bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embryo/fetal development in cynomolgus monkeys exposed to natalizumab, an α4 integrin inhibitor
Authors: Wehner Nancy G. , Shopp George , Oneda Satoru , Clarke Janet 
Published: April 2009

AbstractBACKGROUND: Natalizumab is a humanized monoclonal immunoglobulin G4 antibody to human α4 integrin that binds to the α4 subunit of α4β1 and α4β7 integrins, where it blocks the interaction of these integrins with their ligands, including fibronectin, vascular cell adhesion molecule‐1, and mucosal addressin cellular adhesion molecule‐1. Because α4 integrins and their ligands appear to be involved in mammalian fetal development, it is possible that natalizumab may interfere with these processes. METHODS: The effects of natalizumab on fetal development were assessed in cynomolgus monkeys at doses of 0, 3, 10, and 30 mg/kg administered intravenously every other day from gestational day (GD) 20 to 70. Pregnancies were terminated by Cesarean section at GD 100. RESULTS: Natalizumab treatment was not associated with increased abortions. All fetuses were alive. No external, visceral, or skeletal abnormalities were seen that were considered to be related to treatment with natalizumab. No histopathological findings were seen in the heart, a target organ of developmental toxicity with a small molecule inhibitor of α4 integrin. At dose levels ≥10 mg/kg, hematological and/or lymphoid effects were observed in some fetuses, consisting of slight thymic atropy, increased extramedullary hematopoiesis in the spleen with a corresponding decrease in the liver, increases in WBC and nucleated RBC, decreases in RBC parameters, and decreases in lymphoid CD20 staining. CONCLUSION: Natalizumab had no abortifacient or teratogenic effects, but was associated with changes in fetal hematopoiesis and leukocyte trafficking. Birth Defects Res (Part B)86: 117‐130, 2009. © 2009 Wiley‐Liss, Inc.
Cytoprotective effect of Artemisia capillaris fractions on oxidative stress‐induced apoptosis in V79 cells
Authors: Hong Jung‐Hee , Lee In‐Seon 
Published: April 2009

AbstractThe objectives of this study were to determine the effects of Artemisia capillaris on the viability, antioxidant status, and cytoprotective against oxidative stress induced by hydrogen peroxide in V79 cells. Pretreatment with ethyl acetate fraction increased 363% cell viability compared to the positive control (PC). The ethyl acetate fraction of A. capillaris scavenged intracellular reactive oxygen species (ROS) and increased the activities of cellular antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GSH‐px), and catalase (CAT), and also increased glutathione (GSH) content. It thereby prevented lipid peroxidation which was demonstrated by the inhibition of the formation of thiobarbituric acid reactive substance (TBARS). Furthermore, ethyl acetate fraction reduced the apoptotic cells and cell cycle arrest at G2/M phase induced by H2O2. These findings suggest that A. capillaris ethyl acetate fraction protected V79 cells against H2O2 damage, by enhancing the antioxidative activity. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Luteolin inhibits adipogenic differentiation by regulating PPARγ activation
Authors: Park Hee‐Sook , Kim Soon‐Hee , Kim Young Sup , Ryu Shi Yong , Hwang Jin‐Taek , Yang Hye Jeong , Kim Gun‐Hee , Kwon Dae Young , Kim Myung‐Sunny 
Published: April 2009

AbstractLuteolin (3′,4′,5,7‐tetrahydroxyflavone), a flavonoid, has been known to possess antimutagenic, antitumorigenic, antioxidant, and anti‐inflammatory properties. In this study, we investigated the role of luteolin in the regulation of adipogenic differentiation in 3T3‐L1 preadipocytes. Luteolin inhibited intracellular triglyceride accumulation in a dose‐dependent manner without cytotoxicity. Western blot and reverse transcription‐polymerase chain reaction analyses showed that this inhibition was accompanied by attenuated expression of the adipogenic transcription factors: peroxisome proliferator‐activated receptor γ (PPARγ) and CCAAT/enhancer‐binding protein α. Luteolin inhibited the PPARγ transactivation stimulated by rosiglitazone, a synthetic agonist, in COS‐7 cells and inhibited rosiglitazone‐induced adipogenic differentiation in 3T3‐L1 cells. These data suggest that luteolin exerts antiadipogenic effects by suppressing adipogenic transcription factors and by inhibiting the transactivation of PPARγ. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
The evolution of coenzyme Q
Authors: Crane Frederick L. 
Published: April 2009

AbstractIn the 50 years since the identification of coenzyme Q as an electron carrier in mitochondria, it has been identified with diverse and unexpected functions in cells. Its discovery came as a result of a search for electron carriers in mitochondria following the identification of flavin and cytochromes by Warburg, Keilin, Chance and others. As a result of investigation of membrane lipids at D.E. Green's laboratory at University of Wisconsin coenzyme Q was identified as the electron carrier between primary flavoprotein dehydrogenases and the cytochromes. Then Peter Mitchell identified the role of transmembrane proton transfer as a basis for ATP synthesis. The general distribution of coenzyme Q in all cell membranes then led to the recognition of a role as a primary antioxidant. The protonophoric function was extended to acidification of Golgi and lysosomal vericles. A further role in proton release through the plasma membrane and its relation to cell proliferation has not been fully developed. A role in generation of H2 O2 as a messenger for hormone and cytokine action is indicated as well as prevention of apoptosis by inhibition of ceramide release. Identification of the genes and proteins required for coenzyme Q synthesis has led to a basis for defining deficiency. For 50 years Karl Folkers has led the search for deficiency and therapeutic application. The development of large scale production, better formulation for uptake, and better methods for analysis have furthered this search. The story isn't over yet. Questions remain about effects on membrane structure, breakdown and control of cellular synthesis and uptake and the basis for therapeutic action.
Mitochondrial production of reactive oxygen species: Role of Complex I and quinone analogues
Authors: Fato Romana , Bergamini Christian , Leoni Serena , Lenaz Giorgio 
Published: April 2009

AbstractMitochondrial reactive oxygen species (ROS) are mainly produced by the respiratory chain enzymes. The sites for ROS production in mitochondrial respiratory chain are normally ascribed to the activity of Complex I and III. The presence of specific inhibitors modulates reactive oxygen species production in Complex I: inhibitors such as rotenone induce a strong ROS increase, while inhibitors such as stigmatellin prevent it. We have investigated the effect of hydrophilic quinones on Complex I ROS production in presence of different inhibitors. Some short chain quinones are Complex I inhibitors (CoQ2, idebenone and its derivatives), while CoQ1, decylubiquinone (DB) and duroquinone (DQ) are good electron acceptors from Complex I.Our results show that the ability of short chain quinones to induce an oxidative stress depends on the site of interaction with Complex I and on their physical‐chemical characteristics. We can conclude that hydrophilic quinones may enhance oxidative stress by interaction with the electron escape sites on Complex I while more hydrophobic quinones can be reduced only at the physiological quinone reducing site without reacting with molecular oxygen.
NAD(P)H:quinone oxidoreductase (NQO1) loss of function in Burkitt's lymphoma cell lines
Authors: Brugè Francesca , Virgili Samantha , Cacciamani Tiziana , Principi Federica , Tiano Luca , Littarru Gian Paolo 
Published: April 2009

AbstractTwo‐electron reduction of quinones catalyzed by NAD(P)H:quinone oxidoreductase (NQO1) protects cells against oxidative stress and toxic quinones. In fact, low level of NQO1 activity is often associated with increased risk of developing different types of tumours and with toxic effects linked to environmental quinones. In a previous report we analyzed the relationship between the oxidative stress induced by UV radiation and CoQ10 content in Burkitt's lymphoma cell lines compared to HL‐60. The basal content of CoQ10 in Raji cells was slightly higher compared to HL‐60. Moreover, after irradiation or ubiquinone supplementation in the medium, reduced CoQ10 levels were higher in Raji and Daudi cells compared to HL‐60. In the present work, in order to inquire if NQO1 plays a role in the CoQ reducing capacity observed in the lymphoblastoid cell lines, we analyzed the transcription and translation products of this gene in Raji and Daudi cells, compared to cell lines possessing low and high NQO1 activity.The amount of transcripts of this gene in lymphoblastoid cells was comparable to that observed in HL‐60 cells (low activity), as well as the level of two alternatively spliced mRNAs; one of which is described for the first time in this work. From the genotype analysis of polymorphisms C609T and C465T we observed that HL‐60, Raji and Daudi cells were all heterozygous. Furthermore, NQO1 enzyme activity and protein synthesis in the cytosol of Raji and Daudi cells were undetectable. Therefore in Burkitt's lymphoma cell lines the NQO1 gene is not efficiently translated and this effect is not related to (C609T) polymorphism. Further studies will be necessary to find the enzyme responsible for CoQ10 reducing activity observed in lymphoma cell lines. On the other hand, this result suggests a careful re‐evaluation of data concerning loss of NQO1 activity and polymorphisms in tumour cells.
Ubichromanol: A prodrug to support mitochondrial ubiquinone functions?
Authors: Gille Lars , Stamberg Werner , Gregor Wolfgang , Jäger Walter , Reznicek Gottfried , Netscher Thomas , Rosenau Thomas , Nohl Hans 
Published: April 2009

AbstractUbichromanol‐9 (UCa9, with a side chain consisting of nine isoprene units) is a reductive cyclization product of ubiquinone‐10 (UQ10). It acts as a radical scavenging antioxidant and is about half as effective as α‐tocopherol. Already decades ago its one‐electron oxidation product, the ubichromanoxyl radical had been identified. However, nothing was known so far about the two‐electron oxidation product of this antioxidant and its bioactivity. This study proves that ubichromanol can be oxidized to a ubiquinone‐like compound with a hydroxyl‐substituted side chain (UQ10 OH), a metabolite that is naturally present in bovine liver mitochondria.The bioactivity of this ubiquinone derivative in its reduced form as substrate for mitochondrial complex III (cytochrome bc1 complex) was slightly below that of native ubiquinol, but significantly higher than that of reduced α‐tocopheryl quinone. Since ubiquinone‐like molecules (UQ10 OH, UQ10) were identified as oxidation products of UCa9 during lipid peroxidation, this ubiquinone derivative could provide a possibility to combine antioxidant properties of chromanols and bioenergetic benefits of UQ10.
Supplemental ubiquinol in patients with advanced congestive heart failure
Authors: Langsjoen Peter H. , Langsjoen Alena M. 
Published: April 2009

AbstractPatients with CHF, NYHA class IV, often fail to achieve adequate plasma CoQ10 levels on supplemental ubiquinone at dosages up to 900 mg/day. These patients often have plasma total CoQ10 levels of less than 2.5 μg/ml and have limited clinical improvement. It is postulated that the intestinal edema in these critically ill patients may impair CoQ10 absorption. We identified seven patients with advanced CHF (mean EF 22%) with sub‐therapeutic plasma CoQ10 levels with mean level of 1.6 μg/ml on an average dose of 450 mg of ubiquinone daily (150–600 mg/day). All seven of these patients were changed to an average of 580 mg/day of ubiquinol (450–900 mg/day) with follow‐up plasma CoQ10 levels, clinical status, and EF measurements by echocardiography. Mean plasma CoQ10 levels increased from 1.6 μg/ml (0.9–2.0 μg/ml) up to 6.5 μg/ml (2.6–9.3 μg/ml). Mean EF improved from 22% (10–35%) up to 39% (10–60%) and clinical improvement has been remarkable with NYHA class improving from a mean of IV to a mean of II (I to III). Ubiquinol has dramatically improved absorption in patients with severe heart failure and the improvement in plasma CoQ10 levels is correlated with both clinical improvement and improvement in measurement of left ventricular function.
Oxidative stress, endothelial function and coenzyme Q10
Authors: Belardinelli Romualdo , Tiano Luca , Littarru Gian Paolo 
Published: April 2009

AbstractReactive oxygen species seem to play an important role in vascular homeostasis. In conditions of high oxidative stress, such as chronic heart failure and multiple coronary risk factors, the rate of inactivation of nitric oxide to peroxynitrite by superoxide anions may be reduced by CoQ10, which can also protect against nitrosative damage. CoQ10 may also influence vascular function indirectly via inhibition of oxidative damage to LDL. Patients with lower levels of extracellular superoxide dismutase (ecSOD) demonstrate greater improvements than patients with normal ec‐SOD levels, suggesting that the higher the oxidative stress the greater the improvement in the endothelium‐dependent relaxation after the administration of a compound with antioxidant properties like CoQ10. Future studies are needed to inquire whether these effects may translate into benefits in clinical practice.
Antiangiogenic and hypolipidemic activity of coenzyme Q10 supplementation to breast cancer patients undergoing Tamoxifen therapy
Authors: Sachdanandam Panchanatham 
Published: April 2009

AbstractTamoxifen, a non‐steroidal anti‐estrogen is now widely used and has led to an increase in both disease‐free and overall survival of women after primary surgery. Tamoxifen therapy is found to cause hypertriglyceridemia by reducing activity of lipolytic enzymes on triglycerides, and thereby increasing the risk of cardiovascular disease. Angiogenesis promotes local tumour progression and invasion and enables tumour cell dissemination and metastasis formation. Our study has found that co‐administration of Coenzyme Q10 (100 mg) along with tamoxifen (10 mg, twice a day) to breast cancer patients reduced the level of angiogenesis markers and lipid levels.
arNOX activity of saliva as a non‐invasive measure of coenzyme Q10 response in human trials
Authors: Morré D. James , Morré Dorothy M. 
Published: April 2009

AbstractarNOX is a coenzyme Q10‐inhibited, aging‐related ECTO‐NOX protein of the cell surface also present in sera. It is capable of Superoxide generation measured as Superoxide dismutase‐inhibited reduction of ferricytochrome c and is a potential contributor to atherogenic risk. Here, we report an arNOX activity of saliva of older individuals also inhibited by coenzyme Q10. The activity first appears after age 30 to a near maximum at about age 55. Those surviving beyond age 55 usually have reduced arNOX activities. Our studies demonstrate significant (25 to 30%) reduction of arNOX levels with coenzyme Q10 supplementation of 60 mg (2 × 30 mg) per day for 28 days. Activity correlated with age. Response to coenzyme Q10 increased with age being greatest between ages 60 and 65. Saliva arNOX levels varied in a regular pattern throughout the day so it was important that samples be collected at approximately the same time each day for comparative purposes. The coenzyme Q10 response was reversible and within 12 h after the last intake of coenzyme Q10, the salivary arNOX levels returned to base line. The findings suggest that salivary arNOX provides a convenient and non‐invasive method to monitor arNOX levels in clinical coenzyme Q10 intervention trials with the response levels paralleling those seen with serum and cellular arNOX.
Mechanisms of inhibitory effects of CoQ10 on UVB‐induced wrinkle formation in vitro and in vivo
Authors: Inui M. , Ooe M. , Fujii K. , Matsunaka H. , Yoshida M. , Ichihashi M. 
Published: April 2009

AbstractPhotodamaged skin exhibits wrinkles, pigmented spots, dryness and tumors. Solar UV radiation induces cyclobutane pyrimidine dimers (CPD) and further produces base oxidation by reactive oxygen species (ROS). ROS are thought to be a major factor to initiate the up‐regulation of matrix metalloproteinases (MMPs) in keratinocytes and fibroblasts via activation of receptor proteins on the cell membrane of keratinocytes and fibroblasts, and to degrade fiber components in dermis, leading to wrinkle formation.Coenzyme Q10 (CoQ10) was reported to reduce ROS production and DNA damage triggered by UVA irradiation in human keratinocytes in vitro. Further, CoQ10 was shown to reduce UVA‐induced MMPs in cultured human dermal fibroblasts. We speculated that UVB radiation‐induced cytokine production in keratinocytes may be inhibited by CoQ10, resulting in the reduction of MMPs in fibroblasts leading to wrinkle reduction. Our in vitro studies showed that UVB‐induced IL‐6 production of normal human keratinocyte (NHKC) decreased in the presence of CoQ10. Furthermore, MMP‐1 production of fibroblasts cultured with the medium containing CoQ10 collected from UVB‐irradiated NHKC significantly decreased during 24 h culture. In the clinical trial study, we found that the use of 1% CoQ10 cream for five months reduced wrinkle score grade observed by a dermatologist. Taken together, our results indicate that CoQ10 may inhibit the production of IL‐6 which stimulate fibroblasts in dermis by paracrine manner to up‐regulate MMPs production, and contribute to protecting dermal fiber components from degradation, leading to rejuvenation of wrinkled skin.
Improved HPLC column‐switching determination of coenzyme Q and Vitamin E in plasma
Authors: Bompadre Stefano , Tulipani Sara , Romandini Stefania , Giorgetti Raffaele , Battino Maurizio 
Published: April 2009

AbstractA novel isocratic modified column‐switching HPLC method for automated quantitative analysis of Vitamin E and Coenzyme Q, in the reduced and oxidized form, is described. Many column‐switching HPLC methods are found in the literature, also for determining antioxidant substances, but we developed a different system of column‐switching. An empty column, 5 cm long, was connected to the switching valve, before the sample loop and the extraction column. The sample loop was connected directly after the empty column. The inserted column, containing about 1.4 ml of the extraction eluent simulated a gradient elution, enhancing sensitivity and resolution. When switching the columns, the empty column is placed right before the extraction column and acts as a static mixer for the extraction phase and the incoming analytical phase. Samples were cleaned from interfering compounds by transfer onto a extraction‐column, using a C‐8 silica. Separation was performed onto an analytical column C18 3 μm, 150 mm × 4.6 mm at a flow rate of 1.0 ml/min with 20 mmol/l lithium perchlorate/perchloric acid, pH3.0 in Ethanol as analytical eluent. Detection was performed with a ESA Coulochem 5100 A model. The method was found to be suitable for automated analysis of Coenzyme Q, reduced and oxidized form, and Vitamin E in serum.
Movements at the hemoglobin A‐hemes and their role in ligand binding, analyzed by X‐ray crystallography
Authors: Dodson Eleanor , Dodson Guy 
Published: April 2009

AbstractThe two hemoglobin structures determined by Max Perutz, the liganded R‐state, which has high oxygen affinity, and the unliganded T‐state with low oxygen affinity, were landmarks in molecular and structural biology (Perutz and Lehman, Nature 1968, 219, 902–909; Bolton and Perutz, Nature 1970, 28, 551–552; Perutz et al., Nature 1968, 219, 131–139). They provided the basis of a structural mechanism that connected beautifully to the theory of cooperativity in protein systems, formulated at about the same time by Monod et al. (J Mol Biol 1965, 12, 88–1118). Over the last 40 years there have been extensive biochemical and structural studies on hemoglobin's structure and the mechanisms that govern its co‐operativity, specificity, and other physiological properties. There are still however a number of unresolved issues over the molecule's properties, for example the mechanism responsible for the affects of pH on oxygen affinity, i.e., the Bohr and Root effects. In this communication the differences in the geometry at the a‐heme of unliganded and liganded human and the Antarctic fish (Trematomus) hemoglobin will be described and their relevance to affinity considered. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 1056–1063, 2009.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Glycerol‐induced folding of unstructured disulfide‐deficient lysozyme into a native‐like conformation
Authors: Sakamoto Keiko , Hirai Ken‐ichi , Kitamura Yoshiaki , Yamazaki Kouta , Yusa Mitsunobu , Tokunaga Naoki , Doi Gakuji , Noda Yasuo , Tachibana Hideki , Segawa Shin‐ichi 
Published: April 2009

Abstract2SS[6‐127,64‐80] variant of lysozyme which has two disulfide bridges, Cys6‐Cys127 and Cys64‐Cys80, and lacks the other two disulfide bridges, Cys30‐Cys115 and Cys76‐Cys94, was quite unstructured in water, but a part of the polypeptide chain was gradually frozen into a native‐like conformation with increasing glycerol concentration. It was monitored from the protection factors of amide hydrogens against H/D exchange. In solution containing various concentrations of glycerol, H/D exchange reactions were carried out at pH* 3.0 and 4°C. Then, 1H‐15N‐HSQC spectra of partially deuterated protein were measured in a quenching buffer for H/D exchange (95% DMSO/5% D2O mixture at pH* 5.5 adjusted with dichloroacetate). In a solution of 10% glycerol, the protection factors were nearly equal to 10 at most of residues. With increasing glycerol concentration, some selected regions were further protected, and their protection factors reached about a 1000 in 30% glycerol solution. The highly protected residues were included in A‐, B‐, and C‐helices and β3‐strand, and especially centered on Ile 55 and Leu 56. In 2SS[6‐127,64‐80], long‐range interactions were recovered due to the preferential hydration by glycerol in the hydrophobic box of the α‐domain. Glycerol‐induced recovering of the native‐like structure is discussed from the viewpoint of molten globules growing with the protein folding. © 2009 Wiley Periodicals, Inc. Biopolymers 91: 665–675, 2009.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com