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Fig. l. Distribution of green fluorescence associated with Rh-l23 in liver hepatocytcs.- Control:-, + 50 u M adriamycin ; '" 50 u M adriamycin + 160 u M CoQIII:-...-, 50 fl-M adriamvcin + 320 u.M CoQltI. Measures after 2 hr incubation at 37°C in a Coulter EPICS-C cell sorter flow cytometer.
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The apparent Km for coenzyme Q10 in NADH oxidation by coenzyme Q (CoQ)-extracted beef heart mitochondria is close to their CoQ content, whereas both succinate and glycerol-3-phosphate oxidation (the latter measured in hamster brown adipose tissue mitochondria) are almost saturated at physiological CoQ concentration. Attempts to enhance NADH oxidati...
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COQ4 encodes a protein that organises the multienzyme complex for the synthesis of coenzyme Q(10) (CoQ(10)). A 3.9 Mb deletion of chromosome 9q34.13 was identified in a 3-year-old boy with mental retardation, encephalomyopathy and dysmorphic features. Because the deletion encompassed COQ4, the patient was screened for CoQ(10) deficiency.
A complete...
Citations
... Regarding the quality of the study sample, it is important to underline that in other literature studies [28,29] [19], in agreement with the idea that in muscle tissue the CoQ10 mitochondrial concentration seems not to possess saturation kinetics [33]. An increase in CoQ10 muscle concentration after exercise in CoQ10 phytosome-supplemented subjects [11] was previously observed, but no further studies had confirmed the data, up to the present study, that support and extend evidence for the first time in aging athletes. ...
... Early reports identified physiological concentrations of CoQ10 in mitochondria in the range of the Km of the respiratory complex I and II. This led to the conclusion that slight variations in CoQ10 content may produce significant effects on the efficiency of the mitochondrial respiratory chain [10]. Recent evidence supporting the existence of respiratory chain complexes in supermolecular assemblies, called supercomplexes or respirasomes, partially challenges this view in light of optimization of electron transfer processes in comparison to the random collision hypothesis; nonetheless, it is also believed that CoQ10 content is in a dynamic equilibrium between the free CoQ10 pool and the supercomplex-bound form. ...
Coenzyme Q10 (CoQ10) is an endogenous lipophilic quinone, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the aging process. In fact, coenzyme Q10 synthesis is known to decrease with age in different tissues including skin. Moreover, synthesis can be inhibited by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins, that are widely used hypocholesterolemic drugs. They target a key enzymatic step along the mevalonate pathway, involved in the synthesis of both cholesterol and isoprenylated compounds including CoQ10.
In the present study, we show that pharmacological CoQ10 deprivation at concentrations of statins > 10000 nM triggers intracellular oxidative stress, mitochondrial dysfunction and generates cell death in human dermal fibroblasts (HDF). On the contrary, at lower statin concentrations, cells and mainly mitochondria, are able to partially adapt and prevent oxidative imbalance and overt mitochondrial toxicity. Importantly, our data demonstrate that CoQ10 decrease promotes mitochondrial permeability transition and bioenergetic dysfunction leading to premature aging of human dermal fibroblasts in vitro.
... Electrons are carried out from complexes I and II to complex III by coenzyme Q (CoQ ). It has been demonstrated that lipoperoxidation is accompanied by reduced mitochondrial CoQ concentrations concomitantly with the decreased activities of respiratory chain enzymes, such as NADH-and succinate oxidases [22][23][24]. Increased levels of antioxidants have also been reported including CoQ in tissues as well as activities of antioxidant enzymes in experimental models of diseases associated with increased free radicals' generation such as diabetes mellitus [25][26][27]. The term "redox signaling" has been introduced to describe a regulatory process in which protective responses against oxidative damage are induced to reset the oxidant-antioxidant balance [28]. ...
... [14] It can protect lipids against free radicals. [15] Previous studies have demonstrated that CoQ10 production decreases in HD patients due to β-cells impairment, [14] hyperglycemia which in turn induces oxidative stress [16] and decreased conversion of ubiquinine to an active form (ubiquinol). [17] Also, circulating CoQ10 levels was significantly lower in HD patients than in those of controls. [18,19] Previous studies have demonstrated that CoQ10 supplementation can improve inflammation and oxidative stress in end-stage renal disease (ESRD) patients. ...
Background
The aim of the study was to determine the effects of coenzyme Q10 (CoQ10) supplementation on biomarkers of inflammation and oxidative stress among diabetic hemodialysis (HD) patients.
Methods
Sixty diabetic HD patients participated in the randomized, double blind, placebo-controlled clinical trial. They were randomly assigned into two groups to intake either 60 mg CoQ10 supplements (n = 30) or placebo (n = 30) twice a day for 12 weeks.
Results
After 12 weeks of intervention, CoQ10 supplementation significantly increased total antioxidant (TAC) (54.921 ± 26.437 vs. −126.781 ± 26.437, P < 0.001) and nitric oxide (NO) levels (4.121 ± 1.314 vs. −1.427 ± 1.314, P = 0.006) and decreased C-reactive protein (CRP) (−1.302 ± 0.583 vs. 0.345 ± 0.583, 0.042) levels compared with the placebo. We did not observe any significant effect of CoQ10 supplementation on malondialdehyde (MDA) and glutathione (GSH) levels compared with the placebo.
Conclusions
Overall, our study showed that CoQ10 supplementation to diabetic HD patients for 12 weeks was associated with increased levels of TAC and NO levels and decreased level of high-sensitivity CRP (hs-CRP) levels, but did not have any beneficial effects on MDA and GSH.
... Moreover, this ubiquinone may cause regeneration of reduced forms of vitamin E and C [4] and it shows stronger antioxidant properties than vitamin E [2]. In addition, CoQ10 can protect the lipids of membranes and blood circulation against peroxidation [7]. ...
... Research investment toward discovering appropriate supplements in complementary medicine has a high importance for optimal management of patient with diabetes [8]. Studies have shown that amongst the clinical supported supplements, Q10 supplements are one of the most popular ones that might be valuable in the management of neurodegenerative and cardiovascular diseases [5,7,[9][10][11]. ...
Low grade inflammation and oxidative stress are the key factors in the pathogenesis and development of diabetes and its complications. Coenzyme Q10 (CoQ10) is known as an antioxidant and has a vital role in generation of cellular energy providing. This study was undertaken to evaluate the effects of CoQ10 supplementation on lipid profiles and glycemic controls in patients with diabetes.
Fifty patients with diabetes were randomly allocated into two groups to receive either 150 mg CoQ10 or placebo daily for 12 weeks. Before and after supplementation, fasting venous blood samples were collected and lipid profiles containing triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) and glycemic indices comprising of fasting plasma glucose (FPG), insulin and hemoglobin A1C (HbA1C) were measured. Insulin resistance was calculated using HOMA-IR index.
Forty patients completed the study. After intervention FPG and HbA1C were significantly lower in the CoQ10 group compared to the placebo group, but there were no significant differences in serum insulin and HOMA-IR between the two groups. Although total cholesterol did not change in the Q10 group after supplementation, triglyceride and HDL-C significantly decreased and LDL-C significantly increased in the CoQ10 group.
The present study showed that treatment with Q10 may improve glycemic control with no favorable effects on lipid profiles in type 2 patients with diabetes.
Trial registration
IRCT registry number: IRCT138806102394N1
... We have previously shown that shutdown of the SQSTM1/p62 gene can result in decreases in mitochondrial energy production [70], as well as increased oxidative damage to mitochondrial DNA [15,16]. Other key modulators of mitochondrial function include regulation of intracellular Ca +2 levels by Bcl-2 [59] and abrogation of electron transfer along the respiration chain by coenzyme Q10 (CoQ10) deficiency [51]. Overexpression of either of these proteins results in improved mitochondrial function [59,68], an observation we have also seen with p62 overexpression in mouse embryonic fibroblasts [70]. ...
... The Coenzyme Qn (CoQn) family, also known as the ubiquinones (Fig. 1), have a number of important biofunctions that include acting as mobile mediators for electron transfer and protein translocation between redox enzymes in the electron transport chain of mitochondria and bacterial respiratory systems. [1][2][3] Coenzyme Q (CoQ) is also known to act as an antioxidant by reducing free radicals that can cause damage to structural lipids or proteins in the membrane, not only in mitochondria but in any cellular CoQ containing membranes. 3 In addition, CoQ is a valuable medicine, especially CoQ 10 , which have a beneficial effect on various heart-related diseases. ...
The title compound, a key intermediate for preparing Coenzyme Qn family, was prepared in high yield by a reaction sequence starting from the commercially available 3, 4, 5-trimethoxy-benzadehyde via Wolff–Kishner reduction, Vilsmeier–Haack reaction, Blanc chloromethylation reaction, Dakin reaction and oxidation.
... It has been found in virtually all cells of the human body, including the heart, liver and skeletal muscles [2]. Initially, it became a popular supplement due to participation in two major physiological activities: as a mitochondrial electron-transporter in the high-energy metabolic pathways of liver cells and other cells of the body and as an antioxidant against free radicals and lipid peroxidation [3][4][5]. Recently, CoQ10, as a cutaneous antioxidant and energiser, had been demonstrated to prevent photoaging in topical application. It not only penetrates into the viable epidermis and reduces the level of oxidation and wrinkle depth but also reduces the detrimental effects of ultraviolet A (UVA) on dermal fibroblasts, which maintain the dermal matrix. ...
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.
... We observed a biphasic increase in ATP synthesis with increasing amounts of CoQ 10 , which may reflect the incorporation of CoQ 10 into mitochondrial membranes [40]. It has been reported that the CoQ 10 concentration in the mitochondrial membrane is not physiologically saturating for maximal electron transfer [41,42] and that addition of exogenous CoQ 10 enhances the respiratory turnover rate above physiological levels [43]. We also observed a marked increase in non-mitochondrial ATP synthesis with CoQ 10 , in excess of that induced by phospholipid alone, which suggests additional functions for CoQ 10 as a component of extra-mitochondrial redox reactions [44]. ...
Marked progress has been made over the past 15 years in defining the specific biochemical defects and underlying molecular mechanisms of oxidative phosphorylation disorders, but limited information is currently available on the development and evaluation of effective treatment approaches. Metabolic therapies that have been reported to produce a positive effect include coenzyme Q(10) (ubiquinone), other antioxidants such as ascorbic acid and vitamin E, riboflavin, thiamine, niacin, vitamin K (phylloquinone and menadione), and carnitine. The goal of these therapies is to increase mitochondrial ATP production, and to slow or arrest the progression of clinical symptoms. In the present study, we demonstrate for the first time that there is a significant increase in ATP synthetic capacity in lymphocytes from patients undergoing cofactor treatment. We also examined in vitro cofactor supplementation in control lymphocytes in order to determine the effect of the individual components of the cofactor treatment on ATP synthesis. A dose-dependent increase in ATP synthesis with CoQ(10) incubation was demonstrated, which supports the proposal that CoQ(10) may have a beneficial effect in the treatment of oxidative phosphorylation (OXPHOS) disorders.
... 5 Within the cell, CoQ 10 is found in highest concentrations within the inner mitochondrial membrane, the area with the highest rate of free radical production. 6 The content of CoQ 10 in tissues peaks in the early twenties and then gradually decreases with age. 7 Coenzyme Q 10 has two key functions, first, as an integral component of the electron transfer chain that carries electrons from complex I and II to complex III to generate ATP and second, as a lipid-soluble anti-oxidant. ...
... 7 Coenzyme Q 10 has two key functions, first, as an integral component of the electron transfer chain that carries electrons from complex I and II to complex III to generate ATP and second, as a lipid-soluble anti-oxidant. 6 Many studies of the therapeutic efficacy of CoQ 10 have been confounded by the variable bioavailability of the various CoQ 10 preparations used. High serum levels early after administration are important in situations where there is limited time for CoQ 10 to be given, such as prior to cardiac surgery. ...
Studies of the therapeutic efficacy of coenzyme Q10 (CoQ10) have been confounded by the variable bioavailability of numerous CoQ10 preparations. The aims of the present study were to determine the early serum levels attained by two different preparations of CoQ10, a soybean oil-based preparation and a complex micelle emulsion and to assess whether these preparations of oral CoQ10 influence plasma lipid profiles. Twelve healthy individuals received 300 mg CoQ10 daily of either preparation for 7 days in a double-blind cross-over design with a 21-day washout period. Blood samples to determine serum levels of CoQ10 and lipids were taken at baseline, after 24 h and 7 days. Both preparations induced significant increases in serum CoQ10 levels at 24 h and 7 days. These were for soy oil: baseline 0.27 ± 0.03 mol/L, 24 h 0.50 ± 0.04 mol/L (180%) and 7 days 0.80 ± 0.05 mol/L (291%), mean ± SEM; for emulsion: baseline 0.29 ± 0.03 mol/L, 24 h 0.45 ± 0.03 mol/L (150%) and 7 days 0.79 ± 0.06 mol/L (270%). There were no significant differences between CoQ10 levels for the two preparations at either time point. There was no change in any of the serum lipids following the 7 days treatment. We conclude that administration of either a soy oil suspension or a complex emulsion of CoQ10 increases serum levels to the therapeutic range within 1 week.
