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https://www.readbyqxmd.com/read/28921079/identification-of-a-new-isoindole-2-yl-scaffold-as-a-qo-and-qi-dual-inhibitor-of-cytochrome-bc-1-complex-virtual-screening-synthesis-and-biochemical-assay
#1
Homa Azizian, Kowsar Bagherzadeh, Sophia Shahbazi, Niusha Sharifi, Massoud Amanlou
Respiratory chain ubiquinol-cytochrome (cyt) c oxidoreductase (cyt bc 1 or complex III) has been demonstrated as a promising target for numerous antibiotics and fungicide applications. In this study, a virtual screening of NCI diversity database was carried out in order to find novel Qo/Qi cyt bc 1 complex inhibitors. Structure-based virtual screening and molecular docking methodology were employed to further screen compounds with inhibition activity against cyt bc 1 complex after extensive reliability validation protocol with cross-docking method and identification of the best score functions...
September 18, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28883650/a-novel-and-stress-adaptive-alternative-oxidase-derived-from-alternative-splicing-of-duplicated-exon-in-oyster-crassostrea-virginica
#2
Ming Liu, Ximing Guo
Alternative oxidase (AOX) is a mitochondrial inner-membrane oxidase that accepts electrons directly from ubiquinol and reduces oxygen to water without involving cytochrome-linked electron transport chain. It is highly conserved in many non-vertebrate taxa and may protect cells against hypoxia and oxidative stress. We identified two AOX mRNAs in eastern oyster Crassostrea virginica, CvAOXA and CvAOXB, which differ by 170 bp but encode AOXs of the same size. Sequence analyses indicate that CvAOX has 10 exons with a tandem duplication of exon 10, and 3' alternative splicing using either the first or second exon 10 produces the two variants CvAOXB or CvAOXA, respectively...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28755974/a-pilot-study-exploring-the-effects-of-ubiquinol-on-brain-genomics-after-traumatic-brain-injury
#3
Janet D Pierce, Qiuhua Shen, Jill Peltzer, Amanda Thimmesch, John B Hiebert
BACKGROUND: Traumatic brain injury is a major cause of morbidity and mortality that affects military service members and veterans. PURPOSE: Explore the effects of ubiquinol before traumatic brain injury on cerebral gene expression to elucidate molecular mechanisms of ubiquinol neuroprotection. METHOD: In this experimental study, Fisher rats in the untreated (n = 2) and ubiquinol-treated (n = 2) groups received respectively either normal saline or ubiquinol 30 min before traumatic brain injury induced by controlled cortical impact...
July 1, 2017: Nursing Outlook
https://www.readbyqxmd.com/read/28750029/ubiquinol-cytochrome-c-reductase-core-protein-1-may-be-involved-in-delayed-cardioprotection-from-preconditioning-induced-by-diazoxide
#4
Zonghong Long, Guangyou Duan, Hong Li, Tingting Yi, Xiaoxiao Wu, Feng Chen, Zhuoxi Wu, Yuqi Gao
This study aimed to use long-term diazoxide treatment to establish a loss-of-cardioprotection model and then perform proteomics analysis to explore which proteins of mitochondrial inner membrane (MIM) are potentially involved in delayed cardioprotection. Rats received 1 to 8 weeks of diazoxide treatments (20 mg•kg-1•d-1) to establish a loss-of-cardioprotection model in different groups. Detection of serum cTnI levels and cell apoptosis assays in heart tissue were performed. Then, rats MIM after 0, 4 and 6 weeks of diazoxide treatment was isolated and proteomics analysis was performed...
2017: PloS One
https://www.readbyqxmd.com/read/28714002/identification-of-key-genes-in-gram%C3%A2-positive-and-gram%C3%A2-negative-sepsis-using-stochastic-perturbation
#5
Zhenliang Li, Ying Zhang, Yaling Liu, Yanchun Liu, Youyi Li
Sepsis is an inflammatory response to pathogens (such as Gram‑positive and Gram‑negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram‑positive and Gram‑negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram‑positive samples and 25 Gram‑negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram‑negative and Gram‑negative samples using cluster software and the TreeView software...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28702034/cardr1-an-rna-dependent-rna-polymerase-plays-a-positive-role-in-pepper-resistance-against-tmv
#6
Lei Qin, Ning Mo, Yang Zhang, Tayeb Muhammad, Guiye Zhao, Yan Zhang, Yan Liang
RNA silencing functions as a major natural antiviral defense mechanism in plants. RNA-dependent RNA polymerases (RDRs) that catalyze the synthesis of double-stranded RNAs, are considered as a fundamental element in RNA silencing pathways. In Arabidopsis thaliana, RDR1, 2 and 6 play important roles in anti-viral RNA silencing. Expression of RDR1 can be elevated following plant treatment with defense hormones and virus infection. RDR1 has been studied in several crop species, but not in pepper (Capsicum annuum L...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28701960/role-of-mitochondrial-reverse-electron-transport-in-ros-signaling-potential-roles-in-health-and-disease
#7
REVIEW
Filippo Scialò, Daniel J Fernández-Ayala, Alberto Sanz
Reactive Oxygen Species (ROS) can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28687989/screening-novel-autoantigens-targeted-by-serum-igg-autoantibodies-in-immunorelated-pancytopenia-by-serex
#8
Shanfeng Hao, Rong Fu, Huaquan Wang, Zonghong Shao
Immunorelated pancytopenia (IRP) is characterized by pancytopenia caused by autoantibody-mediated destruction or suppression of bone marrow. However, the autoantigens targeted by autoantibodies in IRP remain unclear. In the present study, we screened novel autoantigens in IRP by serological analysis of recombinant cDNA expression libraries and compared anti-UQCR10 antibody levels between IRP and normal controls detected by immunoblotting. Our results indicate that we successfully constructed the K562 cDNA library, which we used to screen seven candidate autoantigens expressed in haematopoietic cells of IRP: ferritin, light polypeptide, ubiquinol-cytochrome c reductase, complex III subunit X (UQCR10), multifunctional methyl-transferase subunit TRM112-like protein isoform 1 (TRMT112), hemoglobin gamma-G, stathmin 1 (STMN1), transcript variant 3, phosphoglycerate kinase 1 (PGK1), and trafficking protein particle complex subunit 4 (TRAPPC4)...
July 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28684614/ubiquinol-effects-on-antiphospholipid-syndrome-prothrombotic-profile-a-randomized-placebo-controlled-trial
#9
Carlos Pérez-Sánchez, María Ángeles Aguirre, Patricia Ruiz-Limón, María Carmen Abalos-Aguilera, Yolanda Jiménez-Gómez, Iván Arias-de la Rosa, Antonio Rodriguez-Ariza, Lucía Fernández-Del Río, José Antonio Gonzalez-Reyes, Pedro Segui, Eduardo Collantes-Estévez, Nuria Barbarroja, Francisco Velasco, Savino Sciascia, Irene Cecchi, María José Cuadrado, José Manuel Villalba, Chary López-Pedrera
OBJECTIVE: Antiphospholipid syndrome (APS) leukocytes exhibit an oxidative perturbation, directly linked to alterations in mitochondrial dynamics and metabolism. This disturbance is related to the patients' prothrombotic status and can be prevented by in vitro treatment with coenzyme Q10. Our aim was to investigate short-term effects of in vivo ubiquinol (reduced coenzyme Q10[Qred]) supplementation on markers related to inflammation and thrombosis in APS through a prospective, randomized, crossover, placebo-controlled trial...
July 6, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28676853/overexpression-of-ubiquinol-cytochrome-c-reductase-core-protein-1-may-protect-h9c2-cardiac-cells-by-binding-with-zinc
#10
Tingting Yi, Xiaoxiao Wu, Zonghong Long, Guangyou Duan, Zhuoxi Wu, Hong Li, Huifang Chen, Xiaoying Zhou
In several recent studies, proteomics analyses suggest that increase of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is cardio-protective. However, direct evidence for this effect has not yet been obtained. Thus, the current study aimed to determine this effect and the mechanism underlying this effect. The results showed that overexpression of UQCRC1 protected H9c2 cardiac cells against in vitro simulated ischemia-reperfusion by maintaining mitochondrial membrane potential and suppressing the expression of caspase-3...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28634030/effects-of-membrane-curvature-and-ph-on-proton-pumping-activity-of-single-cytochrome-bo3-enzymes
#11
Mengqiu Li, Sanobar Khan, Honglin Rong, Roman Tuma, Nikos S Hatzakis, Lars J C Jeuken
The molecular mechanism of proton pumping by heme-copper oxidases (HCO) has intrigued the scientific community since it was first proposed. We have recently reported a novel technology that enables the continuous characterisation of proton transport activity of a HCO and ubiquinol oxidase from Escherichia coli, cytochrome bo3, for hundreds of seconds on the single enzyme level (Li et al. J Am Chem Soc 137 (2015) 16055-16063). Here, we have extended these studies by additional experiments and analyses of the proton transfer rate as a function of proteoliposome size and pH at the N- and P-side of single HCOs...
June 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28620034/structural-insights-into-the-alternative-oxidases-are-all-oxidases-made-equal
#12
REVIEW
Benjamin May, Luke Young, Anthony L Moore
The alternative oxidases (AOXs) are ubiquinol-oxidoreductases that are members of the diiron carboxylate superfamily. They are not only ubiquitously distributed within the plant kingdom but also found in increasing numbers within the fungal, protist, animal and prokaryotic kingdoms. Although functions of AOXs are highly diverse in general, they tend to play key roles in thermogenesis, stress tolerance (through the management of radical oxygen species) and the maintenance of mitochondrial and cellular energy homeostasis...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28596420/analysis-of-posttranslational-activation-of-alternative-oxidase-isoforms
#13
Jennifer Selinski, Andreas Hartmann, Adrian Kordes, Gabriele Deckers-Hebestreit, James Whelan, Renate Scheibe
Mitochondrial alternative oxidase (AOX) in plants is a non-proton-motive ubiquinol oxidase that is activated by redox mechanisms and 2-oxo acids. A comparative analysis of the AOX isoenzymes AOX1A, AOX1C, and AOX1D from Arabidopsis (Arabidopsis thaliana) revealed that cysteine residues, CysI and CysII, are both involved in 2-oxo acid activation, with AOX1A activity being more increased by 2-oxo acids than that of AOX1C and AOX1D. Substitution of cysteine in AOX1A by glutamate mimicked its activation by pyruvate or glyoxylate, but not in AOX1C and AOX1D...
August 2017: Plant Physiology
https://www.readbyqxmd.com/read/28586052/a-novel-approach-to-select-differential-pathways-associated-with-hypertrophic-cardiomyopathy-based-on-gene-co%C3%A2-expression-analysis
#14
Xiao-Min Chen, Ming-Jun Feng, Cai-Jie Shen, Bin He, Xian-Feng Du, Yi-Bo Yu, Jing Liu, Hui-Min Chu
The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28567017/azoxystrobin-induces-apoptosis-of-human-esophageal-squamous-cell-carcinoma-kyse-150-cells-through-triggering-of-the-mitochondrial-pathway
#15
Xiao-Ke Shi, Xiao-Bo Bian, Tao Huang, Bo Wen, Ling Zhao, Huai-Xue Mu, Sarwat Fatima, Bao-Min Fan, Zhao-Xiang Bian, Lin-Fang Huang, Cheng-Yuan Lin
Recent studies indicate that mitochondrial pathways of apoptosis are potential chemotherapeutic target for the treatment of esophageal cancer. Azoxystrobin (AZOX), a methoxyacrylate derived from the naturally occurring strobilurins, is a known fungicide acting as a ubiquinol oxidation (Qo) inhibitor of mitochondrial respiratory complex III. In this study, the effects of AZOX on human esophageal squamous cell carcinoma KYSE-150 cells were examined and the underlying mechanisms were investigated. AZOX exhibited inhibitory effects on the proliferation of KYSE-150 cells with inhibitory concentration 50% (IC50) of 2...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28562658/new-insight-into-the-mechanism-of-mitochondrial-cytochrome-c-function
#16
Rita V Chertkova, Nadezda A Brazhe, Tatiana V Bryantseva, Alexey N Nekrasov, Dmitry A Dolgikh, Alexander I Yusipovich, Olga Sosnovtseva, Georgy V Maksimov, Andrei B Rubin, Mikhail P Kirpichnikov
We investigate functional role of the P76GTKMIFA83 fragment of the primary structure of cytochrome c. Based on the data obtained by the analysis of informational structure (ANIS), we propose a model of functioning of cytochrome c. According to this model, conformational rearrangements of the P76GTKMIFA83 loop fragment have a significant effect on conformational mobility of the heme. It is suggested that the conformational mobility of cytochrome c heme is responsible for its optimal orientation with respect to electron donor and acceptor within ubiquinol-cytochrome c oxidoreductase (complex III) and cytochrome c oxidase (complex IV), respectively, thus, ensuring electron transfer from complex III to complex IV...
2017: PloS One
https://www.readbyqxmd.com/read/28554565/antioxidant-mechanism-of-mitochondria-targeted-plastoquinone-skq1-is-suppressed-in-aglycemic-hepg2-cells-dependent-on-oxidative-phosphorylation
#17
Jan Ježek, Hana Engstová, Petr Ježek
Previously suggested antioxidant mechanisms for mitochondria-targeted plastoquinone SkQ1 included: i) ion-pairing of cationic SkQ1(+) with free fatty acid anions resulting in uncoupling; ii) SkQ1H2 ability to interact with lipoperoxyl radical; iii) interference with electron flow at the inner ubiquinone (Q) binding site of Complex III (Qi), involving the reduction of SkQ1 to SkQ1H2 by ubiquinol. We elucidated SkQ1 antioxidant properties by confocal fluorescence semi-quantification of mitochondrial superoxide (Jm) and cytosolic H2O2 (Jc) release rates in HepG2 cells...
May 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28538096/location-of-the-substrate-binding-site-of-the-cytochrome-bo3-ubiquinol-oxidase-from-escherichia-coli
#18
Sylvia K Choi, Lici Schurig-Briccio, Ziqiao Ding, Sangjin Hong, Chang Sun, Robert B Gennis
Cytochrome bo3 is a respiratory proton-pumping oxygen reductase that is a member of the heme-copper superfamily that utilizes ubiquinol-8 (Q8H2) as a substrate. The current consensus model has Q8H2 oxidized at a low affinity site (QL), passing electrons to a tightly bound quinone cofactor at a high affinity site (QH site) that stabilizes the one-electron reduced ubisemiquinone, facilitating the transfer of electrons to the redox active metal centers where O2 is reduced to water. The current work shows that the Q8 bound to the QH site is more dynamic than previously thought...
June 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28532810/species-level-identification-of-coagulase-negative-staphylococcus-spp-from-buffalo-using-matrix-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry-and-cydb-real-time-quantitative-pcr
#19
Lucas J L Pizauro, Camila C de Almeida, Glenn A Soltes, Durda Slavic, Oswaldo D Rossi-Junior, Fernando A de Ávila, Luiz F Zafalon, Janet I MacInnes
Incorrect identification of Staphylococcus spp. can have serious clinical and zoonotic repercussions. Accordingly, the aim of this study was to determine if matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and/or cydB real- time quantitative PCR (qPCR) could be used to accurately identify coagulase negative Staphylococcus spp. (CoNS) obtained from buffalo milk and milking environment samples. Seventy-five of 84 CoNS isolates could be identified to the species level (score value >1...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28489094/theoretical-insights-into-the-mechanism-of-ferroptosis-suppression-via-inactivation-of-a-lipid-peroxide-radical-by-liproxstatin-1
#20
Xiehuang Sheng, Chao Shan, Jianbiao Liu, Jintong Yang, Bin Sun, Dezhan Chen
Ferroptosis is a recently discovered iron-dependent form of non-apoptotic cell death caused by the accumulation of membrane lipid peroxidation products, which is involved in various pathological conditions of the brain, kidney, liver and heart. A potent spiroquinoxalinamine derivative named liproxstatin-1 is discovered by high-throughput screening, which is able to suppress ferroptosis via lipid peroxide scavenging in vivo. Thus, molecular simulations, density functional theory (DFT) and variational transition-state theory with a small-curvature tunneling (SCT) coefficient are utilized to elucidate the detailed mechanisms of inactivation of a lipid peroxide radical by liproxstatin-1...
May 24, 2017: Physical Chemistry Chemical Physics: PCCP
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