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https://www.readbyqxmd.com/read/29922454/use-of-integrative-epigenetic-and-mrna-expression-analyses-to-identify-significantly-changed-genes-and-functional-pathways-in-osteoarthritic-cartilage
#1
A He, Y Ning, Y Wen, Y Cai, K Xu, Y Cai, J Han, L Liu, Y Du, X Liang, P Li, Q Fan, J Hao, X Wang, X Guo, T Ma, F Zhang
Aim: Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage. Patients and Methods: Genome-wide DNA methylation profiling of articular cartilage from five patients with OA of the knee and five healthy controls was conducted using the Illumina Infinium HumanMethylation450 BeadChip (Illumina, San Diego, California)...
May 2018: Bone & Joint Research
https://www.readbyqxmd.com/read/29887397/acute-o-2-sensing-role-of-coenzyme-qh-2-q-ratio-and-mitochondrial-ros-compartmentalization
#2
Ignacio Arias-Mayenco, Patricia González-Rodríguez, Hortensia Torres-Torrelo, Lin Gao, M Carmen Fernández-Agüera, Victoria Bonilla-Henao, Patricia Ortega-Sáenz, José López-Barneo
Acute O2 sensing by peripheral chemoreceptors is essential for mammalian homeostasis. Carotid body glomus cells contain O2 -sensitive ion channels, which trigger fast adaptive cardiorespiratory reflexes in response to hypoxia. O2 -sensitive cells have unique metabolic characteristics that favor the hypoxic generation of mitochondrial complex I (MCI) signaling molecules, NADH and reactive oxygen species (ROS), which modulate membrane ion channels. We show that responsiveness to hypoxia progressively disappears after inducible deletion of the Ndufs2 gene, which encodes the 49 kDa subunit forming the coenzyme Q binding site in MCI, even in the presence of MCII substrates and chemical NAD+ regeneration...
May 28, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29864244/effect-of-a-mitochondrial-targeted-coenzyme-q-analog-on-pancreatic-%C3%AE-cell-function-and-energetics-in-high-fat-fed-obese-mice
#3
Yumi Imai, Brian D Fink, Joseph A Promes, Chaitanya A Kulkarni, Robert J Kerns, William I Sivitz
We recently reported that mitoquinone (mitoQ, 500 μmol/L) added to drinking water of C57BL/6J mice attenuated weight gain and reduced oxidative stress when administered to high-fat (HF) fed mice. Here, we examined the effects of mitoQ administered to HF fed mice on pancreatic islet morphology, dynamics of insulin secretion, and islet mitochondrial metabolism. C57BL/6J mice were fed HF for 130 days while we administered vehicle (cyclodextrin [CD]) or mitoQ added to the drinking water at up to 500 μmol/L...
June 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29848676/combination-therapy-with-glucan-and-coenzyme-q-10-in-murine-experimental-autoimmune-disease-and-cancer
#4
Vaclav Vetvicka, Jana Vetvickova
BACKGROUND/AIM: Coenzyme Q10 is a well-accepted anti-oxidant agent known to play a protective role in various physiological and disease processes. Recently, Coenzyme Q10 is gaining attention as a substance with significant anti-inflammatory properties. β-Glucan is the most studied immunomodulator with significant synergetic effects with numerous bioactive molecules. We aimed to evaluate the possible synergistic effects of simultaneous use of coenzyme Q10 with the well-established immune modulator, β-glucan, on immune reactions and cancer development...
June 2018: Anticancer Research
https://www.readbyqxmd.com/read/29804512/suppression-of-respiratory-growth-defect-of-mutant-deficient-in-mitochondrial-phospholipase-a-1-by-overexpression-of-genes-involved-in-coenzyme-q-synthesis-in-saccharomyces-cerevisiae
#5
Shiho Morisada, Ikuhisa Nishida, Makoto Kawamukai, Hiroyuki Horiuchi, Ryouichi Fukuda
DDL1 encodes a mitochondrial phospholipase A1 involved in acyl chain remodeling of mitochondrial phospholipids and degradation of cardiolipin in Saccharomyces cerevisiae. The deletion of DDL1 leads to respiratory growth defects. To elucidate the physiological role of DDL1, we screened for genes that, when overexpressed, suppress the respiratory growth defect of the DDL1 deletion mutant. Introduction of COQ8, COQ9, or COQ5, which are involved in coenzyme Q (CoQ) synthesis, using a multicopy vector suppressed the respiratory growth defect of the DDL1 deletion mutant...
May 28, 2018: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/29781757/molecular-diagnosis-of-coenzyme-q-10-deficiency-an-update
#6
Delia Yubero, Raquel Montero, Carlos Santos-Ocaña, Leonardo Salviati, Placido Navas, Rafael Artuch
Coenzyme Q10 (CoQ) deficiency syndromes comprise a growing number of genetic disorders. While primary CoQ deficiency syndromes are rare diseases, secondary deficiencies have been related to both genetic and environmental conditions, which are the main causes of biochemical CoQ deficiency. The diagnosis is the essential first step for planning future treatment strategies, as the potential treatability of CoQ deficiency is the most critical issue for the patients. Areas covered: While the quickest and most effective tool to define a CoQ-deficient status is its biochemical determination in biological fluids or tissues, this quantification does not provide a definite diagnosis of a CoQ-deficient status nor insight about the genetic etiology of the disease...
June 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29766349/recent-developments-in-the-role-of-coenzyme-q10-for-coronary-heart-disease-a-systematic-review
#7
REVIEW
Jessica Ayers, Jamie Cook, Rachel A Koenig, Evan M Sisson, Dave L Dixon
PURPOSE OF REVIEW: This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease. RECENT FINDINGS: CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle...
May 16, 2018: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29743240/control-of-mitochondrial-superoxide-production-by-reverse-electron-transport-at-complex-i
#8
Ellen L Robb, Andrew R Hall, Tracy A Prime, Simon Eaton, Marten Szibor, Carlo Viscomi, Andrew M James, Michael P Murphy
The generation of mitochondrial superoxide (O2 •- ) by reverse electron transport (RET) at complex I causes oxidative damage in pathologies such as ischemia reperfusion injury, but also provides the precursor to H2 O2 production in physiological mitochondrial redox signaling. Here, we quantified the factors that determine mitochondrial O2 •- production by RET in isolated heart mitochondria. Measuring mitochondrial H2 O2 production at a range of Δp values and for several CoQ and NADH pool redox states obtained with the uncoupler p-trifluoromethoxyphenylhydrazone, we show that O2 •- production by RET responds to changes in O2 concentration, the magnitude of the proton-motive force (Δp), and the redox states of the coenzyme Q (CoQ) and NADH pools...
May 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29735117/pediatric-ataxia-focus-on-chronic-disorders
#9
David R Lynch, Ashley McCormick, Kimberly Schadt, Elizabeth Kichula
Evaluation of a pediatric patient presenting with ataxia can be expensive and time consuming. Acute causes tend to have a clear developmental paradigm, but chronic presentations are more likely to be secondary to a genetic disorder, either one that primarily causes ataxia or that presents ataxia as one of a multitude of symptoms. Evaluation should focus on a quick diagnosis for those that have treatment options and for those that require other systemic monitoring. Friedreich ataxia is the most common, and genetic testing can easily confirm the suspicion...
April 2018: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/29715001/modulation-of-catalytic-promiscuity-during-hydrogen-sulfide-oxidation
#10
Aaron P Landry, David P Ballou, Ruma Banerjee
The mitochondrial sulfide oxidation pathway prevents the toxic accumulation of hydrogen sulfide (H2 S), a signaling molecule that is maintained at low steady-state concentrations. Sulfide quinone oxidoreductase (SQR), an inner mitochondrial membrane-anchored protein, catalyzes the first and committing step in this pathway, oxidizing H2 S to persulfide. The catalytic cycle comprises sulfide addition to the active site cysteine disulfide in SQR followed by sulfur transfer to a small molecule acceptor, while a pair of electrons moves from sulfide, to FAD, to coenzyme Q...
June 15, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29694828/the-idebenone-metabolite-qs10-restores-electron-transfer-in-complex-i-and-coenzyme-q-defects
#11
REVIEW
Valentina Giorgio, Marco Schiavone, Chiara Galber, Marco Carini, Tatiana Da Ros, Valeria Petronilli, Francesco Argenton, Valerio Carelli, Manuel J Acosta Lopez, Leonardo Salviati, Maurizio Prato, Paolo Bernardi
Idebenone is a hydrophilic short-chain coenzyme (Co) Q analogue, which has been used as a potential bypass of defective complex I in both Leber Hereditary Optic Neuropathy and OPA1-dependent Dominant Optic Atrophy. Based on its potential antioxidant effects, it has also been tested in degenerative disorders such as Friedreich's ataxia, Huntington's and Alzheimer's diseases. Idebenone is rapidly modified but the biological effects of its metabolites have been characterized only partially. Here we have studied the effects of quinones generated during in vivo metabolism of idebenone with specific emphasis on 6-(9-carboxynonyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (QS10)...
April 22, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29684771/coenzyme-q-10-supplementation-reduces-oxidative-stress-and-decreases-antioxidant-enzyme-activity-in-children-with-autism-spectrum-disorders
#12
Elham Mousavinejad, Mohammad Ali Ghaffari, Forough Riahi, Maryam Hajmohammadi, Zeinab Tiznobeyk, Masoumeh Mousavinejad
Antioxidants and oxidative stress can participate in pathobiochemical mechanisms of autism spectrum disorders (ASDs). The aim was to identify the effects of early CoQ10 supplementation on oxidative stress in children with ASDs. Ninety children with ASDs were included in this study, based on DSM-IV criteria and using Childhood Autism Rating Scale (CARS) scores. Concentrations of CoQ10 , MDA, total antioxidant status (TAS) assay, and antioxidant enzymes (superoxide dismutase or SOD and glutathione peroxidase or GPx) activity were determined in serum before and after 100 days of supportive therapy with CoQ10 at daily doses of 30 and 60 mg...
July 2018: Psychiatry Research
https://www.readbyqxmd.com/read/29623830/the-effects-of-coenzyme-q10-supplementation-on-lipid-profiles-among-patients-with-metabolic-diseases-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#13
Nasrin Sharifi, Reza Tabrizi, Mahmood Moosazadeh, Naghmeh Mirhosseini, Kamran B Lankarani, Maryam Akbari, Maryam Chamani, Fariba Kolahdooz, Zatollah Asemi
BACKGROUND AND OBJECTIVE: Oxidative stress and inflammation are key parameters in developing metabolic disorders. Hence, antioxidant intake might be an appropriate approach. Several studies have evaluated the effect of coenzyme Q10 (CoQ10) supplementation on lipid profile among patients with metabolic diseases, though findings are controversial. The aim of this systematic review and meta-analysis was to determine the effects of CoQ10 supplementation on lipid profile in patients with metabolic disorders...
April 5, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29577824/cavitating-leukoencephalopathy-with-posterior-predominance-caused-by-a-deletion-in-the-apopt1-gene-in-an-indian-boy
#14
Suvasini Sharma, Preeti Singh, Erika Fernandez-Vizarra, Massimo Zeviani, Marjo S Van der Knaap, Ravindra Kumar Saran
A 5-year-old Indian boy presented with subacute onset regression of milestones associated with seizures and spasticity. The symptoms started after an attack of measles. The magnetic resonance imaging (MRI) of the brain showed cavitating leukodystrophy with posterior predominance. Molecular analysis of the APOPT1 gene, a recently described gene associated with mitochondrial leukodystrophy, showed the patient to be homozygous for a 12.82-kilobase deletion, including coding exon 3. Deletion of exon 3 produces a frameshift, predicting the translation of a truncated protein (p...
May 2018: Journal of Child Neurology
https://www.readbyqxmd.com/read/29574631/oxidative-stress-as-a-possible-mechanism-of-statin-induced-myopathy
#15
REVIEW
Yasin Ahmadi, Amir Ghorbanihaghjo, Mohsen Naghi-Zadeh, Neda Lotfi Yagin
Statins, inhibitors of hydroxy methyl glutaryl coenzyme-A (HMG-CoA) reductase, are the most widely used drugs for treating hypercholesterolemia. However, statins can cause disabling myopathy as their main adverse effect. Several molecular mechanisms underlie the statin-induced myopathy including the decrease in the levels of essential mevalonate and cholesterol derivatives. This review discusses a further mechanism involving the loss of other anti-oxidant defenses besides ubiquinone (Co-Q) in skeletal muscles which produce a significant amount of reactive oxygen species (ROS)...
June 2018: Inflammopharmacology
https://www.readbyqxmd.com/read/29560582/a-family-segregating-lethal-neonatal-coenzyme-q-10-deficiency-caused-by-mutations-in-coq9
#16
Amanda C Smith, Yoko Ito, Afsana Ahmed, Jeremy A Schwartzentruber, Chandree L Beaulieu, Erika Aberg, Jacek Majewski, Dennis E Bulman, Karina Horsting-Wethly, Diana Vermunt-de Koning, Richard J Rodenburg, Kym M Boycott, Lynette S Penney
Primary CoQ10 deficiency is a clinically and genetically heterogeneous, autosomal recessive disorder resulting from mutations in genes involved in the synthesis of coenzyme Q10 (CoQ10 ). To date, mutations in nine proteins required for the biosynthesis of CoQ10 cause CoQ10 deficiency with varying clinical presentations. In 2009 the first patient with mutations in COQ9 was reported in an infant with a neonatal-onset, primary CoQ10 deficiency with multi-system disease. Here we describe four siblings with a previously undiagnosed lethal disorder characterized by oligohydramnios and intrauterine growth restriction, variable cardiomyopathy, anemia, and renal anomalies...
March 20, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29530532/the-dilemma-of-diagnosing-coenzyme-q-10-deficiency-in-muscle
#17
Roan Louw, Izelle Smuts, Kimmey-Li Wilsenach, Lindi-Maryn Jonck, Maryke Schoonen, Francois H van der Westhuizen
BACKGROUND: Coenzyme Q10 (CoQ10 ) is an important component of the mitochondrial respiratory chain (RC) and is critical for energy production. Although the prevalence of CoQ10 deficiency is still unknown, the general consensus is that the condition is under-diagnosed. The aim of this study was to retrospectively investigate CoQ10 deficiency in frozen muscle specimens in a cohort of ethnically diverse patients who received muscle biopsies for the investigation of a possible RC deficiency (RCD)...
February 23, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29526616/n-acetylcysteine-and-vitamin-e-rescue-animal-longevity-and-cellular-oxidative-stress-in-pre-clinical-models-of-mitochondrial-complex-i-disease
#18
Erzsebet Polyak, Julian Ostrovsky, Min Peng, Stephen D Dingley, Mai Tsukikawa, Young Joon Kwon, Shana E McCormack, Michael Bennett, Rui Xiao, Christoph Seiler, Zhe Zhang, Marni J Falk
Oxidative stress is a known contributing factor in mitochondrial respiratory chain (RC) disease pathogenesis. Yet, no efficient means exists to objectively evaluate the comparative therapeutic efficacy or toxicity of different antioxidant compounds empirically used in human RC disease. We postulated that pre-clinical comparative analysis of diverse antioxidant drugs having suggested utility in primary RC disease using animal and cellular models of RC dysfunction may improve understanding of their integrated effects and physiologic mechanisms, and enable prioritization of lead antioxidant molecules to pursue in human clinical trials...
April 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29510674/evolutionary-analysis-of-mitochondrially-encoded-proteins-of-toad-headed-lizards-phrynocephalus-along-an-altitudinal-gradient
#19
Yuanting Jin, Yubin Wo, Haojie Tong, Sen Song, Lixun Zhang, Richard P Brown
BACKGROUND: Animals living at high altitude must adapt to environments with hypoxia and low temperatures, but relatively little is known about underlying genetic changes. Toad-headed lizards of the genus Phrynocephalus cover a broad altitudinal gradient of over 4000 m and are useful models for studies of such adaptive responses. In one of the first studies to have considered selection on mitochondrial protein-coding regions in an ectothermic group distributed over such a wide range of environments, we analysed nineteen complete mitochondrial genomes from all Chinese Phrynocephalus (including eight genomes sequenced for the first time)...
March 6, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29475487/highly-sensitive-and-selective-determination-of-redox-states-of-coenzymes-q-9-and-q-10-in-mice-tissues-application-of-orbitrap-mass-spectrometry
#20
Renu Pandey, Christopher L Riley, Edward M Mills, Stefano Tiziani
Coenzyme Q (CoQ) is a redox active molecule that plays a fundamental role in mitochondrial energy generation and functions as a potent endogenous antioxidant. Redox ratio of CoQ has been suggested as a good marker of mitochondrial dysfunction and oxidative stress. Nevertheless, simultaneous measurement of redox states of CoQ is challenging owing to its hydrophobicity and instability of the reduced form. In order to improve the analytical methodology, paying special attention to this instability, we developed a highly sensitive and selective high-resolution/accurate-mass (HR/AM) UHPLC-MS/MS method for the rapid determination of redox states of CoQ9 and CoQ10 by ultra-performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometry...
June 29, 2018: Analytica Chimica Acta
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