Effect of coenzyme Q10 supplementation on post-vitrification mouse embryo development

Objective:To investigate the effects of coenzyme Q10(CoQ10)supplementation on post-vitrification embryo development and gross morphology.Methods:Balb/c mouse embryos were cultured in potassium simplex optimised medium(KSOM)with varying CoQ10 concentrations[0(control),20,40,and 60μM].The most effective CoQ10 concentration(40μM)was selected for subsequent post-vitrification morphology study.Embryos were randomly divided into four groups:Group A(non-vitrified without CoQ10),Group B(non-vitrified with CoQ10),Group C(vitrified without CoQ10),and Group D(vitrified with CoQ10),followed by vitrification at the 8-cell stage.Survival rates and development until the blastocyst stage were evaluated through morphological examinations using ASEBIR's system,distinguishing normal and abnormal embryos.Results:Supplementation of 40μM CoQ10 significantly increased blastocyst formation(95%)compared to the control group(92%),20μM(62%),and 60μM(56%)(P<0.001).Following vitrification,Group D exhibited a significant increase in blastocyst formation(92%)compared to Group C(82%)(P<0.05).Morphological assessments indicated superior embryo quality in Group B over Group D during the cleavage stage,morula,and blastocyst(P<0.05).Conclusions:CoQ10 supplementation exhibits promising potential to enhance preimplantation embryo development,increase blastocyst formation rates,and improve embryo quality post-vitrification.This offers a promising approach to mitigate oxidative stress on embryos,potentially improving overall assisted reproductive technology outcomes.

Effects of dietary coenzyme Q10 supplementation during gestation on the embryonic survival and reproductive performance of high‑parity sows

Background Fertility declines in high-parity sows.This study investigated whether parity-dependent declines in embryonic survival and reproductive performance could be restored by dietary coenzyme Q10(CoQ10)supplementation.Methods Two experiments were performed.In Exp.1,30 young sows that had completed their 2nd parity and 30 high-parity sows that had completed their 10^(th)parity,were fed either a control diet(CON)or a CON diet supple-mented with 1 g/kg CoQ10(+CoQ10)from mating until slaughter at day 28 of gestation.In Exp.2,a total of 314 post-weaning sows with two to nine parities were fed the CON or+CoQ10 diets from mating throughout gestation.Results In Exp.1,both young and high-parity sows had a similar number of corpora lutea,but high-parity sows had lower plasma CoQ10 concentrations,down-regulated genes involved with de novo CoQ10 synthesis in the endome-trium tissues,and greater levels of oxidative stress markers in plasma and endometrium tissues.High-parity sows had fewer total embryos and alive embryos,lower embryonic survival,and greater embryo mortality than young sows.Dietary CoQ10 supplementation increased the number of live embryos and the embryonic survival rate to levels simi-lar to those of young sows,as well as lowering the levels of oxidative stress markers.In Exp.2,sows showed a parity-dependent decline in plasma CoQ10 levels,and sows with more than four parities showed a progressive decline in the number of total births,live births,and piglets born effective.Dietary supplementation with CoQ10 increased the number of total births,live births,and born effective,and decreased the intra-litter covariation coefficients and the percentage of sows requiring farrowing assistance during parturition.Conclusions Dietary CoQ10 supplementation can improve the embryonic survival and reproductive performance of gestating sows with high parity,probably by improving the development of uterine function.

Advances in the Coenzyme Q10 Biosynthesis Pathway in Rhodobacter sphaeroides and the Enhancement of Coenzyme Q10 Production Based on Metabolic Engineering

Coenzyme Q10 is widely used in food,cosmetics and pharmaceuticals,possessing a broad market.Rhodobacter sphaeroides is enriched in natural coenzyme Q10 and is becoming an important microorganism for producing natural coenzyme Q10.The paper reviewed the biosynthesis pathways of coenzyme Q10 in R.sphaeroides and the advances in enhancement of coenzyme Q10 production in R.sphaeroides based on metabolic engineering.

Photocatalytic oxidation of primary and secondary benzyl alcohol catalyzed by two coenzyme NAD^+ models

Photocatalytic oxidation of primary and secondary benzyl alcohol to corresponding benzaldehyde or acetophenone using Acr＋Cl04- or PhAcr＋Cl04- as photocatalysts under visible light irradiation at room temperature.

Evidence on neuroprotective properties of coenzyme Q10 in the treatment of glaucoma

Glaucoma, the leading cause of visual impairment and irreversible blindness worldwide, is a multifactorial, progressive optic neuropathy characterized by loss of retinal ganglion cells, alterations of the optic nerve head, and specific visual field defects. Clinical evidence shows that intraocular pressure is the major risk factor of the treatable disease. However, in some patients, glaucoma develops and continues to progress despite normal intraocular pressure values, suggesting that other risk factors are involved in the disease. Consequently, neuroprotective treatments, focused on preventing retinal ganglion cells death by acting on different therapeutic strategies but not focused on intraocular pressure reduction, has therefore become of great interest. In this contest, coenzyme Q10, showing evidence in slowing or reversing pathological changes typical of the disease, has been proposed as a potential neuroprotective agent in glaucoma. In this review, we describe the possible mechanisms of action of coenzyme Q10 and the recent evidence in literature regarding the neuroprotective activity of the molecule.

Effect of Tumor Necrosis Factor-α on Acyl Coenzyme A: Cholesteryl Acyltransferase Activity and ACAT1 Gene Expression in THP-1 Macrophages

In order to explore the effect and mechanisms of tumor necrosis factor-α （TNF-α） on the activity of the acyl coenzyme A： cholesteryl acyltransferase （ACAT）, THP-I monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α （60 ng/mL） was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α （60 ng/mL）. The results indicated that ACAT activity in THP-I macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-I macrophages after treatment with TNF-α （P〈0.05）. It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.

Breeding of Coenzyme Q_(10) Produced Strain by Low-Energy Ion Implantation and Optimization of Coenzyme Q_(10) Fermentation

In order to increase the production efficiency of coenzyme Q10, the original strain Agrobacterium tumefaciens ATCC 4452 was mutated by means of Nitrogen ions implantation. A mutant strain, ATX 12, with high contents of coenzyme Q10 was selected. Subsequently, the conditions such as carbohydrate concentration, nitrogen source concentration, inoculum＇s size, seed age, aeration and temperature which might affect the production of CoQ10 were investigated in detail. Under optimal conditions, the maximum concentration of the intracellular CoQ10 reached 200.3 mg/L after 80 h fed-batch fermentation, about 245% increasing in CoQ10 production after ion implantation, compared to the original strain.

Validation and application of Vierordt’’s spectrophotometric method for simultaneous estimation of tamoxifen/coenzyme Q10 in their binary mixture and pharmaceutical dosage forms

For the sake of improving patient compliance and sustainability of chemotherapy healthcare system, both TC and CoQ10 were formulated as solid lipid nanoparticles (SLNs). The study was focused on establishing and validating a simple and reproducible spectrophotometric method for simultaneous determination of TC and CoQ10 in their binary mixture or pharmaceutical dosage forms. A new method based on simultaneous estimation of drug mixture without prior separation was developed. Validation parameters were checked with International Conference on Harmonization (ICH) guidelines. The accuracy and reproducibility of proposed method was statistically compared to HPLC. The TC and CoQ10 were quantified at absorptivity wavelengths of 236 nm and 275 nm, respectively. Calibration curves obeyed Beer’s law in range of 2–14 μg/ml with a correlation coefficient (R^2) of 0.999 in both methanol and simplified simulated intestinal fluid (SSIF). The %means recovery of TC and Co Q10 in pure state or binary mixture at various concentration levels were all around 100%.The low values of SD and %RSD (<2%) confirm high precision and accuracy of the proposed method. Formulated SLNs showed different %means recovery in range 81–92% for TC and 32–59% for CoQ10. The data obtained by applying simultaneous Vierordt’s equations showed no statistical significance in comparison to HPLC. Vierordt’s method was successfully applied as a simple, accurate, precise, and economical analysis method for estimating TC and CoQ10 concentrations in pure state, binary mixture and pharmaceutical dosage forms.

Coenzyme Q10 as a therapeutic candidate for treating inherited photoreceptor degeneration

Inherited photoreceptor degeneration（IPD）：The human retina is a highly specialised tissue that enables the perception of light across a range of intensities and colours.It covers about65%of the inner surface of the eye and contains three layers of cells：the outer nuclear layer（ONL）containing the cell bodies and nuclei of the light-sensitive rod and cone photoreceptorswhose photopigment-containing outer segments form the photoreceptor layer; the inner nuclear layer （INL） containing bipolar, horizontal and amacrine cells; and the ganglion cell layer （GCL） from which the optic nerve arises. There are two layers of synaptic connections between these three layers： the photoreceptors synapse with second order neurons, mainly bi- polar cells, in the outer plexiform layer （OPL）, while in turn the bipolar cells form connections in the inner plexiform layer （IPL） with ganglion cells. The retinal pigment epithelium （RPE） lies directly behind the photoreceptor layer, is heavily pigmented to reduce scattering of light, and is essential for the nourishment, maintenance and metabolism of photoreceptors.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy

AIMTo determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration.

High-level expression of 4-coumarate:coenzyme A ligase gene Pt4CL1 of Populus tomentosa in E. coli

In order to investigate the enzymatic properties of the 4CL1 of Populus tomentosa, the recombinant expression vector pQE31-4CL 1 was constructed. The recombinant was identified by three restriction endonucleases, then the vector pQE31-4CL 1 was transformed into expression host M15 （pREP4） and induced by isopropyl-a-D-thiogalactoside （IPTG） to express 60 kD fused protein Pt4CL1. The biologically active Pt4CL1, expressed as soluble protein, was achieved with 0.6 mmol＇L-1 IPTG induction as the expression temperature declined from 37 to 28℃. The 6-His tag facilitates affinity binding to Ni^2＋-nitrolotriacetic acid （NTA） and enables one-step purification to acquire the molecular SDS-PAGE electrophoresis purity of the active 4CL1 protein by agarose coupled with Ni^2＋-NTA affinity chromatography. The optimal substrate for Pt4CL 1 was 4-coumarate.

Coenzyme Q10 in neurodegenerative disorders: Potential benefit of Co Q10 supplementation for multiple system atrophy

Coenzyme Q10(Co Q10) is an essential cofactor in the mitochondrial respiratory pathway and also functions as a lipid-soluble antioxidant. Co Q10 deficiency has been implicated in many clinical disorders and aging. Primary Co Q10 deficiency is a group of recessively inherited diseases caused by mutations in any gene involved in the Co Q10 biosynthesis pathway. Although primary Co Q10 deficiency is rare, its diagnosis is important because it is potentially treatable with exogenous Co Q10. Multiple system atrophy(MSA) was recently shown to be linked to mutations in the COQ2 gene, one of the genes involved in the Co Q10 biosynthesis pathway. MSA is relatively common in adult-onset neurodegenerative diseases characterized by Parkinsonism, cerebellar ataxia and autonomic failures. Because COQ2 mutations are associated with an increased risk of MSA, oral Co Q10 supplementation may be beneficial for MSA, as for other primary Co Q10 deficiencies. Statins are 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that inhibit the biosynthesis of cholesterol, as well as the synthesis of mevalonate, a critical intermediate in cholesterol synthesis. Statin therapy has been associ-ated with a variety of muscle complaints from myalgia to rhabdomyolysis. Statin treatment carries a potential risk of Co Q10 deficiency, although no definite evidence has implicated CQ10 deficiency as the cause of statinrelated myopathy.

Kinetic Studies of a Coenzyme B12 Dependent Reaction Catalyzed by Glutamate Mutase from <i>Clostridium cochlearium</i>

The coenzyme B12 dependent glutamate mutase is composed of two apoenzyme proteins subunits;S and E2, which while either fused or separate assemble with coenzyme B12 to form an active holoenzyme (E2S2-B12) for catalyzing the reversible isomerization between (S)-glutamate and (2S, 3S)-3-methylas- partate. In order to assay the activity of glutamate mutase by UV spectrophotometry, this reaction is often coupled with methylaspartase which deaminates (2S, 3S)-3-methylaspartate to form mesaconate (λmax = 240 nm, Ɛ240 = 3.8 mM-1·cm-1). The activities of different reconstitutions of glutamate mutase from separate apoenzyme components S and E in varied amounts of coenzyme B12 and adenosylpeptide B12 as cofactors were measured by this assay and used to reveal the binding properties of the cofactor by the Michaelis- Menten Method. The values of Km for coenzyme B12 in due to reconstitutions of holoenzyme in 2, 7 and 14 S: E were determined as;1.12 ± 0.04 μM, 0.7 ± 0.05 μM and 0.52 ± 0.06 μM, respectively, so as those of adenosylpeptide B12;1.07 ± 0.04 μM and 0.35 ± 0.05 μM as obtained from respective 2 and 14 S: E compositions of holoenzyme. Analysis of these kinetics results curiously associates the increasing affinity of cofactors to apoenzyme with increased amount of component S used in reconstituting holoenzyme from separate apoenzyme components and cofactor. Moreover, in these studies a new method for assaying the activity of glutamate mutase was developed, whereby glutamate mutase activity is measured via depletion of NADH (λmax = 340 nm, Ɛ340 = 6.3 mM-1·cm-1) as determined by UV spectrophotometry after addition of (2S, 3S)-3-methylaspartate and pyruvate to a mixture of E2S2-B12 and two auxiliary holoenzymes system;pyridoxal-5-phosphate dependent glutamate-pyruvate aminotransferase and NADH dependent (R)-2-hydroxyglutarate dehydrogenase. The activity of glutamate-pyruvate aminotransferase was relatively complete recovered upon the addition of (S)-glutamate and pyruvate to the mixtures of hologlutamate-pyruvate aminotransferase and (R)-2-hydroxylglutarate dehydrogenase which were incubated with each putative inhibitor of glutamate mutase. Additionally, the new assay was used to determine the kinetic constants of (2S, 3S)-3-methylaspartate in the reaction of glutamate mutase as Km= 7 ± 0.07 mM and kcat= 0.54 ± 0.6 s-1. Application of Briggs-Haldane formula allowed the calculation of an equilibrium constant of the reversible isomerization, Keq = [(S)-glutamate] × [(2S, 3S)-3-methylaspartate]-1 = 16, where the kinetic constants of (S)-glutamate were determined by the standard methylaspartase coupled assay.

Effect of levocarnitine+coenzyme Q10 adjuvant therapy on vasoactive molecules,endothelial injury and oxidative stress in patients with chronic heart failure

Objective: To study the effect of levocarnitine + coenzyme Q10 adjuvant therapy on vasoactive molecules, endothelial injury and oxidative stress in patients with chronic heart failure. Methods: A total of 90 patients with chronic heart failure who were treated in the hospital between December 2014 and December 2016 were collected and divided into control group and observation group by random number table method, 45 cases in each group. Control group received conventional therapy, and observation group received levocarnitine + coenzyme Q10 adjuvant therapy on the basis of conventional therapy. The differences in vasoactive molecule, endothelial injury and oxidative stress levels were compared between the two groups before and after treatment. Results: Before treatment, the differences in vasoactive molecule, endothelial injury and oxidative stress levels were not statistically significant between the two groups of patients. After treatment, serum vasoactive molecules ET-1, AngⅡ and TXB2 contents of observation group were lower than those of control group while NO content was higher than that of control group;endothelial function indexes FMD level was higher than that of control group;serum oxidative stress indexes SOD and T-AOC contents were higher than those of control group while MDA and ROS contents were lower than those of control group. Conclusion: Levocarnitine + coenzyme Q10 adjuvant therapy can optimize the vascular activity, and reduce the endothelial injury and systemic oxidative stress response in patients with chronic heart failure.

Higher levels of the lipophilic antioxidants coenzyme Q_(10) and vitamin E in long-lived termite queens than in short-lived workers

Termite queens and kings live longer than nonreproductive workers.Several molecular mechanisms contributing to their long lifespan have been investigated;however,the underlying biochemical explanation remains unclear.Coenzyme Q(CoQ),a component of the mitochondrial electron transport chain,plays an essential role in the lipophilic antioxidant defense system.Its beneficial effects on health and longevity have been well studied in several organisms.Herein,we demonstrated that long-lived termite queens have significantly higher levels of the lipophilic antioxidant CoQ_(10) than workers.Liquid chromatography analysis revealed that the levels of the reduced form of CoQ_(10) were 4 fold higher in the queen's body than in the worker's body.In addition,queens showed 7 fold higher levels of vitamin E,which plays a role in antilipid peroxidation along with CoQ,than workers.Furthermore,the oral administration of CoQ_(10) to termites increased the CoQ_(10) redox state in the body and their survival rate under oxidative stress.These findings suggest that CoQ_(10) acts as an efficient lipophilic antioxidant along with vitamin E in long-lived termite queens.This study provides essential biochemical and evolutionary insights into the relationship between CoQ_(10) concentrations and termite lifespan extension.

Corrigendum to“Delivery of coenzyme Q10 loaded micelle targets mitochondrial ROS and enhances efficiency of mesenchymal stem cell therapy in intervertebral disc degeneration”[Bioact.Mater.23(2023)247-260]

This corrects the article“Delivery of coenzyme Q10 loaded micelle targets mitochondrial ROS and enhances efficiency of mesenchymal stem cell therapy in intervertebral disc degeneration”in volume 23 on page 247.The authors regret that the printed version of the above article contains some errors which are not identified during the proofing stage.

Delivery of coenzyme Q10 loaded micelle targets mitochondrial ROS and enhances efficiency of mesenchymal stem cell therapy in intervertebral disc degeneration

Stem cell transplantation has been proved a promising therapeutic instrument in intervertebral disc degeneration(IVDD).However,the elevation of oxidative stress in the degenerated region impairs the efficiency of mesenchymal stem cells(BMSCs)transplantation treatment via exaggeration of mitochondrial ROS and promotion of BMSCs apoptosis.Herein,we applied an emulsion-confined assembly method to encapsulate Coenzyme Q10(Co-Q10),a promising hydrophobic antioxidant which targets mitochondria ROS,into the lecithin micelles,which renders the insoluble Co-Q10 dispersible in water as stable colloids.These micelles are injectable,which displayed efficient ability to facilitate Co-Q10 to get into BMSCs in vitro,and exhibited prolonged release of Co-Q10 in intervertebral disc tissue of animal models.Compared to mere use of Co-Q10,the Co-Q10 loaded micelle possessed better bioactivities,which elevated the viability,restored mitochondrial structure as well as function,and enhanced production of ECM components in rat BMSCs.Moreover,it is demonstrated that the injection of this micelle with BMSCs retained disc height and alleviated IVDD in a rat needle puncture model.Therefore,these Co-Q10 loaded micelles play a protective role in cell survival and differentiation through antagonizing mitochondrial ROS,and might be a potential therapeutic agent for IVDD.

Protein engineering of oxidoreductases utilizing nicotinamide-based coenzymes,with applications in synthetic biology

Two natural nicotinamide-based coenzymes(NAD and NADP)are indispensably required by the vast majority of oxidoreductases for catabolism and anabolism,respectively.Most NAD(P)-dependent oxidoreductases prefer one coenzyme as an electron acceptor or donor to the other depending on their different metabolic roles.This coenzyme preference associated with coenzyme imbalance presents some challenges for the construction of high-efficiency in vivo and in vitro synthetic biology pathways.Changing the coenzyme preference of NAD(P)-dependent oxidoreductases is an important area of protein engineering,which is closely related to product-oriented synthetic biology projects.This review focuses on the methodology of nicotinamide-based coenzyme engineering,with its application in improving product yields and decreasing production costs.Biomimetic nicotinamide-containing coenzymes have been proposed to replace natural coenzymes because they are more stable and less costly than natural coenzymes.Recent advances in the switching of coenzyme preference from natural to biomimetic coenzymes are also covered in this review.Engineering coenzyme preferences from natural to biomimetic coenzymes has become an important direction for coenzyme engineering,especially for in vitro synthetic pathways and in vivo bioorthogonal redox pathways.

Two Divergent Members of 4-Coumarate： Coenzyme A Ligase from Salvia miltiorrhiza Bunge： cDNA Cloning and Functional Study

4-Coumarate ： coenzyme A Ilgase （4CL） Is one of the key enzymes In phenylpropanoid metabolism leading to series of phenollcs, Including water-soluble phenolic acids, which are important compounds determining the medicinal quality of Danshen （Salvia miltiorrhiza Bunge）, a traditional Chinese medicinal herb. To Investigate the function of 4CL in the biosynthesis of water-soluble phenolic acid in Danshen, we have cloned two cDNAs （Sm4CL1 and Sm4CL2） encoding divergent 4CL members by applying nested reverse transcrlptlon-polymerase chain reaction （RT-PCR） with degenerate primers followed by 5′/3′rapid amplification of cDNA ends （RACE） （Note, these sequence data have been submitted to the GenBank database under accession numbers AY237163 and AY237164）. Either of the coding regions was inserted into a pRSET vector and a kinetic assay was performed with purified recombinant proteins. The substrate utilization profile of Sm4CL1 was distinct from that of Sm4CL2. The Km values of Sm4CL1 and Sm4CL2 to 4-coumarlc acid were （72.20±4.10） and （6.50±1.45） μmol/L, respectively. These results, In conjunction with Northern blotting and other information, imply that Sm4CL2 may play an Important role in the biosynthesis of watersoluble phenolic compounds, whereas Sm4CL1 may play a minor role in the pathway. Southern blotting analysis suggested that both Sm4CL1 and Sm4CL2 genes are present as a single copy and are located at different sites In the genome.

Drosophila sbo regulates lifespan through its function in the synthesis of coenzyme Q in vivo

CoQ is an essential electron cartier in the mitochondrial respiratory chain of both eukaryotes and prokaryotes. It consists of a benzoquinone head group and a hydrophobic polyisoprenoid tail. The genes （COQ1-9） involved in CoQ biosynthesis have been characterized in yeast. In this study, we generated and molecularly characterized a mutant allele of a novel Drosophila gene, sbo, which encodes a protein that is predicted to catalyze the prenylation of p-hydroxybenzoate with the isoprenoid chain during the process of CoQ synthesis. Expression of sbo in yeast rescues the lethality of ACOQ2 mutant cells, indicating that sbo is a functional homolog of COQ2. HPLC results show that the levels of CoQ9 and COQlo were significantly reduced in sbo heterozygous adult flies. Furthermore, the mean lifespans of males and females heterozygous for sbo are extended by 12.5% and 30.8%, respectively. Homozygous sbo animals exhibit reduced activities of the insulin/insulin-like growth factor signaling （IIS） pathway. Taken together, we conclude that sbo is an essential gene for Drosophila development, mutation of which leads to an extension of lifespan most likely by altering endogenous CoQ biosynthesis.