitro. Human glioblastoma U251 and T98 cells and normal astrocytes C8D1A were loaded with coenzyme Q10 (CoQ). Mitochondrial superoxide ion (O 2 - ) and H 2 O 2 were measured by fluorescence microscopy. OXPHOS performance was assessed in U251 cells with an oxytherm Clark-type electrode. Radio- and chemotherapy cytotoxicity was assessed by immunostaining of γH2AX (24 h), annexin V and nuclei morphology, at short (72 h) and long (15 d) time. Hif-1α, SOD1, SOD2 and NQO1 were determined by immunolabeling. Catalase activity was measured by classic enzymatic assay. Glutathione levels and total antioxidant capacity were quantified using commercial kits. CoQ did not affect oxygen consumption but reduced the level of O 2 - and H 2 O 2 while shifted to a pro-oxidant cell status mainly due to a decrease in catalase activity and SOD2 level. Hif-1α was dampened, echoed by a decrease lactate and several key metabolites involved in glutathione synthesis. CoQ-treated cells were twofold more sensitive than control to radiation-induced DNA damage and apoptosis in short and long-term clonogenic assays, potentiating TMZ-induced cytotoxicity, without affecting non-transformed astrocytes. CoQ acts as sensitizer for cytotoxic therapies, disarming GBM cells, but not normal astrocytes, against further pro-oxidant injuries, being potentially useful in clinical practice for this fatal pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatoprotective effect of taurine and coenzyme Q10 and their ...

African Journals Online (AJOL)

CoQ10) for mitigation of acrylamide- induced oxidative damage. . Method: Acrylamide (AA), TA and CoQ10 were administered orally to rats for 2 and 4 weeks. Sixty albino rats of either sex weighing 200 ± 5 were randomly divided into five groups; ...

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy.

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Latkovskis, Gustavs; Saripo, Vita; Sokolova, Emma; Upite, Dana; Vanaga, Ilona; Kletnieks, Ugis; Erglis, Andrejs

2016-01-01

Statin-induced myopathy (SIM) has been partially attributed to deficiency of dolichol and coenzyme Q10 (CoQ10). We aimed to test the safety and efficacy of plant polyprenols in combination with CoQ10 for alleviation of SIM. In an open-label, one-center prospective pilot study patients with SIM received conifer-tree needle polyprenols (4mg/day) and CoQ10 (100mg/day) for 8 weeks. Symptoms and safety were evaluated according to symptom severity score (0-10), creatine kinase (CK) levels, exercise test, dynamometry, complete blood count, clinical biochemistry and electrocardiography. Of the 14 patients, 11 completed the study per protocol. Two patients withdrew consent due to travels abroad, and it was discontinued for one patient with stage 3 chronic kidney disease due to asymptomatic elevations of liver enzymes at week 4. No safety parameters changed significantly in per protocol group. Non-significant increase of CK levels was observed (P=0.231). Muscle pain (n=10) and weakness (n=7) scores improved significantly (PMuscle pain completely disappeared in 2 patients, weakness resolved in 3 patients and cramps disappeared in two patients. Four patients assessed improvement strong enough to consider increase of statin dose. No changes were observed in exercise test or dynamometry. Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols. Copyright © 2016 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

DEFF Research Database (Denmark)

Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

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Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

2017-03-01

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

Prophylactic role of combined treatment with coenzyme Q10 and vitamin E against radiation injury in male rats

International Nuclear Information System (INIS)

Hussien, E.M.; Darwish, M.M.; Ali, S.E.

2007-01-01

The present work aims at investigating effects of whole body gamma irradiation of male albino rats at successive fractionated dose levels up to 8 Gy and the possible protection or curative control of these effects through the oral administration of Coenzyme Q10 (Co Q10) (200 mg/ kg body wt) and vitamin E (100 mg/ kg body wt) injected i.p 24 h before exposure of animals to each increment of gamma irradiation. The parameters of the study have been combined haematological values, including evaluation of different blood cells, erythrocyte counts (RBC), haemoglobin concentration (Hb), haematocrit percentage (Ht) and leucocyte counts (WBC), as well as certain serum biochemical parameters including transaminases AST and ALT) and alkaline phosphatase (ALP) activities known to be related to liver functional status. Besides body and particular organs, wt as well as serum Na + and K + levels have been also evaluated. The results obtained confirmed in general, significant decrease in whole body and organs wt, haematological disorders in form of lowering of RBC, WBC, Hb and Ht, as well as elevated AST, ALT and ALP activities in irradiated rats in both studied time intervals. A significant increase in the level of K + associated with a decrease in the level of Na + was also recorded in the serum of irradiated rats. As simultaneous administration of Co Q10 and vitamin E prior to irradiation prevented pathological changes of analyzed parameters, the results of this study confirmed efficient protection with use of these antioxidants against the health hazards induced by gamma radiation exposure

Treatment of CoQ(10 deficient fibroblasts with ubiquinone, CoQ analogs, and vitamin C: time- and compound-dependent effects.

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Luis C López

2010-07-01

Full Text Available Coenzyme Q(10 (CoQ(10 and its analogs are used therapeutically by virtue of their functions as electron carriers, antioxidant compounds, or both. However, published studies suggest that different ubiquinone analogs may produce divergent effects on oxidative phosphorylation and oxidative stress.To test these concepts, we have evaluated the effects of CoQ(10, coenzyme Q(2 (CoQ(2, idebenone, and vitamin C on bioenergetics and oxidative stress in human skin fibroblasts with primary CoQ(10 deficiency. A final concentration of 5 microM of each compound was chosen to approximate the plasma concentration of CoQ(10 of patients treated with oral ubiquinone. CoQ(10 supplementation for one week but not for 24 hours doubled ATP levels and ATP/ADP ratio in CoQ(10 deficient fibroblasts therein normalizing the bioenergetics status of the cells. Other compounds did not affect cellular bioenergetics. In COQ2 mutant fibroblasts, increased superoxide anion production and oxidative stress-induced cell death were normalized by all supplements.THESE RESULTS INDICATE THAT: 1 pharmacokinetics of CoQ(10 in reaching the mitochondrial respiratory chain is delayed; 2 short-tail ubiquinone analogs cannot replace CoQ(10 in the mitochondrial respiratory chain under conditions of CoQ(10 deficiency; and 3 oxidative stress and cell death can be counteracted by administration of lipophilic or hydrophilic antioxidants. The results of our in vitro experiments suggest that primary CoQ(10 deficiencies should be treated with CoQ(10 supplementation but not with short-tail ubiquinone analogs, such as idebenone or CoQ(2. Complementary administration of antioxidants with high bioavailability should be considered if oxidative stress is present.

Significance of Ubiad1 for Epidermal Keratinocytes Involves More Than CoQ10 Synthesis: Implications for Skin Aging

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Florian Labarrade

2018-01-01

Full Text Available The significance of Coenzyme Q10 (CoQ10 as an anti-oxidant barrier of the skin, as well as a key component in anti-aging strategies for skin care products, has been firmly established. Biosynthesis of CoQ10 in the mitochondria is well known, but there is only limited information on the non-mitochondrial synthesis of CoQ10 in the skin. Recent findings in zebrafish identified that a tumor suppressor, Ubiad1, is also a key enzyme in the non-mitochondrial synthesis of CoQ10. The purpose of this study was to investigate expression of Ubiad1 in human skin, and its implication in the skin’s cutaneous response to oxidative stress. We observed Ubiad1 localization in the epidermis, particularly a subcellular localization in the Golgi apparatus. Ubiad1 modulation by a pentapeptide was associated with an observed reduction in ROS/RNS stresses (−44%/−19% respectively, lipid peroxidation (−25% and preservation of membrane fluidity under stress conditions. Electron microscopy of keratinocytes revealed a significant degree of stimulation of the Golgi complex, as well as significantly improved mitochondrial morphology. Given the importance of CoQ10 in mitigating the visible signs of skin aging, our findings identify Ubiad1 as an essential component of the defensive barriers of the epidermis.

Pretreatment with coenzyme Q10 improves ovarian response and embryo quality in low-prognosis young women with decreased ovarian reserve: a randomized controlled trial.

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Xu, Yangying; Nisenblat, Victoria; Lu, Cuiling; Li, Rong; Qiao, Jie; Zhen, Xiumei; Wang, Shuyu

2018-03-27

Management of women with reduced ovarian reserve or poor ovarian response (POR) to stimulation is one of the major challenges in reproductive medicine. The primary causes of POR remain elusive and oxidative stress was proposed as one of the important contributors. It has been suggested that focus on the specific subpopulations within heterogeneous group of poor responders could assist in evaluating optimal management strategies for these patients. This study investigated the effect of anti-oxidant treatment with coenzyme Q10 (CoQ10) on ovarian response and embryo quality in young low-prognosis patients with POR. This prospective, randomized controlled study included 186 consecutive patients with POR stratified according to the POSEIDON classification group 3 (age reserve parameters). The participants were randomized to the CoQ10 pre-treatment for 60 days preceding IVF-ICSI cycle or no pre-treatment. The number of high quality embryos was a primary outcome measure. A total of 169 participants were evaluated (76 treated with CoQ10 and 93 controls); 17 women were excluded due to low compliance with CoQ10 administration. The baseline demographic and clinical characteristics were comparable between the groups. CoQ10 pretreatment resulted in significantly lower gonadotrophin requirements and higher peak E2 levels. Women in CoQ10 group had increased number of retrieved oocytes (4, IQR 2-5), higher fertilization rate (67.49%) and more high-quality embryos (1, IQR 0-2); p reserve in IVF-ICSI cycles. Further work is required to determine whether there is an effect on clinical treatment endpoints.

Microglial inhibitory mechanism of Coenzyme Q10 against Aβ (1-42 induced cognitive dysfunctions: possible behavioral, biochemical, cellular and histopathological alterations

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Arti eSingh

2015-11-01

Full Text Available Rationale: Alzheimer’s disease (AD is a debilitating disease with complex pathophysiology. Amyloid beta (Aβ (1-42 is a reliable model of AD that recapitulates many aspects of human AD. Objective: The present study has been designed to investigate the neuroprotective potential of Coenzyme Q10 (CoQ10 and its modulation with minocycline (microglial inhibitor against Aβ (1-42 induced cognitive dysfunction in rats. Method: Intrahippocampal (i.h. Aβ (1-42 (1µg/µl; 4µl/site were administered followed by drug treatment with galantamine (2 mg/kg, CoQ10 (20 and 40 mg/kg, minocycline (50 and 100 mg/kg and their combinations for a period of 21 days. Various neurobehavioral parameters followed by biochemical, acetylcholinesterase (AChE level, proinflammatory markers (TNF-α, mitochondrial respiratory enzyme complexes (I-IV and histopathological examinations were assessed.Results: Aβ (1-42 administration significantly impaired cognitive performance in Morris water maze (MWM performance test, causes oxidative stress, raised AChE level, caused neuroinflammation, mitochondrial dysfunction and histopathological alterations as compared to sham treatment. Treatment with CoQ10 (20 and 40 mg/kg and minocycline (50 and 100 mg/kg alone for 21days significantly improved cognitive performance as evidenced by reduced transfer latency and increased time spent in target quadrant (TSTQ, reduced AChE activity, oxidative damage (reduced LPO, nitrite level and restored SOD, catalase and GHS levels, TNF-α level, restored mitochondrial respiratory enzyme complex (I, II, III, IV activities and histopathological alterations as compared to control (Aβ (1-42 treated animals group. Further, combination of minocycline (50 and 100 mg/kg with CoQ10 (20 and 40 mg/kg significantly modulate the protective effect of CoQ10 as compared to their effect alone. Conclusion: The present study suggests that the neuroprotective effect of CoQ10 could be due to its microglia inhibitory

Functional conservation of coenzyme Q biosynthetic genes among yeasts, plants, and humans.

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Kazuhiro Hayashi

Full Text Available Coenzyme Q (CoQ is an essential factor for aerobic growth and oxidative phosphorylation in the electron transport system. The biosynthetic pathway for CoQ has been proposed mainly from biochemical and genetic analyses of Escherichia coli and Saccharomyces cerevisiae; however, the biosynthetic pathway in higher eukaryotes has been explored in only a limited number of studies. We previously reported the roles of several genes involved in CoQ synthesis in the fission yeast Schizosaccharomyces pombe. Here, we expand these findings by identifying ten genes (dps1, dlp1, ppt1, and coq3-9 that are required for CoQ synthesis. CoQ10-deficient S. pombe coq deletion strains were generated and characterized. All mutant fission yeast strains were sensitive to oxidative stress, produced a large amount of sulfide, required an antioxidant to grow on minimal medium, and did not survive at the stationary phase. To compare the biosynthetic pathway of CoQ in fission yeast with that in higher eukaryotes, the ability of CoQ biosynthetic genes from humans and plants (Arabidopsis thaliana to functionally complement the S. pombe coq deletion strains was determined. With the exception of COQ9, expression of all other human and plant COQ genes recovered CoQ10 production by the fission yeast coq deletion strains, although the addition of a mitochondrial targeting sequence was required for human COQ3 and COQ7, as well as A. thaliana COQ6. In summary, this study describes the functional conservation of CoQ biosynthetic genes between yeasts, humans, and plants.

Photoionization of oxidized coenzyme Q in microemulsion: laser flash photolysis study in biomembrane-like system.

Science.gov (United States)

Li, Kun; Wang, Mei; Wang, Jin; Zhu, Rongrong; Sun, Dongmei; Sun, Xiaoyu; Wang, Shi-Long

2013-01-01

Photoexcitation to generate triplet state has been proved to be the main photoreaction in homogeneous system for many benzoquinone derivatives, including oxidized coenzyme Q (CoQ) and its analogs. In the present study, microemulsion of CoQ, a heterogeneous system, is employed to mimic the distribution of CoQ in biomembrane. The photochemistry of CoQ(10) in microemulsion and cyclohexane is investigated and compared using laser flash photolysis and results show that CoQ(10) undergoes photoionization via a monophotonic process to generate radical cation of CoQ(10) in microemulsion and photoexcitation to generate excited triplet state in cyclohexane. Meanwhile, photoreactions of duroquinone (DQ) and CoQ(0) in microemulsion are also investigated to analyze the influence of molecular structure on the photochemistry of benzoquinone derivatives in microemulsion. Results suggest that photoexcitation, which is followed by excited state-involved hydrogen-abstraction reaction, is the main photoreaction for DQ and CoQ(0) in microemulsion. However, photoexcited CoQ(0) also leads to the formation of hydrated electrons. The isoprenoid side chain-involved high resonance stabilization is proposed to explain the difference in photoreactions of CoQ(0) and CoQ(10) in microemulsion. Considering that microemulsion is close to biomembrane system, its photoionization in microemulsion may be helpful to understand the real photochemistry of biological quinones in biomembrane system. © 2012 Tongji University. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Pharmacological Chaperones and Coenzyme Q10 Treatment Improves Mutant β-Glucocerebrosidase Activity and Mitochondrial Function in Neuronopathic Forms of Gaucher Disease

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de la Mata, Mario; Cotán, David; Oropesa-Ávila, Manuel; Garrido-Maraver, Juan; Cordero, Mario D.; Villanueva Paz, Marina; Delgado Pavón, Ana; Alcocer-Gómez, Elizabet; de Lavera, Isabel; Ybot-González, Patricia; Paula Zaderenko, Ana; Ortiz Mellet, Carmen; Fernández, José M. García; Sánchez-Alcázar, José A.

2015-01-01

Gaucher disease (GD) is caused by mutations in the GBA1 gene, which encodes lysosomal β-glucocerebrosidase. Homozygosity for the L444P mutation in GBA1 is associated with high risk of neurological manifestations which are not improved by enzyme replacement therapy. Alternatively, pharmacological chaperones (PCs) capable of restoring the correct folding and trafficking of the mutant enzyme represent promising alternative therapies.Here, we report on how the L444P mutation affects mitochondrial function in primary fibroblast derived from GD patients. Mitochondrial dysfunction was associated with reduced mitochondrial membrane potential, increased reactive oxygen species (ROS), mitophagy activation and impaired autophagic flux.Both abnormalities, mitochondrial dysfunction and deficient β-glucocerebrosidase activity, were partially restored by supplementation with coenzyme Q10 (CoQ) or a L-idonojirimycin derivative, N-[N’-(4-adamantan-1-ylcarboxamidobutyl)thiocarbamoyl]-1,6-anhydro-L-idonojirimycin (NAdBT-AIJ), and more markedly by the combination of both treatments. These data suggest that targeting both mitochondria function by CoQ and protein misfolding by PCs can be promising therapies in neurological forms of GD. PMID:26045184

The effects of coenzyme Q10 supplementation on cardiometabolic markers in overweight type 2 diabetic patients with stable myocardial infarction: A randomized, double-blind, placebo-controlled trial

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Seyyed Mehdi Mirhashemi

2016-09-01

Full Text Available BACKGROUND: Limited data are present that have assessed the effects of coenzyme Q10 (CoQ10 intake on cardiometabolic markers in type 2 diabetic patients with coronary heart disease (CHD. This study was done to determine the effects of CoQ10 administration on cardiometabolic markers in overweight diabetic patients with stable myocardial infarction. METHODS: This randomized double-blind placebo-controlled clinical trial was done among 60 diabetic patients with CHD aged 45-75 years old. Subjects were randomly allocated into two groups to receive either 100 mg/day CoQ10 supplements (n = 30 or placebo (n = 30 for 8 weeks. RESULTS: Compared with the placebo, CoQ10 intake led to a significant reduction in serum interleukin 6 (IL-6 (-1.7 ± 1.6 vs. 0.8 ± 1.7 ng/l, P < 0.001 and protein carbonyl (PCO levels (-0.2 ± 0.3 vs. 0.1 ± 0.2 nmol/mg protein, P < 0.001. Supplementation with CoQ10 did not affect serum lipoprotein(a, advanced glycation end-products and thiol concentrations compared with the placebo. CONCLUSION: Overall, this study indicated that CoQ10 intake after 8 weeks among diabetic patients with the stable CHD had beneficial effects on serum IL-6 and PCO levels, but did not alter other cardiometabolic markers.  

Low-cost and disposable sensors for the simultaneous determination of coenzyme Q10 and α-lipoic acid using manganese (IV) oxide-modified screen-printed graphene electrodes.

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Charoenkitamorn, Kanokwan; Chaiyo, Sudkate; Chailapakul, Orawon; Siangproh, Weena

2018-04-03

In this work, for the first time, manganese (IV) oxide-modified screen-printed graphene electrodes (MnO 2 /SPGEs) were developed for the simultaneous electrochemical detection of coenzyme Q10 (CoQ10) and α-lipoic acid (ALA). This sensor exhibits attractive benefits such as simplicity, low production costs, and disposability. Cyclic voltammetry (CV) was used to characterize the electrochemical behavior of the analyte and investigate the capacitance and electroactive surface area of the unmodified and modified electrode surfaces. The electrochemical behavior of CoQ10 and ALA on MnO 2 /SPGEs was also discussed. Additionally, square wave anodic stripping voltammetry (SWASV) was used for the quantitative determination of CoQ10 and ALA. Under optimal conditions, the obtained signals are linear in the concentration range from 2.0 to 75.0 μg mL -1 for CoQ10 and 0.3-25.0 μg mL -1 for ALA. The low limits of detection (LODs) were found to be 0.56 μg mL -1 and 0.088 μg mL -1 for CoQ10 and ALA, respectively. Moreover, we demonstrated the utility and applicability of the MnO 2 /SPGE sensor through simultaneous measurements of CoQ10 and ALA in dietary supplements. The sensor provides high accuracy measurements, exhibiting its high potential for practical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Targeting Oxidative Stress, Cytokines and Serotonin Interactions Via Indoleamine 2, 3 Dioxygenase by Coenzyme Q10: Role in Suppressing Depressive Like Behavior in Rats.

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Abuelezz, Sally A; Hendawy, Nevien; Magdy, Yosra

2017-06-01

Depression is a major health problem in which oxidative stress and inflammation are inextricably connected in its pathophysiology. Coenzyme Q10 (CoQ10) is an important anti-oxidant compound with anti-inflammatory and neuro-protective properties. This study was designed to investigate the hypothesis that CoQ10 by its anti-oxidant and anti-inflammatory potentials can alleviate depressive- like behavior by restoring the balance of the tryptophan catabolites kynurenine/serotonin toward the serotonin pathway by down-regulation of hippocampal indoleamine 2,3-dioxygenase 1 (IDO-1). Depressive-like behavior was induced by chronic unpredictable mild stress (CUMS) protocol including food or water deprivation, cage tilting, reversed light cycle etc. Male Wistar rats were randomly divided into five groups; Control, CUMS, CUMS and CoQ10 (50,100 and 200 mg/kg/day i.p. respectively) groups. CoQ10 effects on different behavioral and biochemical tests were analyzed. CoQ10 showed significant antidepressant efficacy, as evidenced by significantly decreased stress induced changes to forced swimming challenge and open field test, as well as attenuating raised corticosterone level and adrenal glands weight. The anti-oxidant effect of CoQ10 was exhibited by its ability to significantly reduce hippocampal elevated malondialdehyde and 4-hydroxynonenal levels and elevate the reduced glutathione and catalase levels. CoQ10 significantly reduced different pro-inflammatory cytokines levels including interleukin (IL)-1β, IL-2, IL-6 and tumor necrosis factor-α. It suppressed hippocampal IDO-1 and subsequent production of kynurenine and enhanced the hippocampal contents of tryptophan and serotonin. Immunohistochemical analysis revealed that CoQ10 was able to attenuate the elevated microglial CD68 and elevate the astrocyte glial fibrillary acidic protein compared to CUMS group. CoQ10 exhibited antidepressant-like effects on rats exposed to CUMS. This could be attributed to its ability to reduce

Nedsat koenzym Q10 kan være årsag til statinassocieret myopati

DEFF Research Database (Denmark)

Nielsen, Mette Lundgren; Pareek, Manan; Henriksen, Jan Erik

2011-01-01

Statin treatment can cause muscular side effects. It has been suggested that the mechanism is reduced synthesis of coenzyme Q10 (coQ10) and a subsequent dysfunction of the respiratory chain. A literature review resulted in insufficient evidence supporting this theory. It is uncertain whether...... intramuscular levels of coQ10 and mitochondrial function are affected by statin therapy and whether the symptoms of myopathy can be alleviated with coQ10 supplementation. Nevertheless, due to a favourable safety profile, coQ10 can be tested in patients whose muscular symptoms cannot be managed otherwise....

Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage.

Science.gov (United States)

Lulli, Matteo; Witort, Ewa; Papucci, Laura; Torre, Eugenio; Schipani, Christian; Bergamini, Christian; Dal Monte, Massimo; Capaccioli, Sergio

2012-12-17

To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage. Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss. CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis. The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

Efficiency of emulsifier-free emulsions and emulsions containing rapeseed lecithin as delivery systems for vectorization and release of coenzyme Q10: physico-chemical properties and in vitro evaluation.

Science.gov (United States)

Kaci, M; Arab-Tehrany, E; Dostert, G; Desjardins, I; Velot, E; Desobry, S

2016-11-01

To improve the encapsulation and release of coenzyme Q10 (CoQ10), emulsifier-free-emulsions were developed with a new emulsification process using high-frequency ultrasound (HFU) at 1.7MHz. Nano-emulsions containing CoQ10 were prepared with or without rapeseed lecithin as an emulsifier. The emulsions prepared with HFU were compared with an emulsion of CoQ10 containing emulsifier prepared with the same emulsification technique as well as with emulsions prepared with low-frequency ultrasound coupled with high-pressure homogenization (LFU+HPH). The physico-chemical properties of the emulsions were determined by average droplet size measurement with nano-droplet tracking analysis, droplet surface charge with ζ potential measurement, surface tension and rheological behaviour. Emulsions made by LFU+HPH with an emulsifier showed lower droplet sizes due to cavitation generated by the HFU process. Surface tension results showed that there was no significant difference between emulsions containing lecithin emulsifier regardless of the preparation process or the inclusion of CoQ10. In vitro biocompatibility tests were performed on human mesenchymal stem cells in order to show the cytotoxicity of various formulations and the efficiency of CoQ10-loaded emulsions. In vitro tests proved that the vectors were not toxic. Furthermore, CoQ10 facilitated a high rate of cell proliferation and metabolic activity especially when in an emulsifier-free formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

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Courtney M. Anderson

2015-02-01

Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

A Direct Comparison of Anti-ulcer Effects of Coenzyme Q10 and Vitamin C on Indomethacin-induced Gastric Ulcer in Rat: A Controlled Experimental Study

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2013-08-01

Full Text Available Introduction: Indomethacin increases generation of mitochondrial reactive oxygen species (ROS which have a crucial role in the indomethacin-induced gastric ulcer. Coenzyme Q10 has an antioxidant activity on mitochondria and cell membranes and protects lipids from oxidation and is essential for stabilizing biological membranes. Superoxide dismutase (SOD acts as one of the defense mechanisms against free radicals. When the generation of ROS overwhelms, the antioxidant defense, lipid peroxiation of cell membrane occurs and cause cell damage. Materials and Methods: Male adult Wistar rats were divided into A and B groups. The rats in group A were then further divided into three subgroups of 6 animals each and received one of the following treatments: Animals in the first subgroup received saline. Animals in the second subgroup received saline and indomethacin. Animals in the third subgroup received vitamin C and indomethacin. The rats in group B were also further divided into 3 subgroups of 6 rats each and treated with one of the following treatments: Animals in first subgroup received 1% Tween 80 as vehicle. Animals In second subgroup received 1% Tween 80 and indomethacin. Animals in third subgroup received CoQ10 and indomethacin. Four hours after the last treatment, animals were killed and the stomachs removed were cut and gastric mucosal lesions were examined. Ulcer indexes were determined and SOD activity measured in plasma                                                             Results: Pretreatment with both vitamin C and coenzyme Q10 was associated with attenuation of ulcer index and increased SOD activity compared with animals treated with indomethacin alone (P

Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection

Czech Academy of Sciences Publication Activity Database

Alleva, R.; Tomasetti, M.; Anděra, Ladislav; Gellert, N.; Borghi, B.; Weber, C.; Murphy, M. P.; Neužil, J.

2001-01-01

Roč. 503, č. 1 (2001), s. 46-50 ISSN 0014-5793 R&D Projects: GA ČR GA301/99/0350 Institutional research plan: CEZ:AV0Z5052915 Keywords : coenzyme Q * apoptosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.644, year: 2001

Obesity-induced oocyte mitochondrial defects are partially prevented and rescued by supplementation with co-enzyme Q10 in a mouse model

Science.gov (United States)

Boots, C.E.; Boudoures, A.; Zhang, W.; Drury, A.; Moley, K.H.

2016-01-01

STUDY QUESTION Does supplementation with co-enzyme Q10 (CoQ10) improve the oocyte mitochondrial abnormalities associated with obesity in mice? SUMMARY ANSWER In an obese mouse model, CoQ10 improves the mitochondrial function of oocytes. WHAT IS KNOWN ALREADY Obesity impairs oocyte quality. Oocytes from mice fed a high-fat/high-sugar (HF/HS) diet have abnormalities in mitochondrial distribution and function and in meiotic progression. STUDY DESIGN, SIZE, DURATION Mice were randomly assigned to a normal, chow diet or an isocaloric HF/HS diet for 12 weeks. After 6 weeks on the diet, half of the mice receiving a normal diet and half of the mice receiving a HF/HS diet were randomly assigned to receive CoQ10 supplementation injections for the remaining 6 weeks. PARTICIPANTS/MATERIALS, SETTING, METHODS Dietary intervention was initiated on C57Bl6 female mice at 4 weeks of age, CoQ10 versus vehicle injections were assigned at 10 weeks, and assays were conducted at 16 weeks of age. Mice were super-ovulated, and oocytes were collected and stained to assess mitochondrial distribution, quantify reactive oxygen species (ROS), assess meiotic spindle formation, and measure metabolites. In vitro fertilization was performed, and blastocyst embryos were transferred into control mice. Oocyte number, fertilization rate, blastulation rate and implantation rate were compared between the four cohorts. Bivariate statistics were performed appropriately. MAIN RESULTS AND THE ROLE OF CHANCE HF/HS mice weighed significantly more than normal diet mice (29 versus 22 g, P< 0.001). CoQ10 supplementation did not influence weight. Levels of ATP, citrate, and phosphocreatine were lower and ROS levels were higher in HF/HS mice than in controls (P< 0.001). CoQ10 supplementation significantly increased the levels of metabolites and decreased ROS levels in oocytes from normal diet mice but not in oocytes from HF/HS mice. However, CoQ10 completely prevented the mitochondrial distribution abnormalities

Novel recessive mutations in COQ4 cause severe infantile cardiomyopathy and encephalopathy associated with CoQ10 deficiency

OpenAIRE

Sondheimer, Neal; Hewson, Stacy; Cameron, Jessie M.; Somers, Gino R.; Broadbent, Jane Dunning; Ziosi, Marcello; Quinzii, Catarina Maria; Naini, Ali B.

2017-01-01

Coenzyme Q10 (CoQ10) or ubiquinone is one of the two electron carriers in the mitochondrial respiratory chain which has an essential role in the process of oxidative phosphorylation. Defects in CoQ10 synthesis are usually associated with the impaired function of CoQ10–dependent complexes I, II and III. The recessively transmitted CoQ10 deficiency has been associated with a number of phenotypically and genetically heterogeneous groups of disorders manifesting at variable age of onset. The infa...

Coenzyme Q Metabolism Is Disturbed in High Fat Diet-Induced Non Alcoholic Fatty Liver Disease in Rats

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Kathleen M Botham

2012-02-01

Full Text Available Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD, the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control or a high fat diet (57% metabolizable energy as fat for 18 weeks. The concentrations of total (reduced + oxidized CoQ9 were increased by > 2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.

Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial single-photon emission tomography

Energy Technology Data Exchange (ETDEWEB)

Kim, Yong-ih [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Sawada, Yoshihiro [Department of Internal Medicine, Nishiyodo Hospital, Nishiyodo (Japan); Fujiwara, Go [Department of Radiology, Nishiyodo Hospital, Nishiyodo (Japan); Chiba, Hiroshi [Department of Internal Medicine, Mimihara General Hospital, Mimihara (Japan); Nishimura, Tsunehiko [Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Osaka (Japan)

1997-06-10

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64{+-}12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7{+-}12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slices x nine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39{+-}0.39 to 2.54{+-}0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1{+-}4.3, compared to 13.9{+-}4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2{+-}8.1 vs 19.7{+-}7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging. (orig.). With 5 figs., 1 tab.

CoQ10 and L-carnitine for statin myalgia?

Science.gov (United States)

DiNicolantonio, James J

2012-10-01

Statins are a standard of care in many clinical settings such as acute myocardial infarction and for patients having or at risk of cardiovascular (CV) disease. This is based on a plethora of data showing reductions in CV events and mortality. The CV benefit of statins can be partly explained by their ability to inhibit of HMG-CoA reductase, which subsequently lowers cholesterol and decreases the formation of mevalonate. However, the inhibition of the mevalonate pathway decreases the formation of coenzyme Q10 (CoQ10) within the body. It has been a long-standing theory that statin-associated muscle pain (myalgia) is caused, or at least partly contributed by, a reduction in CoQ10 levels in muscle mitochondria. One of the main side effects of statins is myalgia, which causes the patient to either stop their statin or significantly reduce the dose of their statin. The question of whether CoQ10 can help treat statin myopathy is a common one encountered by clinicians in current day practice.

Water-soluble coenzyme Q10 formulation (Q-TER(®)) in the treatment of presbycusis.

Science.gov (United States)

Salami, Angelo; Mora, Renzo; Dellepiane, Massimo; Manini, Giorgio; Santomauro, Valentina; Barettini, Luciano; Guastini, Luca

2010-10-01

These preliminary data are encouraging for a larger clinical trial to collect additional evidence on the effect of Q-TER(®) in preventing the development of hearing loss in subjects with presbycusis. The purpose of this study was to evaluate the efficiency and applicability of a water-soluble formulation of CoQ10 (Q-TER(®)) in subjects with presbycusis. A total of 60 patients with presbycusis were included and divided into three numerically equal groups. Group A underwent therapy with Q-TER(®), 160 mg, once a day for 30 days; group B underwent therapy with vitamin E (50 mg), once a day for 30 days; group C received placebo, once a day for 30 days. Before and at the end of the treatment, all patients underwent pure tone audiometry, transient evoked otoacoustic emissions, otoacoustic products of distortion, auditory brainstem response, and speech audiometry. Compared with group B, at the end of the treatment in group A the liminar tonal audiometry showed a significant improvement of the air and bone thresholds at the 1000 (14/20 vs 9/20), 2000 (14/20 vs 7/20), 4000 (15/20 vs 6/20), and 8000 Hz (13/20 vs 5/20). We found no significant differences in the other parameters and in group C.

Amelioration of Behavioural, Biochemical, and Neurophysiological Deficits by Combination of Monosodium Glutamate with Resveratrol/Alpha-Lipoic Acid/Coenzyme Q10 in Rat Model of Cisplatin-Induced Peripheral Neuropathy

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Naini Bhadri

2013-01-01

Full Text Available Cisplatin or cis-diamminedichloroplatinum (II (CDDP is a cytotoxic chemotherapeutic agent with dose-dependent peripheral neuropathy as a foremost side effect characterised by ataxia, pain, and sensory impairment. Cumulative drug therapy of CDDP is known to produce severe oxidative damage. It mainly targets and accumulates in dorsal root ganglia that in turn cause damage resulting in secondary nerve fibre axonopathy. In the present study, we investigated the neuroprotective effect of the combination of monosodium glutamate (MSG with three individual antioxidants, that is, resveratrol, alpha-lipoic acid (ALA, and coenzyme Q10 (CoQ10, in cisplatin (2 mg/kg i.p. twice weekly induced peripheral neuropathy in rats. After 8 weeks of treatment the degree of neuroprotection was determined by measuring behavioral and electrophysiological properties and sciatic nerve lipid peroxidation, as well as glutathione and catalase levels. The results suggested that pretreatment with the combination of MSG (500 mg/kg/day po with resveratrol (10 mg/kg/day i.p. or ALA (20 mg/kg/day i.p. or CoQ10 (10 mg/kg weekly thrice i.p. exhibited neuroprotective effect. The maximum neuroprotection of MSG was observed in the combination with resveratrol.

Identification and characterization of an archaeal ketopantoate reductase and its involvement in regulation of coenzyme A biosynthesis.

Science.gov (United States)

Tomita, Hiroya; Imanaka, Tadayuki; Atomi, Haruyuki

2013-10-01

Coenzyme A (CoA) biosynthesis in bacteria and eukaryotes is regulated primarily by feedback inhibition towards pantothenate kinase (PanK). As most archaea utilize a modified route for CoA biosynthesis and do not harbour PanK, the mechanisms governing regulation of CoA biosynthesis are unknown. Here we performed genetic and biochemical studies on the ketopantoate reductase (KPR) from the hyperthermophilic archaeon Thermococcus kodakarensis. KPR catalyses the second step in CoA biosynthesis, the reduction of 2-oxopantoate to pantoate. Gene disruption of TK1968, whose product was 20-29% identical to previously characterized KPRs from bacteria/eukaryotes, resulted in a strain with growth defects that were complemented by addition of pantoate. The TK1968 protein (Tk-KPR) displayed reductase activity specific for 2-oxopantoate and preferred NADH as the electron donor, distinct to the bacterial/eukaryotic NADPH-dependent enzymes. Tk-KPR activity decreased dramatically in the presence of CoA and KPR activity in cell-free extracts was also inhibited by CoA. Kinetic studies indicated that CoA inhibits KPR by competing with NADH. Inhibition of ketopantoate hydroxymethyltransferase, the first enzyme of the pathway, by CoA was not observed. Our results suggest that CoA biosynthesis in T. kodakarensis is regulated by feedback inhibition of KPR, providing a feasible regulation mechanism of CoA biosynthesis in archaea. © 2013 John Wiley & Sons Ltd.

Novel formulation and evaluation of a Q10-loaded solid lipid nanoparticle cream: in vitro and in vivo studies

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Farboud ES

2011-03-01

Full Text Available Effat Sadat Farboud, Saman Ahmad Nasrollahi, Zahra TabbakhiDepartment of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, IranAbstract: Solid lipid nanoparticles (SLNs of coenzyme Q10 (CoQ10 were formulated by a high-pressure homogenization method. The best formulation of SLN dispersion consisted of 13% lipid (cetyl palmitate or stearic acid, 8% surfactant (Tween 80 or Tego Care 450, and water. Stability tests, particle size analysis, differential scanning calorimetry, transmission electron microscopy, and release study were conducted to find the best formulation. A simple cream of CoQ10 and a cream containing CoQ10-loaded SLNs were prepared and compared on volunteers aged 20–30 years. SLNs with particle size between 50 nm and100 nm exhibited the most suitable stability. In vitro release profiles of CoQ10 from simple cream, SLN alone, and CoQ10-loaded SLN cream showed prolonged release for SLNs compared with the simple cream, whereas there was no significant difference between SLN alone and SLN in cream. In vitro release studies also demonstrated that CoQ10-loaded SLN and SLN cream possessed a biphasic release pattern in comparison with simple cream. In vivo skin hydration and elasticity studies on 25 volunteers suggested good dermal penetration and useful activity of Q10 on skin as a hydratant and antiwrinkle cream.Keywords: coenzyme Q10, SLN, release study 

Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate

Science.gov (United States)

Samoudi, Mojtaba; Omid Yeganeh, Negar; Shahbani Zahiri, Hossein; Shariati, Parvin; Hajhosseini, Reza

2015-01-01

Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli). Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transformed by the encoding gene for FPPS (ispA) under the control of either the trc or P BAD promoters. Results: Over-expression of ispA under the control of P BAD promoter led to a relative increase in CoQ 10 production only in recombinant E. coli Br although induction by arabinose resulted in partial reduction of CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains. Over-expression of ispA under the control of stronger trc promoter, however, led to a severe decrease in CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains, as reflected by reductions from 629±40 to 30±13 and 564±28 to 80±14 μg/g Dried Cell Weight (DCW), respectively. The results showed high level of FPP reduces endogenous CoQ 8 production as well and that CoQs are produced in a complimentary manner, as the increase in production of one decreases the production of the other. Conclusion: The reduction in CoQ 10 production can be a result of Dds inhibition by high FPP concentration. Therefore, more effort is needed to verify the role of intermediate metabolite concentration and to optimize production of CoQ 10 . PMID:26306151

Cerebellar Ataxia and Coenzyme Q Deficiency through Loss of Unorthodox Kinase Activity.

Science.gov (United States)

Stefely, Jonathan A; Licitra, Floriana; Laredj, Leila; Reidenbach, Andrew G; Kemmerer, Zachary A; Grangeray, Anais; Jaeg-Ehret, Tiphaine; Minogue, Catherine E; Ulbrich, Arne; Hutchins, Paul D; Wilkerson, Emily M; Ruan, Zheng; Aydin, Deniz; Hebert, Alexander S; Guo, Xiao; Freiberger, Elyse C; Reutenauer, Laurence; Jochem, Adam; Chergova, Maya; Johnson, Isabel E; Lohman, Danielle C; Rush, Matthew J P; Kwiecien, Nicholas W; Singh, Pankaj K; Schlagowski, Anna I; Floyd, Brendan J; Forsman, Ulrika; Sindelar, Pavel J; Westphall, Michael S; Pierrel, Fabien; Zoll, Joffrey; Dal Peraro, Matteo; Kannan, Natarajan; Bingman, Craig A; Coon, Joshua J; Isope, Philippe; Puccio, Hélène; Pagliarini, David J

2016-08-18

The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions. Although COQ8 was predicted to be a protein kinase, we demonstrate that it lacks canonical protein kinase activity in trans. Instead, COQ8 has ATPase activity and interacts with lipid CoQ intermediates, functions that are likely conserved across all domains of life. Collectively, our results lend insight into the molecular activities of the ancient UbiB family and elucidate the biochemical underpinnings of a human disease. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of n-3 fatty acids and coenzyme Q10 supplementation on neutrophil leukotrienes, mediators of inflammation resolution and myeloperoxidase in chronic kidney disease.

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Barden, Anne E; Shinde, Sujata; Burke, Valerie; Puddey, Ian B; Beilin, Lawrence J; Irish, Ashley B; Watts, Gerald F; Mori, Trevor A

2018-03-22

Neutrophils release leukotriene (LT)B 4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB 5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB 4 . This study evaluated the independent and combined effects of n-3 FA and CoQ supplementation on neutrophil leukotrienes, the pro-inflammatory eicosanoid 5-hydroxyeicosatetraenoic acid (5-HETE), SPM, and plasma MPO, in patients with CKD. In a double-blind, placebo-controlled intervention of factorial design, 85 patients with CKD were randomized to either n-3 FA (4 g), CoQ (200 mg), both supplements, or control (4 g olive oil), daily for 8 weeks. Plasma MPO and calcium ionophore-stimulated neutrophil release of LTs, 5-HETE and SPM were measured at baseline and after 8 weeks. Seventy four patients completed the intervention. n-3 FA, but not CoQ, significantly increased neutrophil LTB 5 (P n-3 FA or CoQ. Plasma MPO was significantly reduced with n-3 FA alone (P = 0.013) but not when given in combination with CoQ. n-3 FA supplementation in patients with CKD leads to increased neutrophil release of LTB 5 and several SPM, as well as a reduction in plasma MPO that may have important implications for limiting chronic inflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

Potential Cardiovascular and Renal Protective Effects of Vitamin D and Coenzyme Q10 in l-NAME-Induced Hypertensive Rats.

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Shamardl, Hanan A; El-Ashmony, Sahar M; Kamel, Hala F; Fatani, Sameer H

2017-08-01

Hypertension is one of the primary modifiable risk factors for cardiovascular disease. Adequate vitamin D (vit D) levels have been shown to reduce vascular smooth muscle contraction and to increase arterial compliance, which may be beneficial in hypertension. Further, coenzyme Q10 (COQ10) through its action to lower oxidative stress has been reported to have beneficial effects on hypertension and heart failure. This study examined the possible cardiac and renal protective effects of vit D and COQ10 both separately and in combination with an angiotensin II receptor blocker, valsartan (vals) in l-NAME hypertensive rats. Hypertension was induced in rats by l-NAME administration. Following induction of hypertension, the rats were assigned into the following 6 subgroups: an l-NAME alone group and treated groups receiving the following drugs intraperitoneally for 6 weeks; vals, vit D, COQ10 and combination of vals with either vit D or COQ10. A group of normotensive rats were used as negative controls. At the end of the treatment period, blood pressure, serum creatinine, blood urea nitrogen, lipids and serum, cardiac and renal parameters of oxidative stress were measured. Compared to the l-NAME only group, all treatments lowered systolic, diastolic, mean arterial pressure, total cholesterol, low-density lipoprotein cholesterol, and creatinine levels as well as TNF-α and malondialdehyde. Further, the agents increased serum, cardiac and renal total antioxidant capacity. Interestingly, the combination of agents had further effects on all the parameters compared to treatment with each single agent. The study suggests that the additive protective effects of vit D and COQ10 when used alone or concurrent with vals treatment in hypertensive rats may be due to their effects as antioxidants, anticytokines and blood pressure conservers. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Generation, genome edition and characterization of iPSC lines from a patient with coenzyme Q10 deficiency harboring a heterozygous mutation in COQ4 gene

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Damià Romero-Moya

2017-10-01

Full Text Available We report the generation, CRISPR/Cas9-edition and characterization of induced pluripotent stem cell (iPSC lines from a patient with coenzyme Q10 deficiency harboring the heterozygous mutation c.483G > C in the COQ4 gene. iPSCs were generated using non-integrative Sendai Viruses containing the reprogramming factors OCT4, SOX2, KLF4 and C-MYC. The iPSC lines carried the c.483G > C COQ4 mutation, silenced the OKSM expression and were mycoplasma-free. They were bona fide pluripotent cells as characterized by morphology, immunophenotype/gene expression for pluripotent-associated markers/genes, NANOG and OCT4 promoter demethylation, karyotype and teratoma formation. The COQ4 mutation was CRISPR/Cas9 edited resulting in isogenic, diploid and off-target free COQ4-corrected iPSCs.

Protective effect of coenzyme Q10 in simvastatin and gemfibrozil induced rhabdomyolysis in rats.

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Farswan, Mamta; Rathod, S P; Upaganlawar, A B; Semwal, Arvind

2005-10-01

Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis.

Coenzyme Q10 Protects Hippocampal Neurons Against Ischemia/Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

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M Zamani

2012-12-01

Full Text Available Introduction : Preliminary studies confirmed reduction in cell death following treatment with antioxidants. According to this finding we study the relationship between consumption of CoQ10 and expression of bax and bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis.Material & methods : We studied the protective role of CoQ10 against Ischemia-Reperfusion. Experimental design includes four groups: intact, ischemic control, sham control and treatment groups with CoQ10. The mice treated with CoQ10 as Pre - Treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction in inflammation (a week the mice post-treated with CoQ10.Nissl staining applied to counting necrotic cells of hippocampus and the western blotting performed to measurement the bax and bcl2 expression.Results :. Cell death was significantly lower when mice treated with CoQ10. Bax expression was significantly high in ischemic group but in treatment group was less and reversely the bcl2 expression in ischemic group was lower than treatment and vehicle groups.Conclusion : Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake significantly reduced cell death and prevented the expression of bax while inducing an increase in expression of bcl2.

Coenzyme Q10 Protects Hippocampal Neurons against Ischemia/ Reperfusion Injury via Modulation of BAX/Bcl-2 Expression

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Mohammad Zamani

2012-09-01

Full Text Available Introduction: Preliminary studies have con.rmed reduction in cell death following treatment with antioxidants. According to this .nding we study the relationship between consumption of CoQ10 and expression of Bax and Bcl2 in hippocampus following ischemia/reperfusion as proteins involved in cell programmed death or apoptosis. Methods: We studied the protective role of CoQ10 against ischemia-reperfusion. Experimental design includes four groups:  intact, ischemic control, sham control and treatment group with CoQ10. The mice were pre-treated with CoQ10 for a week, then ischemia was induced by common carotid artery ligation and following the reduction in in.ammation (a week the mice was treated with CoQ10.  Nissl staining was applied for counting the necrotic cells of hippocampus and the western blot was performed to measure the Bax and Bcl2 expression.Results: Cell death was signi.cantly lower when mice were treated with CoQ10. Bax expression was signi.cantly high in the ischemic group but low in the treatment group, and the bcl2 expression was lower in the ischemic group than the treatment and the vehicle groups.Discussion: Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake signi.cantly reduced cell death and prevented the expression of Bax while inducing an increase in expression of bcl2.

High serum coenzyme Q10, positively correlated with age, selenium and cholesterol in Inuit of Greenland

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Pedersen, Henning Sloth; Mortensen, S.A.; Rhode, M.

1999-01-01

impact. From a health survey we chose the subpopulation from the most remote area, where the traditional Greenlandic diet with high intake of sea mammals and fish predominates. The mean (SD) of S-CoQ10 in males was 1.495 (0.529) nmol/ml and 1.421 (0.629) nmol/ml in females, significantly higher (p ....001) compared to a Danish population. In a linear multiple regression model the S-CoQ10 level is significantly positively associated with age and S-selenium in males, and S-total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place...

Comprehensive behavioral testing in the R6/2 mouse model of Huntington's disease shows no benefit from CoQ10 or minocycline.

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Liliana B Menalled

2010-03-01

Full Text Available Previous studies of the effects of coenzyme Q10 and minocycline on mouse models of Huntington's disease have produced conflicting results regarding their efficacy in behavioral tests. Using our recently published best practices for husbandry and testing for mouse models of Huntington's disease, we report that neither coenzyme Q10 nor minocycline had significant beneficial effects on measures of motor function, general health (open field, rotarod, grip strength, rearing-climbing, body weight and survival in the R6/2 mouse model. The higher doses of minocycline, on the contrary, reduced survival. We were thus unable to confirm the previously reported benefits for these two drugs, and we discuss potential reasons for these discrepancies, such as the effects of husbandry and nutrition.

Autotrophic acetyl coenzyme A biosynthesis in Methanococcus maripaludis

International Nuclear Information System (INIS)

Shieh, J.; Whitman, W.B.

1988-01-01

To detect autotrophic CO 2 assimilation in cell extracts of Methanococcus maripaludis, lactate dehydrogenase and NADH were added to convert pyruvate formed from autotropically synthesized acetyl coenzyme A to lactate. The lactate produced was determined spectrophotometrically. When CO 2 fixation was pulled in the direction of lactate synthesis, CO 2 reduction to methane was inhibited. Bromoethanesulfonate (BES), a potent inhibitor of methanogenesis, enhanced lactate synthesis, and methyl coenzyme M inhibited it in the absence of BES. Lactate synthesis was dependent on CO 2 and H 2 , but H 2 + CO 2 -independent synthesis was also observed. In cell extracts, the rate of lactate synthesis was about 1.2 nmol min -1 mg of protein -1 . When BES was added, the rate of lactate synthesis increased to 2.1 nmol min -1 mg of protein -1 . Because acetyl coenzyme A did not stimulate lactate synthesis, pyruvate synthase may have been the limiting activity in these assays. Radiolabel from 14 CO 2 was incorporated into lactate. The percentages of radiolabel in the C-1, C-2, and C-3 positions of lactate were 73, 33, and 11%, respectively. Both carbon monoxide and formaldehyde stimulated lactate synthesis. 14 CH 2 O was specifically incorporated into the C-3 of lactate, and 14 CO was incorporated into the C-1 and C-2 positions. Low concentrations of cyanide also inhibited autotrophic growth, CO dehydrogenase activity, and autotrophic lactate synthesis. These observations are in agreement with the acetogenic pathway of autotrophic CO 2 assimilation

Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

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González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

2015-01-01

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

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Adrián González-Alonso

2015-09-01

Full Text Available An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

Coenzyme O*U1*UO, Alpha-Tocopherol and Free Cholesterol in HDL and LDL Fractions

DEFF Research Database (Denmark)

Johansen, Kurt; Theorell, Henning; Karlsson, Jan

1991-01-01

Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL......Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL...

The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure

DEFF Research Database (Denmark)

Mortensen, Svend A; Rosenfeldt, Franklin; Kumar, Adarsh

2014-01-01

.32 to 0.80; p = 0.003) by intention-to-treat analysis. The following secondary endpoints were significantly lower in the CoQ10 group compared with the placebo group: cardiovascular mortality (9% vs. 16%, p = 0.026), all-cause mortality (10% vs. 18%, p = 0.018), and incidence of hospital stays for HF (p...

Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism.

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Al-Ghamdi, Mashael; Al-Ayadhi, Laila; El-Ansary, Afaf

2014-02-25

Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA-treated rats demonstrated in a remarkable amelioration of most of the measured parameters. In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in

Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial

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Lindahl, Tomas L.; Svensson, Erland

2015-01-01

Background/Objectives Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q10, important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. Subjects/Methods 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. Results The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6 mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. Conclusion CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q10 combined. A reduced cardiovascular mortality could

Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial.

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Urban Alehagen

Full Text Available Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q10, important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality.437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots.The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6 mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group.CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q10 combined. A reduced cardiovascular mortality could be demonstrated in the active group

Self-Nanoemulsifying Drug Delivery System of Coenzyme (Q10) with Improved Dissolution, Bioavailability, and Protective Efficiency on Liver Fibrosis.

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Khattab, Abeer; Hassanin, Lobna; Zaki, Nashwah

2017-07-01

The aim of our investigation is to develop and characterize self-nanoemulsifying drug delivery systems (SNEDDS) of CoQ 10 to improve its water solubility, dissolution rate, and bioavailability, and then evaluate its biochemical and physiological effect on liver cirrhosis in rats compared with CoQ 10 powder. SNEDDS are isotropic and thermodynamically stable mixture of oil, surfactant, co-surfactant, and drug that form an oil/water nanoemulsion when added to aqueous phases with soft agitation. Upon administration, self-nanoemulsifying system becomes in contact with gastrointestinal fluid and forms o/w nanoemulsion by the aid of gastrointestinal motility. When the nanoemulsion is formed in the gastrointestinal tract, it presents the drug in a solubilized form inside small nano-sized droplets that provide a large surface area for enhancing the drug release and absorption. Solubility of CoQ 10 in various oils, surfactants, and co-surfactants were studied to identify the components of SNEDDS; pseudo-ternary phase diagrams were plotted to identify the efficient self-emulsifying regions. CoQ 10 -loaded SNEDDS were prepared using isopropyl myristate as oil; Cremophor El, Labrasol, or Tween80 as surfactant; and Transcutol as co-surfactant. The amount of CoQ 10 in each vehicle was 3%. The formulations that passed thermostability evaluation test were assessed for particle size analysis, morphological characterization, refractive index, zeta potential, viscosity, electroconductivity, drug release profile, as well as ex vivo permeability. Pharmacokinetics and hepatoprotective efficiency of the optimized SNEDDS of CoQ 10 compared with CoQ 10 suspension were performed. Results showed that all optimized formulae have the ability to form a good and stable nanoemulsion when diluted with water; the mean droplet size of all formulae was in the nanometric range (11.7-13.5 nm) with optimum polydispersity index values (0.2-0.21). All formulae showed negative zeta potential (-11.3 to -17

Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

International Nuclear Information System (INIS)

Sun, Haiyan; Li, Ying; Feng, Shengqiu; Zou, Weihua; Guo, Kai; Fan, Chunfen; Si, Shengli

2013-01-01

Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid

Analysis of five rice 4-coumarate:coenzyme A ligase enzyme activity and stress response for potential roles in lignin and flavonoid biosynthesis in rice

Energy Technology Data Exchange (ETDEWEB)

Sun, Haiyan [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); School of Biology and Food Engineering, Changshu Institute of Technology, Changshu 215500 (China); Li, Ying; Feng, Shengqiu; Zou, Weihua [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Guo, Kai [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Fan, Chunfen [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Si, Shengli [National Key Laboratory of Crop Genetic Improvement, Huazhong Agricultural University, Wuhan 430070 (China); Biomass and Bioenergy Research Centre, Huazhong Agricultural University, Wuhan 430070 (China); College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); and others

2013-01-18

Highlights: ► 4CLs play important roles in both lignin and flavonoids biosynthesis. ► PA and FA are the two main substrates of 4CL (Os4CL1/3/4/5) for lignin biosynthesis. ► Os4CL2 is suggested for flavonoid formation in defense against UV radiation. -- Abstract: 4-Coumarate:coenzyme A ligase (4CL) catalyzes the conversion of hydroxycinnamates into corresponding CoA esters for biosynthesis of flavonoids and lignin. In this study, five members of the 4CL gene family from rice were cloned and analyzed. Recombinant 4CL data revealed that 4-coumaric acid and ferulic acid were the two main substrates of 4CL (Os4CL1/3/4/5) for monolignol biosynthesis in rice. Os4CL2 was specifically expressed in the anther and was strongly activated by UV irradiation, suggesting its potential involvement in flavonoid formation. Moreover, bioinformatics analysis showed that the existence of valine residue at the substrate-binding pocket may mainly affect rice 4CL activities toward sinapic acid.

CoQ10 Deficiency May Indicate Mitochondrial Dysfunction in Cr(VI Toxicity

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Xiali Zhong

2017-04-01

Full Text Available To investigate the toxic mechanism of hexavalent chromium Cr(VI and search for an antidote for Cr(VI-induced cytotoxicity, a study of mitochondrial dysfunction induced by Cr(VI and cell survival by recovering mitochondrial function was performed. In the present study, we found that the gene expression of electron transfer flavoprotein dehydrogenase (ETFDH was strongly downregulated by Cr(VI exposure. The levels of coenzyme 10 (CoQ10 and mitochondrial biogenesis presented by mitochondrial mass and mitochondrial DNA copy number were also significantly reduced after Cr(VI exposure. The subsequent, Cr(VI-induced mitochondrial damage and apoptosis were characterized by reactive oxygen species (ROS accumulation, caspase-3 and caspase-9 activation, decreased superoxide dismutase (SOD and ATP production, increased methane dicarboxylic aldehyde (MDA content, mitochondrial membrane depolarization and mitochondrial permeability transition pore (MPTP opening, increased Ca2+ levels, Cyt c release, decreased Bcl-2 expression, and significantly elevated Bax expression. The Cr(VI-induced deleterious changes were attenuated by pretreatment with CoQ10 in L-02 hepatocytes. These data suggest that Cr(VI induces CoQ10 deficiency in L-02 hepatocytes, indicating that this deficiency may be a biomarker of mitochondrial dysfunction in Cr(VI poisoning and that exogenous administration of CoQ10 may restore mitochondrial function and protect the liver from Cr(VI exposure.

Effect of cooking and in vitro digestion on the stability of co-enzyme Q10 in processed meat products.

Science.gov (United States)

Tobin, Brian D; O'Sullivan, Maurice G; Hamill, Ruth; Kerry, Joseph P

2014-05-01

The use of CoQ10 fortification in the production of a functional food has been demonstrated in the past but primarily for dairy products. This study aimed to determine the bio-accessibility of CoQ10 in processed meat products, beef patties and pork breakfast sausages, fortified with CoQ10. Both the patties and sausages were fortified with a micellarized form of CoQ10 to enhance solubility to a concentration of 1mg/g of sample (NovaSolQ®). An assay was developed combining in vitro digestion and HPLC analysis to quantify the CoQ10 present in fortified products (100mg/g). The cooking retention level of CoQ10 in the products was found to be 74±1.42% for patties and 79.69±0.75% for sausages. The digestibility for both products ranged between 93% and 95%, sausages did have a higher digestibility level than patties but this was not found to be significant (P<0.01). Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of coenzyme Q10 supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials.

Science.gov (United States)

Mazidi, Mohsen; Kengne, Andre Pascal; Banach, Maciej

2018-02-01

The aim of this systematic review and meta-analysis of prospective interventional studies was to investigate the effects of coenzyme Q10 (CQ10) on plasma C-reactive protein (CRP) levels. PubMed/Medline, Web of Science (WoS), Cochrane Database and Google Scholar databases were searched (up to December 2016) to identify prospective studies evaluating the impact of CQ10 supplementation on CRP. Random effects models meta-analysis was used for quantitative data synthesis. Sensitivity analysis used the leave-one-out method, and heterogeneity was quantitatively assessed using the I 2 index. Systematic review PROSPERO database registration: CRD42016038155. From a total of 119 entries identified via searches, 7 studies were finally included to the analysis. The results of the meta-analysis indicated a non-significant reduction in CRP concentrations following supplementation with CQ10 with a weighted mean difference [WMD] of -0.25mg/l (95% confidence intervals [CI] -0.56 to 0.06, I 2 =42.0%). The WMD for the effects on interleukin 6 (IL6) was -0.72pg/dl, (95% CI -1.24 to -0.24, I 2 =51.8%). These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in plasma CRP levels were independent of the dosage of CQ10 (slope: -0.0005; 95% CI: -0.005, 0.004; p=0.832) while duration of supplementation was the dependent mediator (slope: slope: -0.111; 95% CI: -0.21, -0.004; p=0.042). In conclusion, CQ10 supplementation has a borderline favourable effect on CRP levels, and a significant effect on IL-6 level. This suggests that CQ10 supplementation likely attenuates subclinical inflammation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10

Science.gov (United States)

Mao, Zhigang; Wu, Jeffrey H.; Dong, Tingting; Wu, Mei X.

2016-02-01

Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study.

Additive enhancement of wound healing in diabetic mice by low level light and topical CoQ10.

Science.gov (United States)

Mao, Zhigang; Wu, Jeffrey H; Dong, Tingting; Wu, Mei X

2016-02-02

Diabetes, a highly prevalent disease that affects 9.3% of Americans, often leads to severe complications and slow wound healing. Preclinical studies have suggested that low level light therapy (LLLT) can accelerate wound healing in diabetic subjects, but significant improvements must be made to overcome the absence of persuasive evidence for its clinical use. We demonstrate here that LLLT can be combined with topical Coenzyme Q10 (CoQ10) to heal wounds in diabetic mice significantly faster than LLLT alone, CoQ10 alone, or controls. LLLT followed by topical CoQ10 enhanced wound healing by 68~103% in diabetic mice in the first week and more than 24% in the second week compared with untreated controls. All wounds were fully healed in two weeks following the dual treatment, in contrast to only 50% wounds or a fewer being fully healed for single or sham treatment. The accelerated healing was corroborated by at least 50% higher hydroxyproline levels, and tripling cell proliferation rates in LLLT and CoQ10 treated wounds over controls. The beneficial effects on wound healing were probably attributed to additive enhancement of ATP production by LLLT and CoQ10 treatment. The combination of LLLT and topical CoQ10 is safe and convenient, and merits further clinical study.

Cerebellar Ataxia and Coenzyme Q Deficiency Through Loss of Unorthodox Kinase Activity

OpenAIRE

Stefely, Jonathan A.; Licitra, Floriana; Laredj, Leila; Reidenbach, Andrew G.; Kemmerer, Zachary A.; Grangeray, Anais; Jaeg-Ehret, Tiphaine; Minogue, Catherine E.; Ulbrich, Arne; Hutchins, Paul D.; Wilkerson, Emily M.; Ruan, Zheng; Aydin, Deniz; Hebert, Alexander S.; Guo, Xiao

2016-01-01

The UbiB protein kinase-like (PKL) family is widespread—comprising one-quarter of microbial PKLs and five human homologs—yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical ana...

The Combination of Physical Exercise with Muscle-Directed Antioxidants to Counteract Sarcopenia: A Biomedical Rationale for Pleiotropic Treatment with Creatine and Coenzyme Q10

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Michele Guescini

2017-01-01

Full Text Available Sarcopenia represents an increasing public health risk due to the rapid aging of the world’s population. It is characterized by both low muscle mass and function and is associated with mobility disorders, increased risk of falls and fractures, loss of independence, disabilities, and increased risk of death. Despite the urgency of the problem, the development of treatments for sarcopenia has lagged. Increased reactive oxygen species (ROS production and decreased antioxidant (AO defences seem to be important factors contributing to muscle impairment. Studies have been conducted to verify whether physical exercise and/or AOs could prevent and/or delay sarcopenia through a normalization of the etiologically relevant ROS imbalance. Despite the strong rationale, the results obtained were contradictory, particularly with regard to the effects of the tested AOs. A possible explanation might be that not all the agents included in the general heading of “AOs” could fulfill the requisites to counteract the complex series of events causing/accelerating sarcopenia: the combination of the muscle-directed antioxidants creatine and coenzyme Q10 with physical exercise as a biomedical rationale for pleiotropic prevention and/or treatment of sarcopenia is discussed.

The complete coenzyme B12 biosynthesis gene cluster of Lactobacillus reuteri CRL 1098

NARCIS (Netherlands)

Santos, dos F.; Vera, J.L.; Heijden, van der R.; Valdez, G.F.; Vos, de W.M.; Sesma, F.; Hugenholtz, J.

2008-01-01

The coenzyme B12 production pathway in Lactobacillus reuteri has been deduced using a combination of genetic, biochemical and bioinformatics approaches. The coenzyme B12 gene cluster of Lb. reuteri CRL1098 has the unique feature of clustering together the cbi, cob and hem genes. It consists of 29

The glossyhead1 allele of acc1 reveals a principal role for multidomain acetyl-coenzyme a carboxylase in the biosynthesis of cuticular waxes by Arabidopsis

KAUST Repository

Lu, Shiyou

2011-09-23

A novel mutant of Arabidopsis (Arabidopsis thaliana), having highly glossy inflorescence stems, postgenital fusion in floral organs, and reduced fertility, was isolated from an ethyl methanesulfonate-mutagenized population and designated glossyhead1 (gsd1). The gsd1 locus was mapped to chromosome 1, and the causal gene was identified as a new allele of Acetyl-Coenzyme A Carboxylase1 (ACC1), a gene encoding the main enzyme in cytosolic malonyl-coenzyme A synthesis. This, to our knowledge, is the first mutant allele of ACC1 that does not cause lethality at the seed or early germination stage, allowing for the first time a detailed analysis of ACC1 function in mature tissues. Broad lipid profiling of mature gsd1 organs revealed a primary role for ACC1 in the biosynthesis of the very-long-chain fatty acids (C 20:0 or longer) associated with cuticular waxes and triacylglycerols. Unexpectedly, transcriptome analysis revealed that gsd1 has limited impact on any lipid metabolic networks but instead has a large effect on environmental stress-responsive pathways, especially senescence and ethylene synthesis determinants, indicating a possible role for the cytosolic malonyl-coenzyme A-derived lipids in stress response signaling. © 2011 American Society of Plant Biologists. All Rights Reserved.

High serum coenzyme Q10, positively correlated with age, selenium and cholesterol, in Inuit of Greenland. A pilot study

DEFF Research Database (Denmark)

Pedersen, H S; Mortensen, S A; Rohde, M

1999-01-01

.001) compared to a Danish population. In a linear multiple regression model the S-CoQ10 level is significantly positively associated with age and S-selenium in males, and S-total cholesterol in females. The high level of CoQ10 in Greenlanders probably reflects diet, since no bioaccumulation takes place...

Coenzyme Q10 (PDQ)

Science.gov (United States)

... NIH). NIH is the federal government’s center of biomedical research. The PDQ summaries are based on an independent ... NCCIH) are sponsoring a number of clinical trials (research studies) at medical centers to test CAM therapies for use in cancer. Conventional approaches to cancer ...

Various endocrine disorders in children with t(13;14(q10;q10 Robertsonian translocation

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Byung Ho Choi

2013-09-01

Full Text Available Purpose45,XY,t(13;14(q10;q10 karyotype can suggest infertility associated with more or less severe oligospermia in male adults. In addition, 45,XX,t(13;14(q10;q10 karyotype carries reproductive risks such as miscarriage or infertility in female adults. However, reports on the phenotype of this karyotype in children are very rare. This study was done to observe various phenotypes of this karyotype in children.MethodsBetween January 2007 and December 2012, children diagnosed with 45,XY,t(13;14(q10;q10 or 45,XX,t(13;14(q10;q10 karyotype by chromosome analysis were analyzed retrospectively.ResultsEight children (5 boys and 3 girls were diagnosed with 45,XY,t(13;14(q10;q10 or 45,XX,t(13;14(q10;q10 karyotype. They ranged in age from 5 years and 6 months to 12 years and 4 months. The phenotypes of the study patients consisted of 1 hypogonadotrophic hypogonadism, 1 precocious puberty, 3 early puberty, 2 growth hormone deficiency (GHD (partial and 1 idiopathic short stature. As shown here t(13;14(q10;q10 Robertsonian translocation shows a wide range of phenotypes.ConclusionIt can be said that t(13;14(q10;q10 Robertsonian translocation shows various phenotypes from GHD to precocious puberty in children. Further large-scale studies are necessary.

Effect of Magnetic Field Exposure on Testicular function and Prophylactic Role of Coenzyme Q10 and L-Carnitine in Mice

International Nuclear Information System (INIS)

Ramadan, L.A.; Abd-Allah, A.R.A.; Aly, H.A.A.

2004-01-01

The protective effect of L-carnitine or Co enzyme Q 10 (Co Q 10) against high magnetic field (20 mt) induced testicular toxicity in mice was evaluated. Animals were injected with L-carnitine (200 mg/kg i.p.) or Co Q 10(200 mg/kg per o.s.) 1 hr before exposure to fractionated doses (1/2 h/day, 3 times per week for 2 weeks) or acute dose (3 hr) of magnetic field. Total sperm count motility, daily sperm production and testicular LDH-X activity as well as histopathological examination were investigated. Exposure of mice to fractionated doses of magnetic field caused a significant decrease in sperm count, motility, daily sperm production and LDH-X activity,which were more pronounced than those of acute dose. Moreover,marked testicular histopathological changes were observed after exposure to fractionated doses of magnetic field. Pretreatment of mice with L-carnitine or Co Q 10 1 hr before exposure to the magnetic field caused a significant recovery of testicular damage induced by high magnetic field (20 mT)

Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial

Science.gov (United States)

Alexander, Jan; Aaseth, Jan

2016-01-01

Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 μg Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 μg/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; 85 μg/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration

Validated HPLC method for the quantitative determination of CoQ(10) in dog plasma and its application to a pharmacokinetic study.

Science.gov (United States)

Yuan, Bo; Liu, Chunling; Xu, Pingwei; Lin, Lin; Pan, Cheng; Wang, Linglan; Xu, Haiyan

2011-09-01

Coenzyme Q(10) (CoQ(10) ) is a naturally occurring compound located in all membranes throughout the cell. A rapid and sensitive HPLC method was developed to determine the concentration of CoQ(10) in dog plasma using a surrogate matrix. Chromatographic separation was carried out on a Diamonsil C(18) column with the UV detector set at 275 nm. Methanol-2-propanol (40:60, v/v) was used as a mobile phase delivered at a flow rate of 1.0 mL/min. Calibrators were prepared using blank plasma-K(2) HPO(4) buffer (50 mm, pH 8.0)-saline (1:3:6, v/v/v) as surrogate matrix. It was shown that the surrogate matrix had similar properties to dog plasma for CoQ(10) in extraction, freeze-thaw and stability. The assay was linear over the concentration range of 0.10-100 µg/mL. The intra- and inter-day precisions were within 13.3% in terms of relative standard deviation (RSD%) and the accuracy was within ±7.5% in terms of relative error. This simple and reproducible HPLC method with less plasma volume (0.4 mL) and adequate sensitivity was successfully applied to pharmacokinetic studies of CoQ(10) in dogs and an investigation of the effect of CoQ(10) formulation on CoQ(10) baseline levels. Copyright © 2010 John Wiley & Sons, Ltd.

Effects of dietary coenzyme Q10 supplementation on hepatic mitochondrial function and the activities of respiratory chain-related enzymes in ascitic broiler chickens.

Science.gov (United States)

Geng, A L; Guo, Y M

2005-10-01

1. One hundred and sixty 1-d-old Arbor Acre male broiler chicks were fed with maize-soybean based diets for 6 weeks in a 2 x 2 factorial experiment. The factors were CoQ10 supplementation (0 or 40 mg/kg) and Escherichia coli lipopolysaccharide (LPS) challenge (LPS or saline). 2. CoQ10 was supplemented from d 1. From d 18, the chickens received three weekly i.p. injections of LPS (1.0 mg/kg BW) or an equivalent amount of sterile saline as control. From d 10 on, all chickens were exposed to low ambient temperature (12 to 15 degrees C) to induce ascites. 3. The blood packed cell volume and ascites heart index of broiler chickens were reduced by dietary CoQ10 supplementation. Mitochondrial State 3 and State 4 respiration, respiratory control ratio and phosphate oxygen ratio were not changed, but H+/site stoichiometry of complex II + III was elevated by dietary CoQ10 supplementation. 4. Cytochrome c oxidase and H+-ATPase activity were increased by CoQ10 supplementation, whereas NADH cytochrome c reductase and succinate cytochrome c reductase were not influenced. Mitochondrial anti-ROS capability was increased and malondialdehyde content was decreased by CoQ10 supplementation. 5. The work suggested that dietary CoQ10 supplementation could reduce broiler chickens' susceptibility to ascites, which might be the result of improving hepatic mitochondrial function, some respiratory chain-related enzymes activities and mitochondrial antioxidative capability.

A possible prebiotic synthesis of pantetheine, a precursor to coenzyme A

Science.gov (United States)

Keefe, A. D.; Newton, G. L.; Miller, S. L.

1995-01-01

The involvement of coenzyme A in many enzyme reactions suggests that it acted in this capacity very early in the development of life on Earth. Particularly relevant in this regard is its role in the activation of amino acids and hydroxy acids in the biosynthesis of some peptide antibiotics--a mechanism of peptide synthesis that forms the basis for the proposal that a thioester world could have preceded the RNA world. The components of coenzyme A have been shown to be probable prebiotic compounds: beta-alanine, pantoyl lactone and cysteamine and possibly adenosine. We show here that the pantetheine moiety of coenzyme A (which also occurs in a number of enzymes) can be synthesized in yields of several per cent by heating pantoyl lactone, beta-alanine and cysteamine at temperatures as low as 40 degrees C. These components are extremely soluble and so would have been preferentially concentrated in evaporating bodies of water, for example on beaches and at lagoon margins. Our results show that amide bonds can be formed at temperatures as low as 40 degrees C, and provide circumstantial support for the suggestion that pantetheine and coenzyme A were important in the earliest metabolic systems.

Self-reported adherence and biomarker levels of CoQ10 and alpha-tocopherol

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Vitolins MZ

2018-04-01

Full Text Available Mara Z Vitolins,1 L Douglas Case,1 Stephen R Rapp,2 Mark O Lively,3 Edward G Shaw,4 Michelle J Naughton,5 Jeffrey Giguere,6 Glenn J Lesser7 1Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Internal Medicine-Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA; 5Department of Internal Medicine, The Ohio State University, Columbus, OH, USA; 6Greenville Community Oncology Research Program of the Carolinas, Greenville, SC, USA; 7Department of Internal Medicine-Hematology and Oncology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC, USA Purpose: Women with breast cancer were randomized to receive coenzyme Q10 (CoQ10 plus Vitamin E or placebo in a clinical trial. The objective of this evaluation is to examine the association between participant self-reported adherence to the study supplements and changes in plasma biomarker levels.Patients and methods: Correlation coefficients quantified the association between changes in alpha-tocopherol and CoQ10 levels and the association between self-reported adherence and changes in biomarkers. Participants were categorized by self-reported adherence; Kruskal–Wallis tests compared changes in alpha-tocopherol and CoQ10 levels between self-reported adherence groups.Results: Women (N=155 provided baseline and post-treatment biomarkers; 147 completed at least one diary. While changes in alpha-tocopherol and CoQ10 levels were moderately correlated, correlations ranged from 0.40 to 0.48, association between self-reported adherence and plasma alpha-tocopherol or CoQ10 levels was weak; correlations ranged from 0.10 to 0.29 at weeks 8, 16, and 24. Some participants with high self-reported adherence actually

Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration

International Nuclear Information System (INIS)

Zampol, Mariana A.; Busso, Cleverson; Gomes, Fernando; Ferreira-Junior, Jose Ribamar; Tzagoloff, Alexander; Barros, Mario H.

2010-01-01

Research highlights: → COQ10 deletion elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q 2 , a synthetic diffusible ubiquinone. → The significance that purified Coq10p contains bound Q 6 was examined by testing over-expression of Coq10p on respiration. → Inhibition of CoQ function due to Coq10p excess strength our hypothesis of Coq10p function in CoQ delivery. → Respiratory deficiency caused by more Coq10p was specific and restored by Q 2 in mitochondria or by Coq8p in cells. → Coq8p over-production on other coq mutants revealed a surprisingly higher stability of other Coq proteins. -- Abstract: COQ10 deletion in Saccharomyces cerevisiae elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q 2 . Rescue of respiration by Q 2 is a characteristic of mutants blocked in coenzyme Q 6 synthesis. Unlike Q 6 deficient mutants, mitochondria of the coq10 null mutant have wild-type concentrations of Q 6 . The physiological significance of earlier observations that purified Coq10p contains bound Q 6 was examined in the present study by testing the in vivo effect of over-expression of Coq10p on respiration. Mitochondria with elevated levels of Coq10p display reduced respiration in the bc1 span of the electron transport chain, which can be restored with exogenous Q 2 . This suggests that in vivo binding of Q 6 by excess Coq10p reduces the pool of this redox carrier available for its normal function in providing electrons to the bc1 complex. This is confirmed by observing that extra Coq8p relieves the inhibitory effect of excess Coq10p. Coq8p is a putative kinase, and a high-copy suppressor of the coq10 null mutant. As shown here, when over-produced in coq mutants, Coq8p counteracts turnover of Coq3p and Coq4p subunits of the Q-biosynthetic complex. This can account for the observed rescue by COQ8 of the respiratory defect in strains over-producing Coq10p.

Over-expression of COQ10 in Saccharomyces cerevisiae inhibits mitochondrial respiration

Energy Technology Data Exchange (ETDEWEB)

Zampol, Mariana A.; Busso, Cleverson; Gomes, Fernando [Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo (Brazil); Ferreira-Junior, Jose Ribamar [Escola de Artes, Ciencias e Humanidades, Universidade de Sao Paulo, Sao Paulo (Brazil); Tzagoloff, Alexander [Department of Biological Sciences, Columbia University, NY (United States); Barros, Mario H., E-mail: mariohb@usp.br [Departamento de Microbiologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo (Brazil)

2010-11-05

Research highlights: {yields} COQ10 deletion elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q{sub 2}, a synthetic diffusible ubiquinone. {yields} The significance that purified Coq10p contains bound Q{sub 6} was examined by testing over-expression of Coq10p on respiration. {yields} Inhibition of CoQ function due to Coq10p excess strength our hypothesis of Coq10p function in CoQ delivery. {yields} Respiratory deficiency caused by more Coq10p was specific and restored by Q{sub 2} in mitochondria or by Coq8p in cells. {yields} Coq8p over-production on other coq mutants revealed a surprisingly higher stability of other Coq proteins. -- Abstract: COQ10 deletion in Saccharomyces cerevisiae elicits a defect in mitochondrial respiration correctable by addition of coenzyme Q{sub 2}. Rescue of respiration by Q{sub 2} is a characteristic of mutants blocked in coenzyme Q{sub 6} synthesis. Unlike Q{sub 6} deficient mutants, mitochondria of the coq10 null mutant have wild-type concentrations of Q{sub 6}. The physiological significance of earlier observations that purified Coq10p contains bound Q{sub 6} was examined in the present study by testing the in vivo effect of over-expression of Coq10p on respiration. Mitochondria with elevated levels of Coq10p display reduced respiration in the bc1 span of the electron transport chain, which can be restored with exogenous Q{sub 2}. This suggests that in vivo binding of Q{sub 6} by excess Coq10p reduces the pool of this redox carrier available for its normal function in providing electrons to the bc1 complex. This is confirmed by observing that extra Coq8p relieves the inhibitory effect of excess Coq10p. Coq8p is a putative kinase, and a high-copy suppressor of the coq10 null mutant. As shown here, when over-produced in coq mutants, Coq8p counteracts turnover of Coq3p and Coq4p subunits of the Q-biosynthetic complex. This can account for the observed rescue by COQ8 of the respiratory defect in strains

Coenzyme Q10 effect in prevention of atrial fibrillation after Coronary Artery Bypass Graft: double-blind randomized clinical trial

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Jalal Moludi

2015-05-01

Results: Thirty-eight women and forty-two men with a mean age of 58.37±7.98 years were enrolled in the study in two CoQ10 and placebo groups (each consisting of 40 patients. The incidence of postoperative AF was 45% in the control group to 20% in the intervention group decreased after supplementation (P=0.030. ICU stay and length of in-hospital stay did not significant. The incidence of arrhythmias ventricular tachycardia (VT and VF in this period was not significant (P=0.865. Conclusion: Q10 supplements have low side effects. Due to the reduction in the incidence of AF in patients after, CABG, these supplements can be recommended for the prevention of AF.

UPLC/Q-TOF MS-based metabolomics and qRT-PCR in enzyme gene screening with key role in triterpenoid saponin biosynthesis of Polygala tenuifolia.

Science.gov (United States)

Zhang, Fusheng; Li, Xiaowei; Li, Zhenyu; Xu, Xiaoshuang; Peng, Bing; Qin, Xuemei; Du, Guanhua

2014-01-01

The dried root of Polygala tenuifolia, named Radix Polygalae, is a well-known traditional Chinese medicine. Triterpenoid saponins are some of the most important components of Radix Polygalae extracts and are widely studied because of their valuable pharmacological properties. However, the relationship between gene expression and triterpenoid saponin biosynthesis in P. tenuifolia is unclear. In this study, ultra-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (Q-TOF MS)-based metabolomic analysis was performed to identify and quantify the different chemical constituents of the roots, stems, leaves, and seeds of P. tenuifolia. A total of 22 marker compounds (VIP>1) were explored, and significant differences in all 7 triterpenoid saponins among the different tissues were found. We also observed an efficient reference gene GAPDH for different tissues in this plant and determined the expression level of some genes in the triterpenoid saponin biosynthetic pathway. Results showed that MVA pathway has more important functions in the triterpenoid saponin biosynthesis of P. tenuifolia. The expression levels of squalene synthase (SQS), squalene monooxygenase (SQE), and beta-amyrin synthase (β-AS) were highly correlated with the peak area intensity of triterpenoid saponins compared with data from UPLC/Q-TOF MS-based metabolomic analysis. This finding suggested that a combination of UPLC/Q-TOF MS-based metabolomics and gene expression analysis can effectively elucidate the mechanism of triterpenoid saponin biosynthesis and can provide useful information on gene discovery. These findings can serve as a reference for using the overexpression of genes encoding for SQS, SQE, and/or β-AS to increase the triterpenoid saponin production of P. tenuifolia.

UPLC/Q-TOF MS-based metabolomics and qRT-PCR in enzyme gene screening with key role in triterpenoid saponin biosynthesis of Polygala tenuifolia.

Directory of Open Access Journals (Sweden)

Fusheng Zhang

Full Text Available The dried root of Polygala tenuifolia, named Radix Polygalae, is a well-known traditional Chinese medicine. Triterpenoid saponins are some of the most important components of Radix Polygalae extracts and are widely studied because of their valuable pharmacological properties. However, the relationship between gene expression and triterpenoid saponin biosynthesis in P. tenuifolia is unclear.In this study, ultra-performance liquid chromatography (UPLC coupled with quadrupole time-of-flight mass spectrometry (Q-TOF MS-based metabolomic analysis was performed to identify and quantify the different chemical constituents of the roots, stems, leaves, and seeds of P. tenuifolia. A total of 22 marker compounds (VIP>1 were explored, and significant differences in all 7 triterpenoid saponins among the different tissues were found. We also observed an efficient reference gene GAPDH for different tissues in this plant and determined the expression level of some genes in the triterpenoid saponin biosynthetic pathway. Results showed that MVA pathway has more important functions in the triterpenoid saponin biosynthesis of P. tenuifolia. The expression levels of squalene synthase (SQS, squalene monooxygenase (SQE, and beta-amyrin synthase (β-AS were highly correlated with the peak area intensity of triterpenoid saponins compared with data from UPLC/Q-TOF MS-based metabolomic analysis.This finding suggested that a combination of UPLC/Q-TOF MS-based metabolomics and gene expression analysis can effectively elucidate the mechanism of triterpenoid saponin biosynthesis and can provide useful information on gene discovery. These findings can serve as a reference for using the overexpression of genes encoding for SQS, SQE, and/or β-AS to increase the triterpenoid saponin production of P. tenuifolia.

Novel solid self-emulsifying drug delivery system of coenzyme Q₁₀ with improved photochemical and pharmacokinetic behaviors.

Science.gov (United States)

Onoue, Satomi; Uchida, Atushi; Kuriyama, Kazuki; Nakamura, Tatsuya; Seto, Yoshiki; Kato, Masashi; Hatanaka, Junya; Tanaka, Toshiyuki; Miyoshi, Hiroyuki; Yamada, Shizuo

2012-08-15

The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q(10) (CoQ(10)/s-SEDDS) with high photostability and oral bioavailability. The CoQ(10)/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ(10), medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ(10)/s-SEDDS powder with a diameter of ca. 15 μm was obtained by spray-drying, in which the CoQ(10) was mostly amorphized. The CoQ(10)/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280 nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ(10) exposed to simulated sunlight (250W/m(2)), suggesting potent photoreactivity. Nano-emulsified solution of CoQ(10) under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ(10), although the CoQ(10)/s-SEDDS was less photoreactive. After the oral administration of CoQ(10)/s-SEDDS (100 mg-CoQ(10)/kg) in rats, enhanced exposure of CoQ(10) was observed with increases in both C(max) and AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ(10). From the improved physicochemical and pharmacokinetic data, the s-SEDDS approach upon spray-drying might be a suitable dosage option for enhancing nutraceutical and pharmaceutical values of CoQ(10). Copyright © 2012 Elsevier B.V. All rights reserved.

Determination of a method for extraction of coenzyme Q10 in human plasma: optimization of the use of surfactants and other variables

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Claudia Cristina Ferreiro-Barros

2012-06-01

Full Text Available Objective: To establish a routine for the extraction of the total levelsof CoQ10 in human plasma through the Ultra High Performance LiquidChromatography (UHPLC. Methods: Two extraction protocolswere tested: a methanol: hexane and b 1-propanol. The followingparameters were analyzed: extraction temperature (19ºC and 4ºC,extraction tubes (glass and polypropylene, and surfactants (SDS,Triton X-100, Tween-20 at different concentrations, i.e., 1%,3%, 5% and 10%. Results: The results showed that the methodof extraction of CoQ10 in a sample of human plasma at 4ºC, usingsolvents methanol: hexane (85:15, v/v in the presence of surfactantTween-20 at 3% and polypropylene tubes showed better efficiencyand reproducibility when compared to the method with 1-propanol.Conclusion: By the analyses performed, it was possible to observethat the addition of the surfactant Tween-20 promoted an increasein the recovery of CoQ10 by the methanol:hexane extraction method.This method showed good reproducibility, with a low coefficient ofvariation and high sensitivity, since CoQ10 was detected in samplesof plasma of a control individual using a UV-type detector. The useof UHPLC equipment allowed a total analysis with total run time of3.5 minutes, enabling the rapid achievement of results, consideredmandatory for laboratory routines.

Characterization of Benzoyl Coenzyme A Biosynthesis Genes in the Enterocin-Producing Bacterium “Streptomyces maritimus”

Science.gov (United States)

Xiang, Longkuan; Moore, Bradley S.

2003-01-01

The novel benzoyl coenzyme A (benzoyl-CoA) biosynthesis pathway in “Streptomyces maritimus” was investigated through a series of target-directed mutations. Genes involved in benzoyl-CoA formation were disrupted through single-crossover homologous recombination, and the resulting mutants were analyzed for their ability to biosynthesize the benzoyl-CoA-primed polyketide antibiotic enterocin. Inactivation of the unique phenylalanine ammonia-lyase-encoding gene encP was previously shown to be absolutely required for benzoyl-CoA formation in “S. maritimus”. The fatty acid β-oxidation-related genes encH, -I, and -J, on the other hand, are necessary but not required. In each case, the yield of benzoyl-CoA-primed enterocin dropped below wild-type levels. We attribute the reduced benzoyl-CoA formation in these specific mutants to functional substitution and cross-talk between the products of genes encH, -I, and -J and the enzyme homologues of primary metabolism. Disruption of the benzoate-CoA ligase encN gene did not perturb enterocin production, however, demonstrating that encN is extraneous and that benzoic acid is not a pathway intermediate. EncN rather serves as a substitute pathway for utilizing exogenous benzoic acid. These experiments provide further support that benzoyl-CoA is formed in a novel bacterial pathway that resembles the eukaryotic assembly of benzoyl-CoA from phenylalanine via a β-oxidative path. PMID:12511484

A first case of primary amenorrhea with i(X(qter---q10::---qter, rob(13;14(q10;q10, inv(9(p13q33 karyotype

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Seema Korgaonkar

2011-01-01

Full Text Available Primary amenorrhea (PA refers to the absence of menarche by the age of 16-18 years although secondary sexual characters are developed. PA occurs in 1-3% of women in the reproductive age group. Various factors such as anatomical, genetic and hormonal factors reported to influence PA. We report triple chromosomal abnormalities of rob(13;14(q10;q10,inv(9(p13q33, i(Xq(qter---q10::---qter in a case of PA and short stature. Though proband has multiple chromosome aberrations, genotypic effect of only i(Xq is evident as proband has PA and short stature. The rob(13;14 and inv(9, which are paternally derived may have role in later reproductive age. Therefore, chromosomal analysis is essential in such cases for the accurate diagnosis and management of the disease.

Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement.

Science.gov (United States)

Cordero, Mario D; Cano-García, Francisco Javier; Alcocer-Gómez, Elísabet; De Miguel, Manuel; Sánchez-Alcázar, José Antonio

2012-01-01

Fibromyalgia (FM) is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs) and its association to headache symptoms in FM patients. The effects of oral coenzyme Q(10) (CoQ(10)) supplementation on biochemical markers and clinical improvement were also evaluated. We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ), visual analogues scales (VAS), and the Headache Impact Test (HIT-6). Oxidative stress was determined by measuring CoQ(10), catalase and lipid peroxidation (LPO) levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. We found decreased CoQ(10), catalase and ATP levels in BMCs from FM patients as compared to normal control (P headache parameters were observed (r  = -0.59, P headache symptoms (P stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.

OleA Glu117 is key to condensation of two fatty-acyl coenzyme A substrates in long-chain olefin biosynthesis

Energy Technology Data Exchange (ETDEWEB)

Jensen, Matthew R.; Goblirsch, Brandon R.; Christenson, James K.; Esler, Morgan A.; Mohamed, Fatuma A.; Wackett, Lawrence P.; Wilmot, Carrie M. (UMM)

2017-10-12

In the interest of decreasing dependence on fossil fuels, microbial hydrocarbon biosynthesis pathways are being studied for renewable, tailored production of specialty chemicals and biofuels. One candidate is long-chain olefin biosynthesis, a widespread bacterial pathway that produces waxy hydrocarbons. Found in three- and four-gene clusters, oleABCD encodes the enzymes necessary to produce cis-olefins that differ by alkyl chain length, degree of unsaturation, and alkyl chain branching. The first enzyme in the pathway, OleA, catalyzes the Claisen condensation of two fatty acyl-coenzyme A (CoA) molecules to form a β-keto acid. In this report, the mechanistic role of Xanthomonas campestris OleA Glu117 is investigated through mutant enzymes. Crystal structures were determined for each mutant as well as their complex with the inhibitor cerulenin. Complemented by substrate modeling, these structures suggest that Glu117 aids in substrate positioning for productive carbon–carbon bond formation. Analysis of acyl-CoA substrate hydrolysis shows diminished activity in all mutants. When the active site lacks an acidic residue in the 117 position, OleA cannot form condensed product, demonstrating that Glu117 has a critical role upstream of the essential condensation reaction. Profiling of pH dependence shows that the apparent pKa for Glu117 is affected by mutagenesis. Taken together, we propose that Glu117 is the general base needed to prime condensation via deprotonation of the second, non-covalently bound substrate during turnover. This is the first example of a member of the thiolase superfamily of condensing enzymes to contain an active site base originating from the second monomer of the dimer.

Five Fatty Acyl-Coenzyme A Reductases Are Involved in the Biosynthesis of Primary Alcohols in Aegilops tauschii Leaves

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Meiling Wang

2017-06-01

Full Text Available The diploid Aegilops tauschii is the D-genome donor to hexaploid wheat (Triticum aestivum and represents a potential source for genetic study in common wheat. The ubiquitous wax covering the aerial parts of plants plays an important role in protecting plants against non-stomatal water loss. Cuticular waxes are complex mixtures of very-long-chain fatty acids, alkanes, primary and/or secondary alcohols, aldehydes, ketones, esters, triterpenes, sterols, and flavonoids. In the present work, primary alcohols were identified as the major components of leaf cuticular wax in Ae. tauschii, with C26:0-OH being the dominant primary alcohol. Analysis by scanning electron microscope revealed that dense platelet-shaped wax crystals were deposited on leaf surfaces of Ae. tauschii. Ten putative wax biosynthetic genes encoding fatty acyl-coenzyme A reductase (FAR were identified in the genome of Ae. tauschii. Five of these genes, Ae.tFAR1, Ae.tFAR2, Ae.tFAR3, Ae.tFAR4, and Ae.tFAR6, were found expressed in the leaf blades. Heterologous expression of the five Ae.tFARs in yeast (Saccharomyces cerevisiae showed that Ae.tFAR1, Ae.tFAR2, Ae.tFAR3, Ae.tFAR4, and Ae.tFAR6 were predominantly responsible for the accumulation of C16:0, C18:0, C26:0, C24:0, and C28:0 primary alcohols, respectively. In addition, nine Ae.tFAR paralogous genes were located on D chromosome of wheat and the wheat nullisomic–tetrasomic lines with the loss of Ae.tFAR3 and Ae.tFAR4 paralogous genes had significantly reduced levels of primary alcohols in the leaf blades. Collectively, these data suggest that Ae.tFAR1, Ae.tFAR2, Ae.tFAR3, Ae.tFAR4, and Ae.tFAR6 encode alcohol-forming FARs involved in the biosynthesis of primary alcohols in the leaf blades of Ae. tauschii. The information obtained in Ae. tauschii enables us to better understand wax biosynthesis in common wheat.

Chromosome 10q tetrasomy: First reported case

Energy Technology Data Exchange (ETDEWEB)

Blackston, R.D.; May, K.M.; Jones, F.D. [Emory Univ., Atlanta, GA (United States)] [and others

1994-09-01

While there are several reports of trisomy 10q (at least 35), we are not aware of previous cases of 10q tetrasomy. We present what we believe to be the initial report of such a case. R.J. is a 6 1/2 year old white male who presented with multiple dysmorphic features, marked articulation problems, hyperactivity, and developmental delays. He is the product of a term uncomplicated pregnancy. There was a normal spontaneous vaginal delivery with a birth weight of 6 lbs. 4oz. and length was 19 1/2 inch. Dysmorphic features include small size, an asymmetrically small head, low set ears with overfolded helixes, bilateral ptosis, downslanting eyes, right eye esotropia, prominent nose, asymmetric facies, high palate, mild pectus excavatum deformity of chest, and hyperextensible elbow joints. The patient is in special needs classes for mildly mentally handicapped students. Chromosome analysis at a resolution of 800 bands revealed a complex rearrangement of chromosomes 10 and 11. The segment 10q25.3 to q16.3 appears to be inverted and duplicated within the long arm of chromosome 10 at band q25.3 and the same segment of chromosome 10 is present on the terminal end of the short arm of chromosome 11. There is no visible loss of material from chromosome 11. Fluorescence in situ hybridization was performed with a chromosome 10 specific {open_quotes}paint{close_quotes} to confirm that all of the material on the abnormal 10 and the material on the terminal short arm of 11 was from chromosome 10. Thus, it appears that the segment 10q25.3 to q26.3 is present in four copies. Parental chromosome studies are normal. We compared findings which differ in that the case of 10q tetrasomy did not have prenatal growth deficiency, microphthalmia, cleft palate, digital anomalies, heart, or renal defects. Whereas most cases of 10q trisomy are said to have severe mental deficiency, our case of 10q tetrasomy was only mildly delayed. We report this first apparent cited case of 10q tetrasomy.

Coenzyme protection of lactic dehydrogenase against inactivation by gamma-rays

International Nuclear Information System (INIS)

Saito, M.

1978-01-01

A comparison has been made of the radiation sensitivities of the ternary complexes, oxamate-LDH-NADH and pyruvate-LDH-NAD with those of free LDH molecules and the intermediate binary complexes LDH-NAD and LDH-NADH. The enzyme solutions were 60 Co γirradiated and the rate of pyruvate reduction then measured. At doses of more than 10 krad the coenzymes afforded considerable protection to LDH against inactivation, and the dose-effect curves deviated from the curve for the unprotected enzyme, implying very specific protection. Coenzyme protection for a 30 krad dose at various concentrations of NAD and NADH reached a saturation level at about 4.0 x 10 -4 M for both NAD and NADH; protection by pyruvate alone was slight in comparison. Pyruvate and NAD (or oxamate and NADH) together at 1.0 x 10 -3 M protected the enzyme in a cooperative way. The results suggest that the major events of protection occur on the substrate and coenzyme binding sites, and support the view that coenzyme binding protects the enzyme by altering its conformation. (U.K.)

Biosynthesis of gold nanoparticles by actinomycete Streptomyces viridogens strain HM10.

Science.gov (United States)

Balagurunathan, R; Radhakrishnan, M; Rajendran, R Babu; Velmurugan, D

2011-10-01

Biosynthesis of gold nanoparticles by Streptomycetes from Himalayan Mountain was undertaken for the first time. Out of 10 actinomycete strains tested, four strains (D10, HM10, ANS2 and MSU) showed evidence for the intracellular biosynthesis of gold nanoparticles, among which the strain HM10 showed high potency. Presence of spherical and rod shaped gold nanoparticles in mycelium of the strain HM10 was determined by transmission electron microscopy (TEM) and X-ray diffraction analysis. The average particle size ranged from 18-20 nm. UV spectral analysis indicated that the reduction of chloroauric acid (HAuCl4) occurred within 24 h of reaction period. Further, the strain HM10 showed enhanced growth at 1 and 10 mM concentration of HAuCl4. The gold nanoparticles synthesized by the strain HM10 showed good antibacterial activity against S. aureus and E. coli in well-diffusion method. The potential actinomycete HM10 strain was phenotypically characterized and identified as Streptomyces viridogens (HM10). Thus, actinomycete strain HM10 reported in this study is a newly added source for the biosynthesis of gold nanoparticles.

Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q₁₀ effect on clinical improvement.

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Mario D Cordero

Full Text Available BACKGROUND: Fibromyalgia (FM is a chronic pain syndrome with unknown etiology and a wide spectrum of symptoms such as allodynia, debilitating fatigue, joint stiffness and migraine. Recent studies have shown some evidences demonstrating that oxidative stress is associated to clinical symptoms in FM of fibromyalgia. We examined oxidative stress and bioenergetic status in blood mononuclear cells (BMCs and its association to headache symptoms in FM patients. The effects of oral coenzyme Q(10 (CoQ(10 supplementation on biochemical markers and clinical improvement were also evaluated. METHODS: We studied 20 FM patients and 15 healthy controls. Clinical parameters were evaluated using the Fibromyalgia Impact Questionnaire (FIQ, visual analogues scales (VAS, and the Headache Impact Test (HIT-6. Oxidative stress was determined by measuring CoQ(10, catalase and lipid peroxidation (LPO levels in BMCs. Bioenergetic status was assessed by measuring ATP levels in BMCs. RESULTS: We found decreased CoQ(10, catalase and ATP levels in BMCs from FM patients as compared to normal control (P < 0.05 and P < 0.001, respectively We also found increased level of LPO in BMCs from FM patients as compared to normal control (P < 0.001. Significant negative correlations between CoQ(10 or catalase levels in BMCs and headache parameters were observed (r  = -0.59, P < 0.05; r  =  -0.68, P < 0.05, respectively. Furthermore, LPO levels showed a significant positive correlation with HIT-6 (r = 0.33, P<0.05. Oral CoQ(10 supplementation restored biochemical parameters and induced a significant improvement in clinical and headache symptoms (P < 0.001. DISCUSSION: The results of this study suggest a role for mitochondrial dysfunction and oxidative stress in the headache symptoms associated with FM. CoQ10 supplementation should be examined in a larger placebo controlled trial as a possible treatment in FM.

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy

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Gustavs Latkovskis

2016-01-01

Conclusions: Conifer-tree polyprenols in combination with CoQ10 may be generally safe in patients with SIM, but caution should be exercised in patients with glomerular filtration rate <60 mL/min and routine monitoring of the liver enzymes and CK is advocated in all patients. The observed efficacy provides the rationale for a larger, double-blind controlled study with polyprenols.

Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine.

Science.gov (United States)

Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew

2005-08-01

A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound

Systematic Analysis of the 4-Coumarate:Coenzyme A Ligase (4CL Related Genes and Expression Profiling during Fruit Development in the Chinese Pear

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Yunpeng Cao

2016-10-01

Full Text Available In plants, 4-coumarate:coenzyme A ligases (4CLs, comprising some of the adenylate-forming enzymes, are key enzymes involved in regulating lignin metabolism and the biosynthesis of flavonoids and other secondary metabolites. Although several 4CL-related proteins were shown to play roles in secondary metabolism, no comprehensive study on 4CL-related genes in the pear and other Rosaceae species has been reported. In this study, we identified 4CL-related genes in the apple, peach, yangmei, and pear genomes using DNATOOLS software and inferred their evolutionary relationships using phylogenetic analysis, collinearity analysis, conserved motif analysis, and structure analysis. A total of 149 4CL-related genes in four Rosaceous species (pear, apple, peach, and yangmei were identified, with 30 members in the pear. We explored the functions of several 4CL and acyl-coenzyme A synthetase (ACS genes during the development of pear fruit by quantitative real-time PCR (qRT-PCR. We found that duplication events had occurred in the 30 4CL-related genes in the pear. These duplicated 4CL-related genes are distributed unevenly across all pear chromosomes except chromosomes 4, 8, 11, and 12. The results of this study provide a basis for further investigation of both the functions and evolutionary history of 4CL-related genes.

Sperm FISH analysis of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat complex chromosome rearrangement.

Science.gov (United States)

Ferfouri, F; Boitrelle, F; Clement, P; Molina Gomes, D; Selva, J; Vialard, F

2014-06-01

Complex chromosome rearrangements (CCR) with two independent chromosome rearrangements are rare. Although CCRs lead to high unbalanced gamete rates, data on meiotic segregation in this context are scarce. A male patient was referred to our clinic as part of a family screening programme prompted by the observation of a 44,X,der(Y),t(Y;15)(q12;q10)pat,rob(13;14)(q10;q10)mat karyotype in his brother. Karyotyping identified the same CCR. Sperm FISH (with locus-specific probes for the segments involved in the translocations and nine chromosomes not involved in both rearrangements) was used to investigate the rearrangements meiotic segregation products and establish whether or not an inter-chromosomal effect was present. Sperm nuclear DNA fragmentation was also evaluated. For rob(13;14) and der(Y), the proportions of unbalanced products were, respectively, 26.4% and 60.6%. Overall, 70.3% of the meiotic segregation products were unbalanced. No evidence of an inter-chromosomal effect was found, and the sperm nuclear DNA fragmentation rate was similar to our laboratory's normal cut-off value. In view of previously published sperm FISH analyses of Robertsonian translocations (and even though the mechanism is still unknown), we hypothesise that cosegregation of der(Y) and rob(13;14) could modify rob(13;14) meiotic segregation. © 2013 Blackwell Verlag GmbH.

Effekt og sikkerhed af kosttilskud indeholdende Q10

DEFF Research Database (Denmark)

Overvad, O.K; Diamant, B; Holm, L

1997-01-01

The literature concerning the importance of Q10 for health and disease has been reviewed. Dietary intake together with normal in vivo synthesisseems to fulfil the body's demands for Q10 in younger, healthy individuals. The importance of Q10 in general well-being has not been investigated incontro...

Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

DEFF Research Database (Denmark)

Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

1992-01-01

Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

Synthesis, solution and crystal structure of the coenzyme B(12) analogue Co(β)-2'-fluoro-2',5'-dideoxyadenosylcobalamin.

Science.gov (United States)

Hunger, Miriam; Wurst, Klaus; Kräutler, Bernhard

2015-07-01

Crystal structure analyses have helped to decipher the mode of binding of coenzyme B12 (AdoCbl) in the active site of AdoCbl-dependent enzymes. However, the question of how such enzymes perform their radical reactions is still incompletely answered. A pioneering study by Gruber and Kratky of AdoCbl-dependent glutamate mutase (GLM) laid out a path for the movement of the catalytically active 5'-deoxyadenosyl radical, in which H-bonds between the protein and the 2'- and 3'-OH groups of the protein bound AdoCbl would play a decisive role. Studies with correspondingly modified coenzyme B12-analogues are of interest to gain insights into cofactor binding and enzyme mechanism. Here we report the preparation of Coβ-2'-fluoro-2',5'-dideoxyadenosylcobalamin (2'FAdoCbl), which lacks the 2'-OH group critical for the interaction in enzymes. 2'FAdoCbl was prepared by alkylation of cob(I)alamin, obtained from the electrochemical reduction of aquocobalamin. Spectroscopic data and a single crystal X-ray analysis of 2'FAdoCbl established its structure, which was very similar to that one of coenzyme B12. 2'FAdoCbl is a (19)F NMR active mimic of coenzyme B12 that may help to gain insights into binding interactions of coenzyme B12 with AdoCbl-dependent enzymes, proteins of B12 transport and of AdoCbl-biosynthesis, as well as with B12-riboswitches. Copyright © 2015 Elsevier Inc. All rights reserved.

Engineered Production of Short-Chain Acyl-Coenzyme A Esters in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Krink-Koutsoubelis, Nicolas; Loechner, Anne C.; Lechner, Anna

2018-01-01

Short-chain acyl-coenzyme A esters serve as intermediate compounds in fatty acid biosynthesis, and the production of polyketides, biopolymers and other value-added chemicals. S. cerevisiae is a model organism that has been utilized for the biosynthesis of such biologically and economically valuable...... compounds. However, its limited repertoire of short-chain acyl-CoAs effectively prevents its application as a production host for a plethora of natural products. Therefore, we introduced biosynthetic metabolic pathways to five different acyl-CoA esters into S. cerevisiae. Our engineered strains provide......-CoA at 0.5 μM; and isovaleryl-CoA, n-butyryl-CoA, and n-hexanoyl-CoA at 6 μM each. The acyl-CoAs produced in this study are common building blocks of secondary metabolites and will enable the engineered production of a variety of natural products in S. cerevisiae. By providing this toolbox of acyl...

Relatives with opposite chromosome constitutions, rec(10)dup(10p)inv(10)(p15.1q26.12) and rec(10)dup(10q)inv(10)(p15.1q26.12), due to a familial pericentric inversion.

Science.gov (United States)

Ciuladaite, Zivile; Preiksaitiene, Egle; Utkus, Algirdas; Kučinskas, Vaidutis

2014-01-01

Large pericentric inversions in chromosome 10 are rare chromosomal aberrations with only few cases of familial inheritance. Such chromosomal rearrangements may lead to production of unbalanced gametes. As a result of a recombination event in the inversion loop, 2 recombinants with duplicated and deficient chromosome segments, including the regions distal to the inversion, may be produced. We report on 2 relatives in a family with opposite terminal chromosomal rearrangements of chromosome 10, i.e. rec(10)dup(10p)inv(10) and rec(10)dup(10q)inv(10), due to familial pericentric inversion inv(10)(p15.1q26.12). Based on array-CGH results, we characterized the exact genomic regions involved and compared the clinical features of both patients with previous reports on similar pericentric inversions and regional differences within 10p and 10q. The fact that both products of recombination are viable indicates a potentially high recurrence risk of unbalanced offspring. This report of unbalanced rearrangements in chromosome 10 in 2 generations confirms the importance of screening for terminal imbalances in patients with idiopathic intellectual disability by molecular cytogenetic techniques such as FISH, MLPA or microarrays. It also underlines the necessity for FISH to define structural characteristics of such cryptic intrachromosomal rearrangements and the underlying cytogenetic mechanisms. © 2014 S. Karger AG, Basel.

No Effects of Antioxidant Supplementation in Triathletes on Maximal Oxygen Uptake, 31P-NMRS Detected Muscle Energy Metabolism and Muscle Fatigue

DEFF Research Database (Denmark)

Nielsen, A.N.; Mizuno, M.; Ratkevicius, Aivaras

1999-01-01

Antioxidative vitamins, coenzyme Q 10 electrical stimulation, isometric exercise, low frequency fatigue......Antioxidative vitamins, coenzyme Q 10 electrical stimulation, isometric exercise, low frequency fatigue...

Sesquiterpene Synthase-3-Hydroxy-3-Methylglutaryl Coenzyme A Synthase Fusion Protein Responsible for Hirsutene Biosynthesis in Stereum hirsutum.

Science.gov (United States)

Flynn, Christopher M; Schmidt-Dannert, Claudia

2018-06-01

The wood-rotting mushroom Stereum hirsutum is a known producer of a large number of namesake hirsutenoids, many with important bioactivities. Hirsutenoids form a structurally diverse and distinct class of sesquiterpenoids. No genes involved in hirsutenoid biosynthesis have yet been identified or their enzymes characterized. Here, we describe the cloning and functional characterization of a hirsutene synthase as an unexpected fusion protein of a sesquiterpene synthase (STS) with a C-terminal 3-hydroxy-3-methylglutaryl-coenzyme A (3-hydroxy-3-methylglutaryl-CoA) synthase (HMGS) domain. Both the full-length fusion protein and truncated STS domain are highly product-specific 1,11-cyclizing STS enzymes with kinetic properties typical of STSs. Complementation studies in Saccharomyces cerevisiae confirmed that the HMGS domain is also functional in vivo Phylogenetic analysis shows that the hirsutene synthase domain does not form a clade with other previously characterized sesquiterpene synthases from Basidiomycota. Comparative gene structure analysis of this hirsutene synthase with characterized fungal enzymes reveals a significantly higher intron density, suggesting that this enzyme may be acquired by horizontal gene transfer. In contrast, the HMGS domain is clearly related to other fungal homologs. This STS-HMGS fusion protein is part of a biosynthetic gene cluster that includes P450s and oxidases that are expressed and could be cloned from cDNA. Finally, this unusual fusion of a terpene synthase to an HMGS domain, which is not generally recognized as a key regulatory enzyme of the mevalonate isoprenoid precursor pathway, led to the identification of additional HMGS duplications in many fungal genomes, including the localization of HMGSs in other predicted sesquiterpenoid biosynthetic gene clusters. IMPORTANCE Hirsutenoids represent a structurally diverse class of bioactive sesquiterpenoids isolated from fungi. Identification of their biosynthetic pathways will provide

ROLE OF METABOLIC THERAPY IN TREATMENT OF MYOCARDIUM DYSTROPHY IN CHILDREN

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A.L. Frolenko

2010-01-01

Full Text Available The objective of present research was studying of influence of co-enzyme Q10 (Kudesan on cardiovascular system in children with myocardial dystrophy (MCD. Patients were divided on two comparable groups (n = 20 and n = 28 according to clinical symptoms of MCD, changes on electrocardiogram (ECG and results of echocardiography. Patients received non-drug means (massage, physical training in treatment regimen, psycho- and reflexotherapy and vasoactive, nootropic and sedative medications; patients from 2nd group were additionally treated with co-enzyme Q10 during 4 weeks. It was shown that inclusion of co-enzyme Q10 in complex treatment of MCD resulted in beneficial effect on self-feeling of child, favored to disappearance of repolarization disorders on ECG and increase of ejectional fraction. Thus, using of co-enzyme Q10 in complex treatment of children with MCD is reasonable. Key words: children, myocardial dystrophy, co-enzyme Q10, treatment.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2010;9(5:18-23

Role of Feedback Regulation of Pantothenate Kinase (CoaA) in Control of Coenzyme A Levels in Escherichia coli

Science.gov (United States)

Rock, Charles O.; Park, Hee-Won; Jackowski, Suzanne

2003-01-01

Pantothenate kinase (CoaA) is a key regulator of coenzyme A (CoA) biosynthesis in Escherichia coli, and its activity is controlled by feedback inhibition by CoA and its thioesters. The importance of feedback inhibition in the control of the intracellular CoA levels was tested by constructing three site-directed mutants of CoaA that were predicted to be feedback resistant based on the crystal structure of the CoaA-CoA binary complex. CoaA[R106A], CoaA[H177Q], and CoaA[F247V] were purified and shown to retain significant catalytic activity and be refractory to inhibition by CoA. CoaA[R106A] retained 50% of the catalytic activity of CoaA, whereas the CoaA[H177Q] and CoaA[F247V] mutants were less active. The importance of feedback control of CoaA to the intracellular CoA levels was assessed by expressing either CoaA or CoaA[R106A] in strain ANS3 [coaA15(Ts) panD2]. Cells expressing CoaA[R106A] had significantly higher levels of phosphorylated pantothenate-derived metabolites and CoA in vivo and excreted significantly more 4′-phosphopantetheine into the medium compared to cells expressing the wild-type protein. These data illustrate the key role of feedback regulation of pantothenate kinase in the control of intracellular CoA levels. PMID:12754240

Missionary Ethics in Q 10:2−12

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Dieter T. Roth

2012-06-01

Full Text Available Elements of the mission discourse of the Synoptic Gospels are found in Mark 6:6b−13; Matthew 9:35−10:15; Luke 9:1−6 and Luke 10:1−20. Similarities and differences in these accounts have led many New Testament scholars to posit the presence of a mission discourse in Q. This discourse, along with the parable that introduces it (Q 10:2, provides insight into how Q conceives of ‘mission’ as well as the ethical principles and precepts that are part of Jesus’ missional charge in this document. Through an intertextual approach to Q, with particular emphasis on narrative structure and imagery, this paper considered the interplay of mission and ethics in this early Christian text.

Skeletal muscle mitochondrial bioenergetics and associations with myostatin genotypes in the Thoroughbred horse.

Science.gov (United States)

Rooney, Mary F; Porter, Richard K; Katz, Lisa M; Hill, Emmeline W

2017-01-01

Variation in the myostatin (MSTN) gene has been reported to be associated with race distance, body composition and skeletal muscle fibre composition in the horse. The aim of the present study was to test the hypothesis that MSTN variation influences mitochondrial phenotypes in equine skeletal muscle. Mitochondrial abundance and skeletal muscle fibre types were measured in whole muscle biopsies from the gluteus medius of n = 82 untrained (21 ± 3 months) Thoroughbred horses. Skeletal muscle fibre type proportions were significantly (p T (C) and the SINE insertion 227 bp polymorphism (I). Evaluation of mitochondrial complex activities indicated higher combined mitochondrial complex I+III and II+III activities in the presence of the C-allele / I allele (p ≤ 0.05). The restoration of complex I+III and complex II+III activities following addition of exogenous coenzyme Q1 (ubiquinone1) (CoQ1) in vitro in the TT/NN (homozygous T allele/homozygous no insertion) cohort indicated decreased coenzyme Q in these animals. In addition, decreased gene expression in two coenzyme Q (CoQ) biosynthesis pathway genes (COQ4, p ≤ 0.05; ADCK3, p ≤ 0.01) in the TT/NN horses was observed. This study has identified several mitochondrial phenotypes associated with MSTN genotype in untrained Thoroughbred horses and in addition, our findings suggest that nutritional supplementation with CoQ may aid to restore coenzyme Q activity in TT/NN horses.

Comparative proteomic analysis provides insight into 10-hydroxy-2-decenoic acid biosynthesis in honey bee workers.

Science.gov (United States)

Yang, Xiao-Hui; Yang, Shi-Fa; Wang, Rui-Ming

2017-07-01

10-Hydroxy-2-decenoic acid (10-HDA) is the major compound produced from the mandibular glands (MGs) of honey bee workers. However, little information is available on the molecular mechanisms of 10-HDA biosynthesis. In our study, based on investigating the 10-HDA secretion pattern and the morphological characteristics of MGs from honey bee workers of different ages, a comparative proteomic analysis was performed in the MGs of workers with different 10-HDA production. In total, 59 up-regulated protein species representing 45 unique proteins were identified in high 10-HDA-producing workers by 2-DE-MALDI-TOF/TOF MS. These proteins were involved in carbohydrate/energy metabolism, fatty acid metabolism, protein metabolism and folding, antioxidation, cytoskeleton, development and cell signaling. Proteins related to fatty acid metabolism, including fatty acid synthase and β-oxidation enzymes, are potentially crucial proteins involved in 10-HDA biosynthesis pathway. And RNA interference (RNAi) results demonstrated that knockdown of electron transfer flavoprotein subunit beta (ETF-β), one of the protein related to fatty acid metabolism, decreased 10-HDA production of worker bees, suggesting that ETF-β was necessary for 10-HDA biosynthesis. This study reveals the characteristics of MGs of worker bees at different developmental stages and proteins associated with 10-HDA biosynthesis, which provides the first insight into the molecular mechanism of 10-HDA biosynthesis.

46,XY,DUP(10Q) IN DIRECT CVS PREPARATION AND MOSAIC 48,XXXY,DUP(10Q) IN CVS LONG-TERM CULTURE AND FETAL TISSUE

NARCIS (Netherlands)

SIJMONS, RH; SIKKEMARADDATZ, B; KLOOSTERMAN, MD; BRIET, JW; DEJONG, B; LESCHOT, NJ

Chorionic villus sampling (CVS) was performed on a 40-year-old woman at 9 1/2 menstrual weeks because of advanced maternal age. The direct preparation showed 46,XY,dup(10)(q11.2q23.2). CVS long-term culture and fetal tissue revealed a rare additional abnormality: 48,XXXY,dup(10)(q11.2q23.2). This

Současný pohled na koenzym Q

Czech Academy of Sciences Publication Activity Database

Rauchová, Hana; Vokurková, Martina

2009-01-01

Roč. 103, č. 1 (2009), s. 32-39 ISSN 0009-2770 R&D Projects: GA MŠk(CZ) 1M0510 Institutional research plan: CEZ:AV0Z50110509 Keywords : coenzyme Q * mitochondria * dietary supplement Subject RIV: CE - Biochemistry Impact factor: 0.717, year: 2009

CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues

Directory of Open Access Journals (Sweden)

Sarah A. Abd El-Aal

2017-10-01

Full Text Available Statins were reported to lower the Coenzyme Q10 (CoQ10 content upon their inhibition of HMG-CoA reductase enzyme and both are known to possess neuroprotective potentials; therefore, the aim is to assess the possible use of CoQ10 as an adds-on therapy to rosuvastatin to improve its effect using global I/R model. Rats were allocated into sham, I/R, rosuvastatin (10 mg/kg, CoQ10 (10 mg/kg and their combination. Drugs were administered orally for 7 days before I/R. Pretreatment with rosuvastatin and/or CoQ10 inhibited the hippocampal content of malondialdehyde, nitric oxide, and boosted glutathione and superoxide dismutase. They also opposed the upregulation of gp91phox, and p47phox subunits of NADPH oxidase. Meanwhile, both agents reduced content/expression of TNF-α, iNOS, NF-κBp65, ICAM-1, and MPO. Besides, all regimens abated cytochrome c, caspase-3 and Bax, but increased Bcl-2 in favor of cell survival. On the molecular level, they increased p-Akt and its downstream target p-FOXO3A, with the inhibition of the nuclear content of FOXO3A to downregulate the expression of Bim, a pro-apoptotic gene. Additionally, both treatments downregulate the JNK3/c-Jun signaling pathway. The effect of the combination regimen overrides that of either treatment alone. These effects were reflected on the alleviation of the hippocampal damage in CA1 region inflicted by I/R. Together, these findings accentuate the neuroprotective potentials of both treatments against global I/R by virtue of their rigorous multi-pronged actions, including suppression of hippocampal oxidative stress, inflammation, and apoptosis with the involvement of the Akt/FOXO3A/Bim and JNK3/c-Jun/Bax signaling pathways. The study also nominates CoQ10 as an adds-on therapy with statins.

Syntenic homology of human unique DNA sequences within chromossome regions 5q31, 10q22, 13q32-33 and 19q13.1 in the great apes

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Rhea U. Vallente-Samonte

2000-09-01

Full Text Available Homologies between chromosome banding patterns and DNA sequences in the great apes and humans suggest an apparent common origin for these two lineages. The availability of DNA probes for specific regions of human chromosomes (5q31, 10q22, 13q32-33 and 19q13.1 led us to cross-hybridize these to chimpanzee (Pan troglodytes, PTR, gorilla (Gorilla gorilla, GGO and orangutan (Pongo pygmaeus, PPY chromosomes in a search for equivalent regions in the great apes. Positive hybridization signals to the chromosome 5q31-specific DNA probe were observed at HSA 5q31, PTR 4q31, GGO 4q31 and PPY 4q31, while fluorescent signals using the chromosome 10q22-specific DNA probe were noted at HSA 10q22, PTR 8q22, GGO 8q22 and PPY 7q22. The chromosome arms showing hybridization signals to the Quint-EssentialTM 13-specific DNA probe were identified as HSA 13q32-33, PTR 14q32-33, GGO 14q32-33 and PPY 14q32-33, while those presenting hybridization signals to the chromosome 19q13.1-specific DNA probe were identified as HSA 19q13.1, PTR 20q13, GGO 20q13 and PPY 20q13. All four probes presumably hybridized to homologous chromosomal locations in the apes, which suggests a homology of certain unique DNA sequences among hominoid species.Homologias entre os padrões de bandamento de cromossomos e seqüências de DNA em grandes macacos e humanos sugerem uma aparente origem comum para estas duas linhagens. A disponibilidade de sondas de DNA para regiões específicas de cromossomos humanos (5q31, 10q22, 13q32-33 e 19q13.1 nos levou a realizar hibridação cruzada com cromossomos de chimpanzé (Pan troglodytes, PTR, gorila (Gorilla gorilla, GGO e orangotango (Pongo pygmaeus, PPY em um pesquisa de regiões equivalentes em grandes macacos. Sinais positivos de hibridação para a sonda de DNA específica para o cromossomo 5q31 foram observados em HSA 5q31, PTR 4q31, GGO 4q31 e PPY 4q31, enquanto que sinais fluorescentes usando a sonda de DNA específica para o cromossomo 10q22 foram

The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the δT-cell receptor with TCL3, a conserved and activated locus at 10q24

International Nuclear Information System (INIS)

Zutter, M.; Hockett, R.D.; Roberts, C.W.M.; McGuire, E.A.; Bloomstone, J.; Korsmeyer, S.J.; Morton, C.C.; Deaven, L.L.; Crist, W.M.; Carroll, A.J.

1990-01-01

The authors cloned the t(10;14) recurrent translocation from CD3-negative T-cell acute lymphoblastic leukemia cells. The breakpoint at 14q11 involved an intermediate rearrangement of the δ T-cell receptor locus, suggesting that the translocation arose at the time of antigen receptor assemblage. Translocation introduced chromosome segment 10q24 as proven by hybridization of a breakpoint-derived probe to flow-sorted chromosomes and metaphase chromosomes. Two t(10;14) breakpoints were clustered within a 600-base-pair region of 10q24 but no heptamer-spacer-nonamer motifs resembling T-cell receptor/immunoglobulin rearrangement signals were noted at the breakpoint. A locus distinct from terminal deoxynucleotidyltransferase was found at 10q24. Evolutionarily conserved regions surrounding the 10q24 breakpoint were examined for transcriptional activity. A region telomeric to the 10q24 breakpoint, expected to translocate to the der(14) chromosome, recognized an abundant 2.9-kilobase RNA in a t(10;14) T-cell leukemia. This locus was not active in a variety of other normal and neoplastic T cells, arguing that it was deregulated by he introduction of the T-cell receptor. This locus is a candidate for a putative protooncogene, TCL3, involved in T-cell neoplasia

Radical S-adenosylmethionine (SAM) enzymes in cofactor biosynthesis: a treasure trove of complex organic radical rearrangement reactions.

Science.gov (United States)

Mehta, Angad P; Abdelwahed, Sameh H; Mahanta, Nilkamal; Fedoseyenko, Dmytro; Philmus, Benjamin; Cooper, Lisa E; Liu, Yiquan; Jhulki, Isita; Ealick, Steven E; Begley, Tadhg P

2015-02-13

In this minireview, we describe the radical S-adenosylmethionine enzymes involved in the biosynthesis of thiamin, menaquinone, molybdopterin, coenzyme F420, and heme. Our focus is on the remarkably complex organic rearrangements involved, many of which have no precedent in organic or biological chemistry. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Anthocyanin biosynthesis in pears is regulated by a R2R3-MYB transcription factor PyMYB10.

Science.gov (United States)

Feng, Shouqian; Wang, Yanling; Yang, Song; Xu, Yuting; Chen, Xuesen

2010-06-01

Skin color is an important factor in pear breeding programs. The degree of red coloration is determined by the content and composition of anthocyanins. In plants, many MYB transcriptional factors are involved in regulating anthocyanin biosynthesis. In this study, a R2R3-MYB transcription factor gene, PyMYB10, was isolated from Asian pear (Pyrus pyrifolia) cv. 'Aoguan'. Sequence analysis suggested that the PyMYB10 gene was an ortholog of MdMYB10 gene, which regulates anthocyanin biosynthesis in red fleshed apple (Malus x domestica) cv. 'Red Field'. PyMYB10 was identified at the genomic level and had three exons, with its upstream sequence containing core sequences of cis-acting regulatory elements involved in light responsiveness. Fruit bagging showed that light could induce expression of PyMYB10 and anthocyanin biosynthesis. Quantitative real-time PCR revealed that PyMYB10 was predominantly expressed in pear skins, buds, and young leaves, and the level of transcription in buds was higher than in skin and young leaves. In ripening fruits, the transcription of PyMYB10 in the skin was positively correlated with genes in the anthocyanin pathway and with anthocyanin biosynthesis. In addition, the transcription of PyMYB10 and genes of anthocyanin biosynthesis were more abundant in red-skinned pear cultivars compared to blushed cultivars. Transgenic Arabidopsis plants overexpressing PyMYB10 exhibited ectopic pigmentation in immature seeds. The study suggested that PyMYB10 plays a role in regulating anthocyanin biosynthesis and the overexpression of PyMYB10 was sufficient to induce anthocyanin accumulation.

AarF Domain Containing Kinase 3 (ADCK3 Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation.

Directory of Open Access Journals (Sweden)

Jason K Cullen

Full Text Available Autosomal recessive ataxias are a clinically diverse group of syndromes that in some cases are caused by mutations in genes with roles in the DNA damage response, transcriptional regulation or mitochondrial function. One of these ataxias, known as Autosomal Recessive Cerebellar Ataxia Type-2 (ARCA-2, also known as SCAR9/COQ10D4; OMIM: #612016, arises due to mutations in the ADCK3 gene. The product of this gene (ADCK3 is an atypical kinase that is thought to play a regulatory role in coenzyme Q10 (CoQ10 biosynthesis. Although much work has been performed on the S. cerevisiae orthologue of ADCK3, the cellular and biochemical role of its mammalian counterpart, and why mutations in this gene lead to human disease is poorly understood. Here, we demonstrate that ADCK3 localises to mitochondrial cristae and is targeted to this organelle via the presence of an N-terminal localisation signal. Consistent with a role in CoQ10 biosynthesis, ADCK3 deficiency decreased cellular CoQ10 content. In addition, endogenous ADCK3 was found to associate in vitro with recombinant Coq3, Coq5, Coq7 and Coq9, components of the CoQ10 biosynthetic machinery. Furthermore, cell lines derived from ARCA-2 patients display signs of oxidative stress, defects in mitochondrial homeostasis and increases in lysosomal content. Together, these data shed light on the possible molecular role of ADCK3 and provide insight into the cellular pathways affected in ARCA-2 patients.

KUDESAN EFFICACY IN ADOLESCENTS WITH METABOLIC SYNDROME

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M.B. Kolesnikova

2011-01-01

Full Text Available Metabolic abnormalities in metabolic syndrome affect the functioning of practically all organs and systems, and most seriously — cardio-vascular system. Cardio-vascular abnormalities in metabolic syndrome manifest as arterial hypertension, Riley-Day syndrome and endothelial dysfunction that can lead to decrease of adaptive and reserve capabilities. Co-enzyme Q10 possesses cardioprotective,  stress-protective and anti-ischaemic activity. Clinical study performed on 40 children aged 10 to 17 years with constitutive obesity, complicated metabolic syndrome, has proven validity of co-enzyme Q10 treatment in patients with metabolic syndrome. The use of co-enzyme Q10 15 mg/day during 30 days has lead to improvement of psycho-emotional condition, decrease in anxiety complaints, sleep improvement, decrease in asthenic syndrome symptoms, improvement in electrophysiological heart indices Key words: metabolic syndrome, co-enzyme Q10. (Voprosy sovremennoi pediatrii — Current Pediatrics. — 2011; 10 (5: 102–106.

Muscle Fibre Types, Ubiquinone Content and Exercise Capacity in Hypertension and Effort Angina

DEFF Research Database (Denmark)

Karlsson, Jan; Diamant, Bertil; Folkers, Karl

1991-01-01

Farmakologi, hypertension, IHD, skeletal muscle fibre composition, muscle coenzyme Q10, ischaemic heart disease, effort angina, muscle fibre lesion, muscle ubiquinone......Farmakologi, hypertension, IHD, skeletal muscle fibre composition, muscle coenzyme Q10, ischaemic heart disease, effort angina, muscle fibre lesion, muscle ubiquinone...

FAR5, a fatty acyl-coenzyme A reductase, is involved in primary alcohol biosynthesis of the leaf blade cuticular wax in wheat (Triticum aestivum L.).

Science.gov (United States)

Wang, Yong; Wang, Meiling; Sun, Yulin; Wang, Yanting; Li, Tingting; Chai, Guaiqiang; Jiang, Wenhui; Shan, Liwei; Li, Chunlian; Xiao, Enshi; Wang, Zhonghua

2015-03-01

A waxy cuticle that serves as a protective barrier against non-stomatal water loss and environmental damage coats the aerial surfaces of land plants. It comprises a cutin polymer matrix and waxes. Cuticular waxes are complex mixtures of very long chain fatty acids (VLCFAs) and their derivatives. Results show that primary alcohols are the major components of bread wheat (Triticum aestivum L.) leaf blade cuticular waxes. Here, the characterization of TaFAR5 from wheat cv Xinong 2718, which is allelic to TAA1b, an anther-specific gene, is reported. Evidence is presented for a new function for TaFAR5 in the biosynthesis of primary alcohols of leaf blade cuticular wax in wheat. Expression of TaFAR5 cDNA in yeast (Saccharomyces cerevisiae) led to production of C22:0 primary alcohol. The transgenic expression of TaFAR5 in tomato (Solanum lycopersicum) cv MicroTom leaves resulted in the accumulation of C26:0, C28:0, and C30:0 primary alcohols. TaFAR5 encodes an alcohol-forming fatty acyl-coenzyme A reductase (FAR). Expression analysis revealed that TaFAR5 was expressed at high levels in the leaf blades, anthers, pistils, and seeds. Fully functional green fluorescent protein-tagged TaFAR5 protein was localized to the endoplasmic reticulum (ER), the site of primary alcohol biosynthesis. SDS-PAGE analysis indicated that the TaFAR5 protein possessed a molecular mass of 58.4kDa, and it was also shown that TaFAR5 transcript levels were regulated in response to drought, cold, and abscisic acid (ABA). Overall, these data suggest that TaFAR5 plays an important role in the synthesis of primary alcohols in wheat leaf blade. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.

Science.gov (United States)

Tan, J; Tay, J S; Wong, Y C; Kham, S K; Bte Abd Aziz, N; Teo, S H; Wong, H B

1995-01-01

Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.

7Q10 flows for SRS streams

International Nuclear Information System (INIS)

Chen, K.F.

1996-01-01

The Environmental Transport Group of the Environmental Technology Section was requested to predict the seven-day ten-year low flow (7Q10 flow) for the SRS streams based on historical stream flow records. Most of the historical flow records for the SRS streams include reactor coolant water discharged from the reactors and process water released from the process facilities. The most straight forward way to estimate the stream daily natural flow is to subtract the measured upstream reactor and/or facility daily effluents from the measured downstream daily flow. Unfortunately, this method does not always work, as indicated by the fact that sometimes the measured downstream volumetric flow rates are lower than the reactor effluent volumetric flow rates. For those cases that cannot be analyzed with the simple subtracting method, an alternative method was used to estimate the stream natural flows by statistically separating reactor coolant and process water flow data. The correlation between the calculated 7Q10 flows and the watershed areas for Four Mile Branch and Pen Branch agrees with that calculated by the USGS for Upper Three Runs and Lower Three Runs Creeks. The agreement between these two independent calculations lends confidence to the 7Q10 flow calculations presented in this report

Biosynthesis of the major tetrahydroxystilbenes in spruce, astringin and isorhapontin, proceeds via resveratrol and is enhanced by fungal infection.

Science.gov (United States)

Hammerbacher, Almuth; Ralph, Steven G; Bohlmann, Joerg; Fenning, Trevor M; Gershenzon, Jonathan; Schmidt, Axel

2011-10-01

Stilbenes are dibenzyl polyphenolic compounds produced in several unrelated plant families that appear to protect against various biotic and abiotic stresses. Stilbene biosynthesis has been well described in economically important plants, such as grape (Vitis vinifera), peanut (Arachis hypogaea), and pine (Pinus species). However, very little is known about the biosynthesis and ecological role of stilbenes in spruce (Picea), an important gymnosperm tree genus in temperate and boreal forests. To investigate the biosynthesis of stilbenes in spruce, we identified two similar stilbene synthase (STS) genes in Norway spruce (Picea abies), PaSTS1 and PaSTS2, which had orthologs with high sequence identity in sitka (Picea sitchensis) and white (Picea glauca) spruce. Despite the conservation of STS sequences in these three spruce species, they differed substantially from angiosperm STSs. Several types of in vitro and in vivo assays revealed that the P. abies STSs catalyze the condensation of p-coumaroyl-coenzyme A and three molecules of malonyl-coenzyme A to yield the trihydroxystilbene resveratrol but do not directly form the dominant spruce stilbenes, which are tetrahydroxylated. However, in transgenic Norway spruce overexpressing PaSTS1, significantly higher amounts of the tetrahydroxystilbene glycosides, astringin and isorhapontin, were produced. This result suggests that the first step of stilbene biosynthesis in spruce is the formation of resveratrol, which is further modified by hydroxylation, O-methylation, and O-glucosylation to yield astringin and isorhapontin. Inoculating spruce with fungal mycelium increased STS transcript abundance and tetrahydroxystilbene glycoside production. Extracts from STS-overexpressing lines significantly inhibited fungal growth in vitro compared with extracts from control lines, suggesting that spruce stilbenes have a role in antifungal defense.

Radioprotection of DNA molecule by oxido-reduction's coenzymes

International Nuclear Information System (INIS)

Araos, M.S.; Fernandez, M.; Tomicic, I.; Toha, J.C.

1978-01-01

The radio protective action of respiratory coenzymes on DNA-water solutions is studied after irradiation with a 60 Co source. Coenzymes were used separately or in mixtures of their oxidized and reduced forms. The dose relative factor (DRF) values evaluated by uv absorbancy measurements of DNA damage were high: 18.03 for the (NAD-FAD-quinone) mixture (a respiratory chain model); 14.91 for (quinone-hydroquinone) mixtures; 14.46 for quinone; 14.27 for hydroquinone; 12.49 for FAD; 7.21 for the (NAD-NADH) mixture; 6.48 for NADH and 3.79 for NAD. No parallelism was found between the DNA coenzymes strong interactions and their protective action, performed by overcoming the indirect radiation damage. Besides, uv irradiation studies give no support to protection through direct energy transfer processes from excited DNA to coenzymes. The high efficiency of the mixtures of oxidized-reduced respiratory coenzymes is discussed in terms of simultaneous and equivalent trapping of recombinable radicals. The high tolerance of these protectors in living cells is emphasized. (author)

Conserved Lipid and Small-Molecule Modulation of COQ8 Reveals Regulation of the Ancient Kinase-like UbiB Family.

Science.gov (United States)

Reidenbach, Andrew G; Kemmerer, Zachary A; Aydin, Deniz; Jochem, Adam; McDevitt, Molly T; Hutchins, Paul D; Stark, Jaime L; Stefely, Jonathan A; Reddy, Thiru; Hebert, Alex S; Wilkerson, Emily M; Johnson, Isabel E; Bingman, Craig A; Markley, John L; Coon, Joshua J; Dal Peraro, Matteo; Pagliarini, David J

2018-02-15

Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activity in vivo. Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates. We further create an analog-sensitive version of Coq8p and reveal that acute chemical inhibition of its endogenous activity in yeast is sufficient to cause respiratory deficiency concomitant with CoQ depletion. Collectively, this work defines lipid and small-molecule modulators of an ancient family of atypical kinase-like proteins and establishes a chemical genetic system for further exploring the mechanistic role of COQ8 in CoQ biosynthesis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Autism spectrum disorder with microdeletion 10q26 by subtelomere FISH

Directory of Open Access Journals (Sweden)

Tonk VS

2011-05-01

Full Text Available Vijay S Tonk1,2, Golder N Wilson11Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock, TX, USA; 2Departments of Pathology, Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, TX, USAAbstract: An 11-year-old female with early feeding problems, mild motor delays, normal speech, subtle facial changes, social difficulties, anxiety and a diagnosis of Asperger disorder was found to have deletion of 10q26.3 by subtelomere fluorescent in situ hybridization (stF analysis. Our patient and others with 10q26 aneuploidy add this region to 11 other autism susceptibility loci qualified by converging genome linkage/association, high resolution chromosome, and mutation studies in our review. We summarize these loci and the current spectrum of terminal 10q deletion cases.Keywords: autism disorder, Asperger disorder, subtelomere FISH, microarray analysis, 10q26 deletion, gene changes in autism

Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function

OpenAIRE

Fonseca, Luis Vazquez; Doimo, Mara; Calderan, Cristina; Desbats, Maria Andrea; Acosta, Manuel J.; Cerqua, Cristina; Cassina, Matteo; Ashraf, Shazia; Hildebrandt, Friedhelm; Sartori, Geppo; Navas, Placido; Trevisson, Eva; Salviati, Leonardo

2018-01-01

Abstract Mutations in COQ8B cause steroid‐resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix protein peripherally associated with the inner membrane. COQ8B can complement a ΔCOQ8 yeast strain when its mitochondrial targeting sequenc...

Chemistry and Molecular Dynamics Simulations of Heme b-HemQ and Coproheme-HemQ.

Science.gov (United States)

Hofbauer, Stefan; Dalla Sega, Marco; Scheiblbrandner, Stefan; Jandova, Zuzana; Schaffner, Irene; Mlynek, Georg; Djinović-Carugo, Kristina; Battistuzzi, Gianantonio; Furtmüller, Paul G; Oostenbrink, Chris; Obinger, Christian

2016-09-27

Recently, a novel pathway for heme b biosynthesis in Gram-positive bacteria has been proposed. The final poorly understood step is catalyzed by an enzyme called HemQ and includes two decarboxylation reactions leading from coproheme to heme b. Coproheme has been suggested to act as both substrate and redox active cofactor in this reaction. In the study presented here, we focus on HemQs from Listeria monocytogenes (LmHemQ) and Staphylococcus aureus (SaHemQ) recombinantly produced as apoproteins in Escherichia coli. We demonstrate the rapid and two-phase uptake of coproheme by both apo forms and the significant differences in thermal stability of the apo forms, coproheme-HemQ and heme b-HemQ. Reduction of ferric high-spin coproheme-HemQ to the ferrous form is shown to be enthalpically favored but entropically disfavored with standard reduction potentials of -205 ± 3 mV for LmHemQ and -207 ± 3 mV for SaHemQ versus the standard hydrogen electrode at pH 7.0. Redox thermodynamics suggests the presence of a pronounced H-bonding network and restricted solvent mobility in the heme cavity. Binding of cyanide to the sixth coproheme position is monophasic but relatively slow (∼1 × 10(4) M(-1) s(-1)). On the basis of the available structures of apo-HemQ and modeling of both loaded forms, molecular dynamics simulation allowed analysis of the interaction of coproheme and heme b with the protein as well as the role of the flexibility at the proximal heme cavity and the substrate access channel for coproheme binding and heme b release. Obtained data are discussed with respect to the proposed function of HemQ in monoderm bacteria.

Enabling ICH Q10 Implementation--Part 1. Striving for Excellence by Embracing ICH Q8 and ICH Q9.

Science.gov (United States)

Calnan, Nuala; O'Donnell, Kevin; Greene, Anne

2013-01-01

This article is the first in a series of articles that will focus on understanding the implementation essentials necessary to deliver operational excellence through a International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q10-based pharmaceutical quality system (PQS). The authors examine why, despite the fact that the ICH Q10 guideline has been with us since 2008, the transformation of the traditional Quality Management Systems QMS in use within the pharmaceutical industry is a work in progress for only a few forward-thinking organisations. Unfortunately, this transformation remains a mere aspiration for the majority of organisations. We explore the apparent lack of progress by the pharmaceutical sector in adopting six sigma and related quality management techniques to ensure the availability of high-quality medicines worldwide. The authors propose that the desired progress can be delivered through two key shifts in our current practices; by embodying the principles of operational excellence in every aspect of our business and by learning how to unlock the scientific and tacit knowledge within our organisations. It has been ten years since The Wall Street Journal revealed the pharmaceutical industry's "little secret" comparing the perceived level of manufacturing expertise in the industry as lagging far behind those of potato-chip and laundry-soap makers. Would you consider the quality and manufacturing strategies in place today in your organisation to be more efficient and scientifically based than those of 2003? If so, what evidence exists for you to draw any conclusion regarding enhanced performance? Do your current practices drive innovation and facilitate continual improvement and if so, how? Ultimately, can you confidently affirm that patient-related risks associated with the product(s) manufactured by your organisation have been reduced due to the quality assurance program now applied

STATINS AND MYOPATHY: MOLECULAR MECHANISMS

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O. M. Drapkina

2012-01-01

Full Text Available The safety of statin therapy is considered. In particular the reasons of a complication such as myopathy are discussed in detail. The molecular mechanisms of statin myopathy , as well as its risk factors are presented. The role of coenzyme Q10 in the myopathy development and coenzyme Q10 application for the prevention of this complication are considered. 

Thermophilic Coenzyme B12-Dependent Acyl Coenzyme A (CoA) Mutase from Kyrpidia tusciae DSM 2912 Preferentially Catalyzes Isomerization of (R)-3-Hydroxybutyryl-CoA and 2-Hydroxyisobutyryl-CoA.

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Weichler, Maria-Teresa; Kurteva-Yaneva, Nadya; Przybylski, Denise; Schuster, Judith; Müller, Roland H; Harms, Hauke; Rohwerder, Thore

2015-07-01

The recent discovery of a coenzyme B12-dependent acyl-coenzyme A (acyl-CoA) mutase isomerizing 3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in the mesophilic bacterium Aquincola tertiaricarbonis L108 (N. Yaneva, J. Schuster, F. Schäfer, V. Lede, D. Przybylski, T. Paproth, H. Harms, R. H. Müller, and T. Rohwerder, J Biol Chem 287:15502-15511, 2012, http://dx.doi.org/10.1074/jbc.M111.314690) could pave the way for a complete biosynthesis route to the building block chemical 2-hydroxyisobutyric acid from renewable carbon. However, the enzyme catalyzes only the conversion of the stereoisomer (S)-3-hydroxybutyryl-CoA at reasonable rates, which seriously hampers an efficient combination of mutase and well-established bacterial poly-(R)-3-hydroxybutyrate (PHB) overflow metabolism. Here, we characterize a new 2-hydroxyisobutyryl-CoA mutase found in the thermophilic knallgas bacterium Kyrpidia tusciae DSM 2912. Reconstituted mutase subunits revealed highest activity at 55°C. Surprisingly, already at 30°C, isomerization of (R)-3-hydroxybutyryl-CoA was about 7,000 times more efficient than with the mutase from strain L108. The most striking structural difference between the two mutases, likely determining stereospecificity, is a replacement of active-site residue Asp found in strain L108 at position 117 with Val in the enzyme from strain DSM 2912, resulting in a reversed polarity at this binding site. Overall sequence comparison indicates that both enzymes descended from different prokaryotic thermophilic methylmalonyl-CoA mutases. Concomitant expression of PHB enzymes delivering (R)-3-hydroxybutyryl-CoA (beta-ketothiolase PhaA and acetoacetyl-CoA reductase PhaB from Cupriavidus necator) with the new mutase in Escherichia coli JM109 and BL21 strains incubated on gluconic acid at 37°C led to the production of 2-hydroxyisobutyric acid at maximal titers of 0.7 mM. Measures to improve production in E. coli, such as coexpression of the chaperone MeaH and repression of

Coenzyme Q10: Can It Prevent Statin Side Effects?

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Vitamin K2 biosynthetic enzyme, UBIAD1 is essential for embryonic development of mice.

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Nakagawa, Kimie; Sawada, Natsumi; Hirota, Yoshihisa; Uchino, Yuri; Suhara, Yoshitomo; Hasegawa, Tomoka; Amizuka, Norio; Okamoto, Tadashi; Tsugawa, Naoko; Kamao, Maya; Funahashi, Nobuaki; Okano, Toshio

2014-01-01

UbiA prenyltransferase domain containing 1 (UBIAD1) is a novel vitamin K2 biosynthetic enzyme screened and identified from the human genome database. UBIAD1 has recently been shown to catalyse the biosynthesis of Coenzyme Q10 (CoQ10) in zebrafish and human cells. To investigate the function of UBIAD1 in vivo, we attempted to generate mice lacking Ubiad1, a homolog of human UBIAD1, by gene targeting. Ubiad1-deficient (Ubiad1(-/-)) mouse embryos failed to survive beyond embryonic day 7.5, exhibiting small-sized body and gastrulation arrest. Ubiad1(-/-) embryonic stem (ES) cells failed to synthesize vitamin K2 but were able to synthesize CoQ9, similar to wild-type ES cells. Ubiad1(+/-) mice developed normally, exhibiting normal growth and fertility. Vitamin K2 tissue levels and synthesis activity were approximately half of those in the wild-type, whereas CoQ9 tissue levels and synthesis activity were similar to those in the wild-type. Similarly, UBIAD1 expression and vitamin K2 synthesis activity of mouse embryonic fibroblasts prepared from Ubiad1(+/-) E15.5 embryos were approximately half of those in the wild-type, whereas CoQ9 levels and synthesis activity were similar to those in the wild-type. Ubiad1(-/-) mouse embryos failed to be rescued, but their embryonic lifespans were extended to term by oral administration of MK-4 or CoQ10 to pregnant Ubiad1(+/-) mice. These results suggest that UBIAD1 is responsible for vitamin K2 synthesis but may not be responsible for CoQ9 synthesis in mice. We propose that UBIAD1 plays a pivotal role in embryonic development by synthesizing vitamin K2, but may have additional functions beyond the biosynthesis of vitamin K2.

A chromosome 10 variant with a 12 Mb inversion [inv(10)(q11.22q21.1)] identical by descent and frequent in the Swedish population.

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Entesarian, Miriam; Carlsson, Birgit; Mansouri, Mahmoud Reza; Stattin, Eva-Lena; Holmberg, Eva; Golovleva, Irina; Stefansson, Hreinn; Klar, Joakim; Dahl, Niklas

2009-03-01

We identified a paracentric inversion of chromosome 10 [inv(10)(q11.22q21.1)] in 0.20% of Swedish individuals (15/7,439) referred for cytogenetic analysis. A retrospective analysis of 8,896 karyotypes from amniocenteses in Sweden revealed a carrier frequency of 0.079% (7/8,896) for the inversion. Cloning and detailed analysis of the inversion breakpoint regions show enrichment for interspersed repeat elements and AT-stretches. The centromeric breakpoint coincides with that of a predicted inversion from HapMap data, which suggests that this region is involved in several chromosome 10 variants. No known gene or predicted transcript are disrupted by the inversion which spans approximately 12 Mb. Carriers from four non-related Swedish families have identical inversion breakpoints and haplotype analysis confirmed that the rearrangement is identical by descent. Diagnosis was retrieved in 6 out of the 15 carriers referred for cytogenetic analysis. No consistent phenotype was found to be associated with the inversion. Our study demonstrates that the inv(10)(q11.22q21.1) is a rare and inherited chromosome variant with a broad geographical distribution in Sweden. 2009 Wiley-Liss, Inc.

Arg279 is the key regulator of coenzyme selectivity in the flavin-dependent ornithine monooxygenase SidA.

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Robinson, Reeder; Franceschini, Stefano; Fedkenheuer, Michael; Rodriguez, Pedro J; Ellerbrock, Jacob; Romero, Elvira; Echandi, Maria Paulina; Martin Del Campo, Julia S; Sobrado, Pablo

2014-04-01

Siderophore A (SidA) is a flavin-dependent monooxygenase that catalyzes the NAD(P)H- and oxygen-dependent hydroxylation of ornithine in the biosynthesis of siderophores in Aspergillus fumigatus and is essential for virulence. SidA can utilize both NADPH or NADH for activity; however, the enzyme is selective for NADPH. Structural analysis shows that R279 interacts with the 2'-phosphate of NADPH. To probe the role of electrostatic interactions in coenzyme selectivity, R279 was mutated to both an alanine and a glutamate. The mutant proteins were active but highly uncoupled, oxidizing NADPH and producing hydrogen peroxide instead of hydroxylated ornithine. For wtSidA, the catalytic efficiency was 6-fold higher with NADPH as compared to NADH. For the R279A mutant the catalytic efficiency was the same with both coenyzmes, while for the R279E mutant the catalytic efficiency was 5-fold higher with NADH. The effects are mainly due to an increase in the KD values, as no major changes on the kcat or flavin reduction values were observed. Thus, the absence of a positive charge leads to no coenzyme selectivity while introduction of a negative charge leads to preference for NADH. Flavin fluorescence studies suggest altered interaction between the flavin and NADP⁺ in the mutant enzymes. The effects are caused by different binding modes of the coenzyme upon removal of the positive charge at position 279, as no major conformational changes were observed in the structure for R279A. The results indicate that the positive charge at position 279 is critical for tight binding of NADPH and efficient hydroxylation. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of a Plasmodium falciparum Orthologue of the Yeast Ubiquinone-Binding Protein, Coq10p.

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Bethany J Jenkins

Full Text Available Coenzyme Q (CoQ, ubiquinone is a central electron carrier in mitochondrial respiration. CoQ is synthesized through multiple steps involving a number of different enzymes. The prevailing view that the CoQ used in respiration exists as a free pool that diffuses throughout the mitochondrial inner membrane bilayer has recently been challenged. In the yeast Saccharomyces cerevisiae, deletion of the gene encoding Coq10p results in respiration deficiency without inhibiting the synthesis of CoQ, suggesting that the Coq10 protein is critical for the delivery of CoQ to the site(s of respiration. The precise mechanism by which this is achieved remains unknown at present. We have identified a Plasmodium orthologue of Coq10 (PfCoq10, which is predominantly expressed in trophozoite-stage parasites, and localizes to the parasite mitochondrion. Expression of PfCoq10 in the S. cerevisiae coq10 deletion strain restored the capability of the yeast to grow on respiratory substrates, suggesting a remarkable functional conservation of this protein over a vast evolutionary distance, and despite a relatively low level of amino acid sequence identity. As the antimalarial drug atovaquone acts as a competitive inhibitor of CoQ, we assessed whether over-expression of PfCoq10 altered the atovaquone sensitivity in parasites and in yeast mitochondria, but found no alteration of its activity.

A Boy with an LCR3/4-Flanked 10q22.3q23.2 Microdeletion and Uncommon Phenotypic Features

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Petrova, E.; Neuner, C.; Haaf, T.; Schmid, M.; Wirbelauer, J.; Jurkutat, A.; Wermke, K.; Nanda, I.; Kunstmann, E.

2014-01-01

The recurrent 10q22.3q23.2 deletion with breakpoints within low copy repeats 3 and 4 is a rare genomic disorder, reported in only 13 patients to date. The phenotype is rather uncharacteristic, which makes a clinical diagnosis difficult. A phenotypic feature described in almost all patients is a delay in speech development, albeit systematic studies are still pending. In this study, we report on a boy with an LCR3/4-flanked 10q22.3q23.2 deletion exhibiting an age-appropriate language development evaluated by a standardized test at an age of 2 years and 3 months. The boy was born with a cleft palate – a feature not present in any of the patients described before. Previously reported cases are reviewed, and the role of the BMPR1A gene is discussed. The phenotype of patients with an LCR3/4-flanked 10q22.3q23.2 deletion can be rather variable, so counseling the families regarding the prognosis of an affected child should be done with caution. Long-term studies of affected children are needed to delineate the natural history of this rare disorder. PMID:24550761

Elucidation of the mechanism of atorvastatin-induced myopathy in a rat model.

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El-Ganainy, Samar O; El-Mallah, Ahmed; Abdallah, Dina; Khattab, Mahmoud M; Mohy El-Din, Mahmoud M; El-Khatib, Aiman S

2016-06-01

Myopathy is among the well documented and the most disturbing adverse effects of statins. The underlying mechanism is still unknown. Mitochondrial dysfunction related to coenzyme Q10 decline is one of the proposed theories. The present study aimed to investigate the mechanism of atorvastatin-induced myopathy in rats. In addition, the mechanism of the coenzyme Q10 protection was investigated with special focus of mitochondrial alterations. Sprague-Dawely rats were treated orally either with atorvastatin (100mg/kg) or atorvastatin and coenzyme Q10 (100mg/kg). Myopathy was assessed by measuring serum creatine kinase (CK) and myoglobin levels together with examination of necrosis in type IIB fiber muscles. Mitochondrial dysfunction was evaluated by measuring muscle lactate/pyruvate ratio, ATP level, pAkt as well as mitochondrial ultrastructure examination. Atorvastatin treatment resulted in a rise in both CK (2X) and myoglobin (6X) level with graded degrees of muscle necrosis. Biochemical determinations showed prominent increase in lactate/pyruvate ratio and a decline in both ATP (>80%) and pAkt (>50%) levels. Ultrastructure examination showed mitochondrial swelling with disrupted organelle membrane. Co-treatment with coenzyme Q10 induced reduction in muscle necrosis as well as in CK and myoglobin levels. In addition, coenzyme Q10 improved all mitochondrial dysfunction parameters including mitochondrial swelling and disruption. These results presented a model for atorvastatin-induced myopathy in rats and proved that mitochondrial dysfunction is the main contributor in statin-myopathy pathophysiology. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

UbiX is a flavin prenyltransferase required for bacterial ubiquinone biosynthesis

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White, Mark D.; Payne, Karl A.P.; Fisher, Karl; Marshall, Stephen A.; Parker, David; Rattray, Nicholas J.W.; Trivedi, Drupad K.; Goodacre, Royston; Rigby, Stephen E.J.; Scrutton, Nigel S.; Hay, Sam; Leys, David

2016-01-01

Ubiquinone, or coenzyme Q, is a ubiquitous lipid-soluble redox cofactor that is an essential component of electron transfer chains1. Eleven genes have been implicated in bacterial ubiquinone biosynthesis, including ubiX and ubiD, which are responsible for decarboxylation of the 3-octaprenyl-4-hydroxybenzoate precursor2. Despite structural and biochemical characterization of UbiX as an FMN-binding protein, no decarboxylase activity has been detected3–4. We report here that UbiX produces a novel flavin-derived cofactor required for the decarboxylase activity of UbiD5. UbiX acts as a flavin prenyltransferase, linking a dimethylallyl moiety to the flavin N5 and C6 atoms. This adds a fourth non-aromatic ring to the flavin isoalloxazine group. In contrast to other prenyltransferases6–7, UbiX is metal-independent and requires dimethylallyl-monophosphate as substrate. Kinetic crystallography reveals that the prenyl transferase mechanism of UbiX resembles that of the terpene synthases8. The active site environment is dominated by π-systems, which assist phosphate-C1’ bond breakage following FMN reduction, leading to formation of the N5-C1’ bond. UbiX then acts as a chaperone for adduct reorientation, via transient carbocation species, leading ultimately to formation of the dimethylallyl C3’-C6 bond. The study establishes the mechanism for formation of a new flavin-derived cofactor, extending both flavin and terpenoid biochemical repertoire. PMID:26083743

Thermodynamics of various F420 coenzyme models as sources of electrons, hydride ions, hydrogen atoms and protons in acetonitrile.

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Xia, Ke; Shen, Guang-Bin; Zhu, Xiao-Qing

2015-06-14

32 F420 coenzyme models with alkylation of the three different N atoms (N1, N3 and N10) in the core structure (XFH(-)) were designed and synthesized and the thermodynamic driving forces (defined in terms of the molar enthalpy changes or the standard redox potentials in this work) of the 32 XFH(-) releasing hydride ions, hydrogen atoms and electrons, the thermodynamic driving forces of the 32 XFH˙ releasing protons and hydrogen atoms and the thermodynamic driving forces of XF(-)˙ releasing electrons in acetonitrile were determined using titration calorimetry and electrochemical methods. The effects of the methyl group at N1, N3 and N10 and a negative charge on N1 and N10 atoms on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were examined; the results show that seating arrangements of the methyl group and the negative charge have remarkably different effects on the thermodynamic properties of the F420 coenzyme models and their related reaction intermediates. The effects of the substituents at C7 and C8 on the six thermodynamic driving forces of the F420 coenzyme models and their related reaction intermediates were also examined; the results show that the substituents at C7 and C8 have good Hammett linear free energy relationships with the six thermodynamic parameters. Meanwhile, a reasonable determination of possible reactions between members of the F420 family and NADH family in vivo was given according to a thermodynamic analysis platform constructed using the elementary step thermodynamic parameter of F420 coenzyme model 2FH(-) and NADH model MNAH releasing hydride ions in acetonitrile. The information disclosed in this work can not only fill a gap in the chemical thermodynamics of F420 coenzyme models as a class of very important organic sources of electrons, hydride ions, hydrogen atoms and protons, but also strongly promote the fast development of the chemistry and applications of F420 coenzyme.

Cofilin/Twinstar phosphorylation levels increase in response to impaired coenzyme a metabolism.

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Katarzyna Siudeja

Full Text Available Coenzyme A (CoA is a pantothenic acid-derived metabolite essential for many fundamental cellular processes including energy, lipid and amino acid metabolism. Pantothenate kinase (PANK, which catalyses the first step in the conversion of pantothenic acid to CoA, has been associated with a rare neurodegenerative disorder PKAN. However, the consequences of impaired PANK activity are poorly understood. Here we use Drosophila and human neuronal cell cultures to show how PANK deficiency leads to abnormalities in F-actin organization. Cells with reduced PANK activity are characterized by abnormally high levels of phosphorylated cofilin, a conserved actin filament severing protein. The increased levels of phospho-cofilin coincide with morphological changes of PANK-deficient Drosophila S2 cells and human neuronal SHSY-5Y cells. The latter exhibit also markedly reduced ability to form neurites in culture--a process that is strongly dependent on actin remodeling. Our results reveal a novel and conserved link between a metabolic biosynthesis pathway, and regulation of cellular actin dynamics.

Does a General Temperature-Dependent Q10 Model of Soil Respiration Exist at Biome and Global Scale?

Institute of Scientific and Technical Information of China (English)

Hua CHEN; Han-Qin TIAN

2005-01-01

Soil respiration (SR) is commonly modeled by a Q10 (an indicator of temperature sensitivity)function in ecosystem models. Q10is usually treated as a constant of 2 in these models, although Q10 value of SR often decreases with increasing temperatures. It remains unclear whether a general temperaturedependent Q10 model of SR exists at biome and global scale. In this paper, we have compiled the long-term Q10 data of 38 SR studies ranging from the Boreal, Temperate, to Tropical/Subtropical biome on four continents.Our analysis indicated that the general temperature-dependent biome Q10 models of SR existed, especially in the Boreal and Temperate biomes. A single-exponential model was better than a simple linear model in fitting the average Q10 values at the biome scale. Average soil temperature is a better predictor of Q10 value than average air temperature in these models, especially in the Boreal biome. Soil temperature alone could explain about 50% of the Q10 variations in both the Boreal and Temperate biome single-exponential Q10 model. Q10 value of SR decreased with increasing soil temperature but at quite different rates among the three biome Q10 models. The k values (Q10 decay rate constants) were 0.09, 0.07, and 0.02/℃ in the Boreal, Temperate, and Tropical/Subtropical biome, respectively, suggesting that Q10 value is the most sensitive to soil temperature change in the Boreal biome, the second in the Temperate biome, and the least sensitive in the Tropical/Subtropical biome. This also indirectly confirms that acclimation of SR in many soil warming experiments probably occurs. The k value in the "global" single-exponential Q10 model which combined both the Boreal and Temperate biome data set was 0.08/℃. However, the global general temperature-dependent Q10model developed using the data sets of the three biomes is not adequate for predicting Q10 values of SR globally.The existence of the general temperature-dependent Q10 models of SR in the Boreal and

In Vivo Roles of Fatty Acid Biosynthesis Enzymes in Biosynthesis of Biotin and α-Lipoic Acid in Corynebacterium glutamicum.

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Ikeda, Masato; Nagashima, Takashi; Nakamura, Eri; Kato, Ryosuke; Ohshita, Masakazu; Hayashi, Mikiro; Takeno, Seiki

2017-10-01

For fatty acid biosynthesis, Corynebacterium glutamicum uses two type I fatty acid synthases (FAS-I), FasA and FasB, in addition to acetyl-coenzyme A (CoA) carboxylase (ACC) consisting of AccBC, AccD1, and AccE. The in vivo roles of the enzymes in supplying precursors for biotin and α-lipoic acid remain unclear. Here, we report genetic evidence demonstrating that the biosynthesis of these cofactors is linked to fatty acid biosynthesis through the FAS-I pathway. For this study, we used wild-type C. glutamicum and its derived biotin vitamer producer BFI-5, which was engineered to express Escherichia coli bioBF and Bacillus subtilis bioI Disruption of either fasA or fasB in strain BFI-5 led to decreased production of biotin vitamers, whereas its amplification contributed to increased production, with a larger impact of fasA in both cases. Double disruptions of fasA and fasB resulted in no biotin vitamer production. The acc genes showed a positive effect on production when amplified simultaneously. Augmented fatty acid biosynthesis was also reflected in pimelic acid production when carbon flow was blocked at the BioF reaction. These results indicate that carbon flow down the FAS-I pathway is destined for channeling into the biotin biosynthesis pathway, and that FasA in particular has a significant impact on precursor supply. In contrast, fasB disruption resulted in auxotrophy for lipoic acid or its precursor octanoic acid in both wild-type and BFI-5 strains. The phenotypes were fully complemented by plasmid-mediated expression of fasB but not fasA These results reveal that FasB plays a specific physiological role in lipoic acid biosynthesis in C. glutamicum IMPORTANCE For the de novo biosynthesis of fatty acids, C. glutamicum exceptionally uses a eukaryotic multifunctional type I fatty acid synthase (FAS-I) system comprising FasA and FasB, in contrast to most bacteria, such as E. coli and B. subtilis , which use an individual nonaggregating type II fatty acid synthase

ApoB-100 secretion by HepG2 cells is regulated by the rate of triglyceride biosynthesis but not by intracellular lipid pools.

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Benoist, F; Grand-Perret, T

1996-10-01

Triglycerides (TGs), cholesteryl esters (CEs), cholesterol, and phosphatidylcholine have been independently proposed as playing regulatory roles in apoB-100 secretion; the results depended on the cellular model used. In this study, we reinvestigate the role of lipids in apoB-100 production in HepG2 cells and in particular, we clarify the respective roles of intracellular mass and the biosynthesis of lipids in the regulation of apoB-100 production. In a first set of experiments, the pool size of cholesterol, CEs, and TGs was modulated by a 3-day treatment with either lipid precursors or inhibitors of enzymes involved in lipid synthesis. We used simvastatin (a hydroxymethylglutaryl coenzyme A reductase inhibitor), 58-035 (an acyl coenzyme A cholesterol acyltransferase inhibitor), 5-tetradecyloxy-2-furancarboxylic acid (TOFA, an inhibitor of fatty acid synthesis), and oleic acid. The secretion rate of apoB-100 was not affected by the large modulation of lipid mass induced by these various pre-treatments. In a second set of experiments, the same lipid modulators were added during a 4-hour labeling period. Simvastatin and 58-035 inhibited cholesterol and CE synthesis without affecting apoB-100 secretion. By contrast, treatment of HepG2 cells with TOFA resulted in the inhibition of TG synthesis and apoB-100 secretion. This effect was highly specific for apoB-100 and was reversed by adding oleic acid, which stimulated both TG synthesis and apoB-100 secretion. Moreover, a combination of oleic acid and 58-035 inhibited CE biosynthesis and increased both TG synthesis and apoB-100 secretion. These results show that in HepG2 cells TG biosynthesis regulates apoB-100 secretion, whereas the rate of cholesterol or CE biosynthesis has no effect.

Regulation of protein biosynthesis by non-lymphoid cells requires the participation of receptors, which recognize the same protein through a center analogous to the antibody active center

International Nuclear Information System (INIS)

Kul'berg, A.Y.; Ivanovska, N.D.; Tarkhanova, I.A.

1986-01-01

This paper studies the mechanism for regulating the biosynthesis of one of the complement components (anti-idiotypic antibodies CI /SUB q/ ) by macrophages. The experiments were conducted on mouse resident peritoneal macrophages cultivated in medium containing C 14-glycine. The synthesis of CI /SUB q/ was evaluated according to the content of protein which was bound by rabbit antibodies against mouse CI /SUB q/ immobilized on bromocyan-Sepharose 4B. The study of the kinetics of the biosynthesis of CI /SUB q/ by propagated macrophages shows that the biosynthesis was initially recorded and in the subsequent period the culture contained no other cells apart from macrophages

Temperature-related changes in respiration and Q10 coefficient of Guava

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Bron Ilana Urbano

2005-01-01

Full Text Available Guava (Psidium guajava L. is a tropical fruit that presents fast post-harvest ripening; therefore it is a very perishable product. Inappropriate storage temperature and retail practices can accelerate fruit quality loss. The objective of this study was to evaluate the respiratory activity (RA, the ethylene production (EP and Q10 of guava fruit at different storage temperatures. 'Paluma' guava fruits were harvested at maturity stage 1 (dark-green skin and stored at either 1, 11, 21, 31 or 41ºC; RA and EP were determined after 12, 36, 84 and 156 h of storage. RA and EP rates at 1 and 11ºC were the lowest - 0.16 and 0.43 mmol CO2 kg-1 h-1 and 0.003 and 0.019 µmol C2H4 kg-1 h-1, respectively. When guavas were stored at 21ºC, a gradual increase occurred in RA and EP, reaching 2.24 mmol CO2 kg-1 h-1 and 0.20 µmol C2H4 kg-1 h-1, after 156 h of storage. The highest RA and EP were recorded for guavas stored at 31ºC. In spite of high RA, guavas stored at 41ºC presented EP similar to guavas stored at 11ºC, an indicator of heat-stress injury. Considering the 1-11ºC range, the mean Q10 value was around 3.0; the Q10 value almost duplicated at 11-21ºC range (5.9. At 21-31ºC and 31-41ºC, Q10 was 1.5 and 0.8, respectively. Knowing Q10, respiratory variation and ripening behavior in response to different temperatures, fruit storage and retail conditions can be optimized to reduce quality losses.

Protein Engineering for Nicotinamide Coenzyme Specificity in Oxidoreductases: Attempts and Challenges.

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Chánique, Andrea M; Parra, Loreto P

2018-01-01

Oxidoreductases are ubiquitous enzymes that catalyze an extensive range of chemical reactions with great specificity, efficiency, and selectivity. Most oxidoreductases are nicotinamide cofactor-dependent enzymes with a strong preference for NADP or NAD. Because these coenzymes differ in stability, bioavailability and costs, the enzyme preference for a specific coenzyme is an important issue for practical applications. Different approaches for the manipulation of coenzyme specificity have been reported, with different degrees of success. Here we present various attempts for the switching of nicotinamide coenzyme preference in oxidoreductases by protein engineering. This review covers 103 enzyme engineering studies from 82 articles and evaluates the accomplishments in terms of coenzyme specificity and catalytic efficiency compared to wild type enzymes of different classes. We analyzed different protein engineering strategies and related them with the degree of success in inverting the cofactor specificity. In general, catalytic activity is compromised when coenzyme specificity is reversed, however when switching from NAD to NADP, better results are obtained. In most of the cases, rational strategies were used, predominantly with loop exchange generating the best results. In general, the tendency of removing acidic residues and incorporating basic residues is the strategy of choice when trying to change specificity from NAD to NADP, and vice versa . Computational strategies and algorithms are also covered as helpful tools to guide protein engineering strategies. This mini review aims to give a general introduction to the topic, giving an overview of tools and information to work in protein engineering for the reversal of coenzyme specificity.

The Antibiotic CJ-15,801 is an Antimetabolite which Hijacks and then Inhibits CoA Biosynthesis

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van der Westhuyzen, Renier; Hammons, Justin C.; Meier, Jordan L.; Dahesh, Samira; Moolman, Wessel J. A.; Pelly, Stephen C.; Nizet, Victor; Burkart, Michael D.; Strauss, Erick

2012-01-01

SUMMARY The natural product CJ-15,801 is an inhibitor of Staphylococcus aureus, but not other bacteria. Its close structural resemblance to pantothenic acid, the vitamin precursor of coenzyme A (CoA), and its Michael acceptor moiety suggest that it irreversibly inhibits an enzyme involved in CoA biosynthesis or utilization. However, its mode of action and the basis for its specificity have not been elucidated to date. We demonstrate that CJ-15,801 is transformed by the uniquely selective S. aureus pantothenate kinase, the first CoA biosynthetic enzyme, into a substrate for the next enzyme, phosphopantothenoylcysteine synthetase, which is inhibited through formation of a tight-binding structural mimic of its native reaction intermediate. These findings reveal CJ-15,801 as a vitamin biosynthetic pathway antimetabolite with a mechanism similar to that of the sulfonamide antibiotics, and highlight CoA biosynthesis as a viable antimicrobial drug target. PMID:22633408

Simvastatin effects on skeletal muscle

DEFF Research Database (Denmark)

Larsen, Steen; Stride, Nis; Hey-Mogensen, Martin

2013-01-01

Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9)....

Biosynthesis of oleamide.

Science.gov (United States)

Mueller, Gregory P; Driscoll, William J

2009-01-01

Oleamide (cis-9-octadecenamide) is the prototype long chain primary fatty acid amide lipid messenger. The natural occurrence of oleamide was first reported in human serum in 1989. Subsequently oleamide was shown to accumulate in the cerebrospinal fluid of sleep-deprived cats and to induce sleep when administered to experimental animals. Accordingly, oleamide first became known for its potential role in the mechanisms that mediate the drive to sleep. Oleamide also has profound effects on thermoregulation and acts as an analgesic in several models of experimental pain. Although these important pharmacologic effects are well establish, the biochemical mechanism for the synthesis of oleamide has not yet been defined. This chapter reviews the biosynthetic pathways that have been proposed and highlights two mechanisms which are most supported by experimental evidence: the generation of oleamide from oleoylglycine by the neuropeptide processing enzyme, peptidylglycine alpha-amidating monooxygenase (PAM), and alternatively, the direct amidation of oleic acid via oleoyl coenzyme A by cytochrome c using ammonia as the nitrogen source. The latter mechanism is discussed in the context of apoptosis where oleamide may play a role in regulating gap junction communication. Lastly, several considerations and caveats pertinent to the future study oleamide biosynthesis are discussed.

Synthesis of complex intermediates for the study of a dehydratase from borrelidin biosynthesis

Directory of Open Access Journals (Sweden)

Frank Hahn

2014-03-01

Full Text Available Herein, we describe the syntheses of a complex biosynthesis-intermediate analogue of the potent antitumor polyketide borrelidin and of reference molecules to determine the stereoselectivity of the dehydratase of borrelidin polyketide synthase module 3. The target molecules were obtained from a common precursor aldehyde in the form of N-acetylcysteamine (SNAc thioesters and methyl esters in 13 to 15 steps. Key steps for the assembly of the polyketide backbone of the dehydratase substrate analogue were a Yamamoto asymmetric carbocyclisation and a Sakurai allylation as well as an anti-selective aldol reaction. Reference compounds representing the E- and Z-configured double bond isomers as potential products of the dehydratase reaction were obtained from a common precursor aldehyde by Wittig olefination and Still–Gennari olefination. The final deprotection of TBS ethers and methyl esters was performed under mildly acidic conditions followed by pig liver esterase-mediated chemoselective hydrolysis. These conditions are compatible with the presence of a coenzyme A or a SNAc thioester, suggesting that they are generally applicable to the synthesis of complex polyketide-derived thioesters suited for biosynthesis studies.

Spermicidal and contraceptive properties of azauirachtin-A on rats and the possible amelioration effects of some antioxidants on their sexual efficiency

International Nuclear Information System (INIS)

Hebashy, M.I.A.; Mazen, G.M.A.; Amer, M.M.

2006-01-01

This investigation was conducted to evaluate the spermicidal properties of azadirachtin-A to immobilize (in male) and kill (in female) spermatozoa of rats. Also, the ability of coenzyme Q10 or taurine or their mixture to improve anti-fertility action of azadirachtin-A and to ameliorate perturbation in fertility of normal rats. The obtained results revealed that normal sperms, testosterone, testis and ovary GSH and GPx, estradiol and progesterone were declined significantly in azadirachtin-A rats. On the other hand, azadirachtin-A caused significant elevation in the total number of abnormal sperm, sperm malformed head or tail, head and tail and serum lipid peroxidation (malonaldehyde) in comparison to the normal control rats. The administration of coenzyme Q10 or taurine led to correction in all previous parameters and the maximum ameliorating effects were exhibited in the rats treated with the mixture of coenzyme Q10 and taurine depending on certain mechanisms

Genes involved in long-chain alkene biosynthesis in Micrococcus luteus.

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Beller, Harry R; Goh, Ee-Been; Keasling, Jay D

2010-02-01

Aliphatic hydrocarbons are highly appealing targets for advanced cellulosic biofuels, as they are already predominant components of petroleum-based gasoline and diesel fuels. We have studied alkene biosynthesis in Micrococcus luteus ATCC 4698, a close relative of Sarcina lutea (now Kocuria rhizophila), which 4 decades ago was reported to biosynthesize iso- and anteiso-branched, long-chain alkenes. The underlying biochemistry and genetics of alkene biosynthesis were not elucidated in those studies. We show here that heterologous expression of a three-gene cluster from M. luteus (Mlut_13230-13250) in a fatty acid-overproducing Escherichia coli strain resulted in production of long-chain alkenes, predominantly 27:3 and 29:3 (no. carbon atoms: no. C=C bonds). Heterologous expression of Mlut_13230 (oleA) alone produced no long-chain alkenes but unsaturated aliphatic monoketones, predominantly 27:2, and in vitro studies with the purified Mlut_13230 protein and tetradecanoyl-coenzyme A (CoA) produced the same C(27) monoketone. Gas chromatography-time of flight mass spectrometry confirmed the elemental composition of all detected long-chain alkenes and monoketones (putative intermediates of alkene biosynthesis). Negative controls demonstrated that the M. luteus genes were responsible for production of these metabolites. Studies with wild-type M. luteus showed that the transcript copy number of Mlut_13230-13250 and the concentrations of 29:1 alkene isomers (the dominant alkenes produced by this strain) generally corresponded with bacterial population over time. We propose a metabolic pathway for alkene biosynthesis starting with acyl-CoA (or-ACP [acyl carrier protein]) thioesters and involving decarboxylative Claisen condensation as a key step, which we believe is catalyzed by OleA. Such activity is consistent with our data and with the homology (including the conserved Cys-His-Asn catalytic triad) of Mlut_13230 (OleA) to FabH (beta-ketoacyl-ACP synthase III), which

Expression profiles of genes involved in tanshinone biosynthesis of ...

Indian Academy of Sciences (India)

Expression profiles of genes involved in tanshinone biosynthesis of two. Salvia miltiorrhiza genotypes with different tanshinone contents. Zhenqiao Song, Jianhua Wang and Xingfeng Li. J. Genet. 95, 433–439. Table 1. S. miltiorrhiza genes and primer pairs used for qRT-PCR. Gene. GenBank accession. Primer name.

Coenzyme Q10 Deficiency and Type 2C Muscle Fibers

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J Gordon Millichap

2013-12-01

Full Text Available Investigators at Washington University School of Medicine, St Louis, MO, evaluated retrospectively clinical, laboratory, and muscle histochemistry and oxidative enzyme characteristics in 49 children with suspected mitochondrial disorders.

Neutral lipid biosynthesis in engineered Escherichia coli: jojoba oil-like wax esters and fatty acid butyl esters.

Science.gov (United States)

Kalscheuer, Rainer; Stöveken, Tim; Luftmann, Heinrich; Malkus, Ursula; Reichelt, Rudolf; Steinbüchel, Alexander

2006-02-01

Wax esters are esters of long-chain fatty acids and long-chain fatty alcohols which are of considerable commercial importance and are produced on a scale of 3 million tons per year. The oil from the jojoba plant (Simmondsia chinensis) is the main biological source of wax esters. Although it has a multitude of potential applications, the use of jojoba oil is restricted, due to its high price. In this study, we describe the establishment of heterologous wax ester biosynthesis in a recombinant Escherichia coli strain by coexpression of a fatty alcohol-producing bifunctional acyl-coenzyme A reductase from the jojoba plant and a bacterial wax ester synthase from Acinetobacter baylyi strain ADP1, catalyzing the esterification of fatty alcohols and coenzyme A thioesters of fatty acids. In the presence of oleate, jojoba oil-like wax esters such as palmityl oleate, palmityl palmitoleate, and oleyl oleate were produced, amounting to up to ca. 1% of the cellular dry weight. In addition to wax esters, fatty acid butyl esters were unexpectedly observed in the presence of oleate. The latter could be attributed to solvent residues of 1-butanol present in the medium component, Bacto tryptone. Neutral lipids produced in recombinant E. coli were accumulated as intracytoplasmic inclusions, demonstrating that the formation and structural integrity of bacterial lipid bodies do not require specific structural proteins. This is the first report on substantial biosynthesis and accumulation of neutral lipids in E. coli, which might open new perspectives for the biotechnological production of cheap jojoba oil equivalents from inexpensive resources employing recombinant microorganisms.

Genome-Wide Identification and Comparative Analysis of the 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (HMGR Gene Family in Gossypium

Directory of Open Access Journals (Sweden)

Wei Liu

2018-01-01

Full Text Available Terpenes are the largest and most diverse class of secondary metabolites in plants and play a very important role in plant adaptation to environment. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGR is a rate-limiting enzyme in the process of terpene biosynthesis in the cytosol. Previous study found the HMGR genes underwent gene expansion in Gossypium raimondii, but the characteristics and evolution of the HMGR gene family in Gossypium genus are unclear. In this study, genome-wide identification and comparative study of HMGR gene family were carried out in three Gossypium species with genome sequences, i.e., G. raimondii, Gossypium arboreum, and Gossypium hirsutum. In total, nine, nine and 18 HMGR genes were identified in G. raimondii, G. arboreum, and G. hirsutum, respectively. The results indicated that the HMGR genes underwent gene expansion and a unique gene cluster containing four HMGR genes was found in all the three Gossypium species. The phylogenetic analysis suggested that the expansion of HMGR genes had occurred in their common ancestor. There was a pseudogene that had a 10-bp deletion resulting in a frameshift mutation and could not be translated into functional proteins in G. arboreum and the A-subgenome of G. hirsutum. The expression profiles of the two pseudogenes showed that they had tissue-specific expression. Additionally, the expression pattern of the pseudogene in the A-subgenome of G. hirsutum was similar to its paralogous gene in the D-subgenome of G. hirsutum. Our results provide useful information for understanding cytosolic terpene biosynthesis in Gossypium species.

Distal trisomy 10q syndrome, report of a patient with duplicated q24.31 – qter, autism spectrum disorder and unusual features

Science.gov (United States)

Al-Sarraj, Yasser; Al-Khair, Hakam Abu; Taha, Rowaida Ziad; Khattab, Namat; El Sayed, Zakaria H; Elhusein, Bushra; El-Shanti, Hatem

2014-01-01

Key Clinical Message We report on a patient with distal trisomy 10q syndrome presenting with a few previously undescribed physical features, as well as, autism spectrum disorder (ASD). We recommend that patients with distal trisomy 10q syndrome should have a behavioral evaluation for ASD for the early institution of therapy. PMID:25614812

Is Co Q10 really valuable in shielding statin induced myopathy-an exploration

International Nuclear Information System (INIS)

Noor, M.; Waheed, A.; Muhammad, I; Bakhtiar, S.

2016-01-01

Objective: This study was designed to scrutinize the shielding effects of Co enzyme Q10 (Co Q10) supplementation in statin associated muscular adverse effects in rabbits. Study Design: Randomized controlled trial. Place and Duration of Study: Pharmacology dept Army Medical College Rawalpindi from Jan 2012 to Jun 2012. Material and Methods: Twenty two healthy rabbits were taken and divided into four equal groups randomly with six in each batch. The two groups (G1 and G2) were given toxic doses of simvastatin (60mg/kg/day) with and without Co Q10 (5mg/kg/day) orally for 14 days and rest of two groups (G3 and G4) were kept on therapeutic doses (1mg/kg/day) of simvastatin with and without Co Q10 (5mg/kg/day) orally for 90 days. Blood samples were drawn and serum creatinine kinase (CK) and lactate dehydrogenase (LDH) were assessed before and after the drug therapy. Histopathological examination was done to observe the inflammatory changes under light microscope. The results were analyzed by applying paired 't' test, independent 't' test and ANOVA test for biochemical markers and 'Chi-Square test' for histopathological findings. The p-value < 0.05 was considered significant. Results: The biochemical markers went up sharply (G1. CK=28899.5 +- 874.09 IU/L and LDH = 4694.33 +- 352 IU/L) and (G2. CK = 29191.33 +- 3019.79 IU/L and LDH = 4334.83 +- 143.44 IU/L) as compared to baseline values. They were given toxic doses of simvastatin with and without Co Q10. Histopathological examination of muscular tissue also revealed gross inflammatory changes in these groups. However histopathological examination of groups who were given therapeutic doses of simvastatin with and without Co Q10 for 90 days showed mild to moderate inflammatory changes but serum CK and LDH remained in the normal ranges in these groups. Conclusion: Our results suggest that Co Q10 supplementation could not produce any beneficial effects on the statin induced muscular adverse

A multienzyme complex channels substrates and electrons through acetyl-CoA and methane biosynthesis pathways in Methanosarcina.