Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q16795 (ubiquinone)
 5,455 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of purified DT-diaphorase in the reduction of ubiquinone homologues of different side-chain length incorporated in uni- and multilamellar vesicles was determined. The direct relationship between the reduced state of ubiquinones and the inhibition of lipid autoxidation induced by thermolabile azocompounds was also demonstrated. Results demonstrate that DT-diaphorase is able to generate and to maintain the reduced, antioxidant form of ubiquinones in both types of vesicles. Furthermore, the results reported herein show that, in the presence of nicotinamide adenine dinucleotide (NADH) and DT-diaphorase, ubiquinol-containing multilamellar vesicles exposed to a lipophilic azocompound did not undergo lipid peroxidation, whereas in vesicles lacking either NADH or DT-diaphorase, thiobarbituric acid reactive substances (TBARS) formation occurred. It is suggested that DT-diaphorase may be responsible for maintaining the reduced state of ubiquinones in various nonmitochondrial cellular membranes.
 ...
PMID:DT-Diaphorase maintains the reduced state of ubiquinones in lipid vesicles thereby promoting their antioxidant function. 895 58

The inhibitory effect and mechanism of action of nicotinamide to paraquat toxicity were studied in male Sprague-Dawley rats. Proteins of submitochondrial particles (SMP), especially of mol. wt. 25-30 kDa, in rat lungs were destroyed by paraquat radicals, and aggregated protein bands approximately 100 kDa were observed by polyacrylamide electrophoresis. The competitive inhibition effects were observed of nicotinamide on NADH oxidation by paraquat via SMP in rat lungs and the Ki was 9.3 mM. The inhibitory effects of nicotinamide on lipid peroxidation by paraquat with rat lung and liver SMP were verified. The times of occurrence of dyspnea and death in rats after paraquat exposure were delayed by nicotinamide administration. The activity of NADH: ubiquinone reaction of NADH:ubiquinone oxidoreductase (complex I) in rat lung was reduced 24 h after paraquat exposure, and was protected by nicotinamide. The activity of NADH:ferricyanide reaction of complex I was, however, reduced by administration not only of paraquat but also nicotinamide. These results imply that nicotinamide is inhibitory to paraquat toxicity. Nicotinamide, paraquat, and ferricyanide may react at overlapping sites on complex I.
 ...
PMID:Inhibitory effect of nicotinamide to paraquat toxicity and the reaction site on complex I. 933

Our previous studies in iron-loaded rat heart cells showed that in vitro iron loading results in peroxidative injury, manifested in a marked decrease in rate and amplitude of heart cell contractility and rhythmicity, which is correctable by treatment with deferoxamine (DF). In the present studies we explored the role of mitochondrial damage in myocardial iron toxicity. Iron loading by 24-hour incubation with 0.36 mmol/L ferric ammonium citrate resulted in a decrease in the activity of nicotinamide adenine dinucleotide (NADH)-cytochrome c oxidoreductase (complex I+III) to 35.3%+/-11.2% of the value in untreated controls; of succinate-cytochrome c oxidoreductase (complex II+III) to 57.4%+/-3.1%; and of succinate dehydrogenase to 63.5%+/-12.6% (p < 0.001 in all cases). The decrease in activity of other mitochondrial enzymes, including NADH-ferricyanide reductase, succinate ubiquinone oxidoreductase (complex II), cytochrome c oxidase (complex IV), and ubiquinol cytochrome c oxidoreductase (complex III), was less impressive and ranged from 71.5%+/-15.8% to 91.5%+/-14.6% of controls. That the observed loss of respiratory enzyme activity was a specific effect of iron toxicity was clearly demonstrated by the complete restoration of enzyme activities by in vitro iron chelation therapy. Sequential treatment with iron and doxorubicin caused a loss of complex I+III and complex II+III activity that was greater than that seen with either agent alone but was only partially correctable by DF treatment. Alterations in cellular adenosine triphosphate measurements paralleled very closely the changes observed in respiratory complex activity. These findings demonstrate for the first time the impairment of cardiac mitochondrial respiratory enzyme activity caused by iron loading at conditions formerly shown to produce severe abnormalities in contractility and rhythmicity.
 ...
PMID:Mitochondrial respiratory enzymes are a major target of iron toxicity in rat heart cells. 960 12

Reduced nicotinamide adenine dinucleotide (NADH):ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial respiratory chain and complex I deficiency accounts for approximately 30% cases of respiratory-chain deficiency in humans. Only seven mitochondrial DNA genes, but >35 nuclear genes encode complex I subunits. In an attempt to elucidate the molecular bases of complex I deficiency, we studied the six most-conserved complex I nuclear genes (NDUFV1, NDUFS8, NDUFS7, NDUFS1, NDUFA8, and NDUFB6) in a series of 36 patients with isolated complex I deficiency by denaturing high-performance liquid chromatography and by direct sequencing of the corresponding cDNA from cultured skin fibroblasts. In 3/36 patients, we identified, for the first time, five point mutations (del222, D252G, M707V, R241W, and R557X) and one large-scale deletion in the NDUFS1 gene. In addition, we found six novel NDUFV1 mutations (Y204C, C206G, E214K, IVS 8+41, A432P, and del nt 989-990) in three other patients. The six unrelated patients presented with hypotonia, ataxia, psychomotor retardation, or Leigh syndrome. These results suggest that screening for complex I nuclear gene mutations is of particular interest in patients with complex I deficiency, even when normal respiratory-chain-enzyme activities in cultured fibroblasts are observed.
 ...
PMID:Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency. 1134 33

Tumor necrosis factor (TNF)-alpha increases mitochondrial reactive oxygen species (ROS) production in tumor cells and hepatocytes. However, whether TNF-alpha stimulates mitochondrial ROS production in endothelial cells (EC) has not yet been reported. We studied the effect of TNF-alpha on mitochondrial ROS generation in EC and the signaling pathways involved. Cultured human umbilical vein EC (HUVEC) were studied by fluorescence microscopy, using dichlorodihydrofluorescein diacetate (DCFH-DA) as a marker of ROS production and propidium iodide uptake for cell viability. TNF-alpha increased DCFH oxidation in HUVEC dose-dependently. To determine the source of ROS, the mitochondrial respiratory chain inhibitors rotenone + thenoyltrifluoroacetone (TTFA), which inhibit electron entry to ubiquinone, and antimycin A (AA), a blocker of ubisemiquinone, were used. Rotenone and TTFA inhibited (n = 7, P < 0.05), whereas AA increased (118% in 3 min; n = 4, P < 0.01) ROS generation in HUVEC. In contrast, ROS production was not abolished by the nicotinamide adenine dinucleotide phosphate-dependent oxidase inhibitor diphenylene iodonium, by the xanthine oxidase inhibitor allopurinol, nor by the nitric oxide and cyclooxygenase pathway inhibitors N(omega)-nitro-L-arginine and mefenamic acid. In addition, TNF-alpha-induced ROS production was inhibited by the acidic sphingomyelinase inhibitor desipramine (5 microM; -80%, n = 4, P < 0.01) and totally blocked by the ceramide-activated protein kinase (CAPK) inhibitor dimethylaminopurine (1 mM; n = 6, P < 0.05). Thus, TNF-alpha induces mitochondrial ROS production in HUVEC that primarily occurs at the ubisemiquinone site and is mediated by ceramide-dependent signaling pathways involving CAPK.
 ...
PMID:Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide. 1141 43

We present here a series of high-density maps of single-nucleotide polymorphisms (SNPs) detected in genes encoding three organic-anion transporters, three organic anion-transporting polypeptides, and three nicotinamide adenine dinucleotide, reduced:ubiquinone oxidoreductase flavoproteins. A total of 258 SNPs were identified among these nine genes through systematic screening of DNA from 48 Japanese individuals: 17 in 5' flanking regions, three in 5' untranslated regions, 13 in coding regions, 211 in introns, six in 3' untranslated regions, and 8 in 3' flanking regions. By comparing our data with SNPs deposited in the dbSNP database in the National Center for Biotechnology Information, we determined that 236 (91.5%) were novel. In addition, 46 genetic variations of other types were discovered within these loci. These high-resolution maps will serve as a useful resource for analyzing potential associations between variations in these nine genes and differences in human susceptibilities to common diseases or response to drug therapies.
 ...
PMID:Catalog of 258 single-nucleotide polymorphisms (SNPs) in genes encoding three organic anion transporters, three organic anion-transporting polypeptides, and three NADH:ubiquinone oxidoreductase flavoproteins. 1172 87

The purpose of these studies was to examine the role of gene expression in methamphetamine (METH)-induced dopamine (DA) neurotoxicity. First, the effects of the mRNA synthesis inhibitor, actinomycin-D, and the protein synthesis inhibitor, cycloheximide, were examined. Both agents afforded complete protection against METH-induced DA neurotoxicity and did so independently of effects on core temperature, DA transporter function, or METH brain levels, suggesting that gene transcription and mRNA translation play a role in METH neurotoxicity. Next, microarray technology, in combination with an experimental approach designed to facilitate recognition of relevant gene expression patterns, was used to identify gene products linked to METH-induced DA neurotoxicity. This led to the identification of several genes in the ventral midbrain associated with the neurotoxic process, including genes for energy metabolism [cytochrome c oxidase subunit 1 (COX1), reduced nicotinamide adenine dinucleotide ubiquinone oxidoreductase chain 2, and phosphoglycerate mutase B], ion regulation (members of sodium/hydrogen exchanger and sodium/bile acid cotransporter family), signal transduction (adenylyl cyclase III), and cell differentiation and degeneration (N-myc downstream-regulated gene 3 and tau protein). Of these differentially expressed genes, we elected to further examine the increase in COX1 expression, because of data implicating energy utilization in METH neurotoxicity and the known role of COX1 in energy metabolism. On the basis of time course studies, Northern blot analyses, in situ hybridization results, and temperature studies, we now report that increased COX1 expression in the ventral midbrain is linked to METH-induced DA neuronal injury. The precise role of COX1 and other genes in METH neurotoxicity remains to be elucidated.
 ...
PMID:Changes in gene expression linked to methamphetamine-induced dopaminergic neurotoxicity. 1175 11

The steady-state activity of the two quinol-oxidizing pathways of Acanthamoeba castellanii mitochondria, the phosphorylating cytochrome pathway (i.e. the benzohydroxamate(BHAM)-resistant respiration in state 3) and the alternative oxidase (i.e. the KCN-resistant respiration), is shown to be fixed by ubiquinone (Q) pool redox state independently of the reducing substrate (succinate or exogenous reduced nicotinamide adenine dinucleotide (NADH)), indicating that the active Q pool is homogenous. For both pathways, activity increases with the Q reduction level (up to 80%). However, the cytochrome pathway respiration partially inhibited (about 50%) by myxothiazol decreases when the Q reduction level increases above 80%. The decrease can be explained by the Q cycle mechanism of complex III. It is also shown that BHAM has an influence on the relationship between the rate of ADP phosphorylation and the Q reduction level when alternative oxidase is active, and that KCN has an influence on the relationship between the alternative oxidase activity and the Q reduction level. These unexpected effects of BHAM and KCN observed at a given Q reduction level are likely due to functional connections between the two pathways activities or to protein-protein interaction.
 ...
PMID:Interactions between the cytochrome pathway and the alternative oxidase in isolated Acanthamoeba castellanii mitochondria. 1186 Jan 78

Cytokine-mediated regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) non-hypoxic stabilization, translocation and activation is not well characterized. Furthermore, evidence that reactive oxygen species (ROS) signaling mediates interleukin (IL)-1 beta-dependent regulation of HIF-1 alpha has yet to be ascertained in alveolar epithelial cells. Recombinant human IL-1 beta induced, in a time-dependent manner, the nuclear translocation of HIF-1 alpha, an effect associated with up-regulating the activity of this transcription factor under normoxic conditions. In addition, analysis of the mode of action of IL-1 beta revealed a novel induction of intracellular ROS, including hydrogen peroxide (H(2)O(2)), the superoxide anion (O(2)(-*)) and the hydroxyl radical (*OH). The antioxidants, dimethyl sulfoxide (DMSO) and 1,3-dimethyl-2-thiourea (DMTU), purported to be prototypical scavengers of H2O2 and *OH, attenuated, in a dose-dependent manner, IL-1 beta-induced HIF-1 alpha nuclear translocation and activation. The NADPH-oxidase inhibitor, 4'-hydroxy-3'-methoxy-acetophenone (HMAP), which may affect mitochondrial ROS production, attenuated IL-1 beta-mediated nuclear translocation and activation of HIF-1 alpha. Inhibition of the mitochondrion complex I nicotinamide adenine dinucleotide phosphate-dependent oxidase by diphenylene iodonium (DPI), which blocks the conversion of ubiquinone --> ubiquinol, abrogated IL-1 beta-dependent nuclear translocation and activation of HIF-1 alpha. Similarly, interrupting the respiratory chain with potassium cyanide reversed the excitatory effect of IL-1 beta on HIF-1 alpha nuclear translocation and activation. These results indicate that a non-hypoxic pathway mediates cytokine-dependent regulation of HIF-1 alpha translocation and activation in a ROS-sensitive mechanism.
 ...
PMID:Recombinant human interleukin (IL)-1 beta-mediated regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) stabilization, nuclear translocation and activation requires an antioxidant/reactive oxygen species (ROS)-sensitive mechanism. 1210 Oct 82

The efficacy and safety of ubiquinone (Q10) and nicotinamide were evaluated in a 6-month open-label trial in patients with the 3243A-->G mitochondrial DNA mutation. Blood lactate and pyruvate concentrations decreased, but there was little clinical improvement. Q10 and nicotinamide were well tolerated, but two patients died suddenly and unexpectedly during the trial. These deaths may have been unrelated to treatment. The unpredictable course of the disease makes evaluation of the clinical response difficult.
 ...
PMID:Ubiquinone and nicotinamide treatment of patients with the 3243A-->G mtDNA mutation. 1239 67


<< Previous 1 2 3 4 5 6 7 8 9 Next >>