Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.99.5 (NADH dehydrogenase)
2,135 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated mitochondria supplemented with succinate or NAD(+)-linked substrates generate hydrogen peroxide (H2O2) in State 4 and the generation is enhanced by antimycin A, an inhibitor of the respiratory chain. Superoxide is a stoichiometric precursor of mitochondrial H2O2 because the ratio of O2-/H2O2 generation rates is close to 2.0 and is generated by an autoxidizable component in the NADH dehydrogenase and the ubiquinone-cytochrome b site. Lipid peroxidation is a free radical-mediated degradation of polyunsaturated fatty acids. Lipid-peroxidation reactions by bovine submitochondrial particles are supported by NADH or NADPH in the presence of ADP-Fe3+ chelate. Electrons from NADH are supplied to the reactions from a component between the substrate site and the rotenone-sensitive site of the NADH dehydrogenase. The peroxidation is dependent on the rate of electron input into the respiratory chain and on the concentration of reduced ubiquinone. Alteration of inner-membrane components and damage to electron-transfer activities of submitochondrial particles are induced by lipid peroxidation. 1-Melhyl-4-phenylpyridinium (MPP+), a metabolite of a parkinsonism-inducing drug, induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in submitochondrial particles, indicating that the oxidative stress induced by MPP+ may potentiate its toxicity in dopamine neurons.
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PMID:[Superoxide formation and lipid peroxidation by the mitochondrial electron-transfer chain]. 777 32

Exposure of cells to hydrogen peroxide (H2O2) mediates adaptive responses or oxidative damage, depending on the magnitude of the challenge. Determining the threshold for peroxide-mediated oxidative stress thus requires quantitation of the changes in endogenous H2O2 production. The intracellular steady-state concentrations of H2O2 were measured in intact Escherichia coli under different conditions. Compounds that block electron transport at NADH dehydrogenase (rotenone) or between ubiquinone and cytochrome b (antimycin) showed that univalent reduction of O2 can occur at these sites in vivo to form superoxide anion (O2-), in agreement with reports for mammalian mitochondria. Mutational inactivation of different components of the respiratory chain showed that H2O2 production also depended on the energy status of the cell and on the arrangement of respiratory chain components corresponding to particular growth conditions. Production rates for O2- and H2O2 were linearly related to the number of active respiratory chains that reached maximal values during exponential growth. In the strains defective in respiratory chain components, catalase activity was regulated to compensate for changes in the H2O2 production rates, which maintained intracellular H2O2 at 0.1-0.2 microM during aerobic growth over a wide range of cell densities. The expression of a katG'::lacZ fusion (reporting transcriptional control of the catalase-hydroperoxidase I gene) was increased by H2O2 given either as a pulse or as a steady production. This response not only depended on the type and severity of the stimulus but was also strongly influenced by the growth phase of the cells.
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PMID:Metabolic sources of hydrogen peroxide in aerobically growing Escherichia coli. 777 20

A mitochondrial extract from Leishmania tarentolae directs the incorporation of uridylate (U) residues within the pre-edited domain of synthetic cytochrome b (CYb) and NADH dehydrogenase subunit 7 mRNA. This has several characteristics of an in vitro RNA editing activity, but no direct evidence for involvement of guide RNAs was obtained. Inhibition by micrococcal nuclease suggests a requirement for some type of endogenous RNA. The limitation of internal U-incorporation to the pre-edited region in the CYb mRNA and the inhibition by deletion or substitution of both mRNA anchor sequences for CYb gRNA-I and -II could be consistent either with a gRNA-mediated process or a secondary structure-mediated process. A low level of incorporation of [alpha-32P]CTP occurs at the same sites as UTP. Internal U-incorporation activity is selectively inhibited by heterologous RNAs, suggesting an involvement of low affinity RNA-binding proteins which can be competed by the added RNA.
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PMID:In vitro RNA editing-like activity in a mitochondrial extract from Leishmania tarentolae. 782 90

We have sequenced a segment of mitochondrial DNA (mtDNA) of a crustacean, the brine shrimp, Artemia salina, that includes 3' end-proximal regions of the genes for subunit 1 of the NADH dehydrogenase complex (ND1) and cytochrome b (Cyt b). From our data we conclude that in this mtDNA, as in the mtDNAs of Drosophila species, a tRNA(Ser)(UCN) gene separates the ND1 and Cyt b genes. This is contrary to an earlier report that the A. salina ND1 and Cyt b genes are immediately adjacent to each other.
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PMID:A tRNA(Ser)(UCN) gene in Artemia salina mitochondrial DNA: a case of mistaken identity. 825 41

The objective of this study was to explore the possible cause(s) underlying the previously observed, age-related increase in the rate of mitochondrial H2O2 release in the housefly. The hypothesis that an imbalance between different respiratory complexes may be a causal factor was tested. Cytochrome c oxidase activity was found to sharply decline in the latter part of the life span of the flies. Effects of different substrates and respiratory inhibitors were determined in order to ascertain if a decrease in cytochrome c oxidase activity could be responsible for the increased H2O2 release. H2O2 was measured spectrofluorometrically using horseradish peroxidase and p-hydroxphenylacetate as an indicator. Neither NADH-linked substrates nor succinate caused a stimulation of H2O2 production. H2O2 release by mitochondria, inhibited with rotenone and antimycin A, was greatly increased upon supplementation with alpha-glycerophosphate; however, the further addition of KCN or myxothiazol, to such preparations, caused a depression of H2O2 generation. In contrast, relatively low concentrations of KCN or myxothiazol were found to stimulate H2O2 release in insect mitochondria supplemented with alpha-glycerophosphate and exposed to rotenone, but not antimycin A. Results are interpreted to suggest that partial inhibition of cytochrome c oxidase activity can lead to the stimulation of mitochondrial H2O2 production in the housefly at site(s) other than NADH dehydrogenase and ubisemiquinone/cytochrome b region; a possible source may be glycerophosphate dehydrogenase.
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PMID:Aging, cytochrome oxidase activity, and hydrogen peroxide release by mitochondria. 839 19

Studies were undertaken to investigate the principal actions underlying mercury-induced oxidative stress in the kidney. Mitochondria from kidneys of rats treated with HgCl2 (1.5 mg/kg i.p.) demonstrated a 2-fold increase in hydrogen peroxide (H2O2) formation for up to 6 hr following Hg(II) treatment using succinate as the electron transport chain substrate. No increase in H2O2 formation was observed when NAD-linked substrates (malate/glutamate) were used, suggesting that Hg(II) affects H2O2 formation principally at the ubiquinone-cytochrome b region of the mitochondrial respiratory chain in vivo. Together with increased H2O2 formation, mitochondrial glutathione (GSH) content was depleted by more than 50% following Hg(II) treatment, whereas formation of thiobarbiturate reactive substances (TBARS), indicative of mitochondrial lipid peroxidation, was increased by 68%. Studies in vivo revealed a significant concentration-related depolarization of the inner mitochondrial membrane following the addition of Hg(II) to mitochondria isolated from kidneys of untreated rats. This effect was accompanied by significantly increased H2O2 formation, GSH depletion and TBARS formation linked to both NADH dehydrogenase (rotenone-inhibited) and ubiquinone-cytochrome b (antimycin-inhibited) regions of the electron transport chain. Oxidation of pyridine nucleotides (NAD[P]H) was also observed in mitochondria incubated with Hg(II) in vitro. In further studies in vitro, the potential role of Ca2+ in Hg(II)-induced mitochondrial oxidative stress was investigated. Ca2+ alone (30-400 nmol/mg protein) produced no increase in H2O2 and only a slight increase in TBARS formation when incubated with kidney mitochondria isolated from untreated rats. However, Ca2+ significantly increased H2O2 and TBARS formation elicited by Hg(II) at the ubiquinone-cytochrome b region of the mitochondrial electron transport chain, whereas TBARS formation was decreased significantly when the Ca2+ uptake inhibitors, ruthenium red or [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA), were included with Hg(II) in the reaction mixtures. These findings support the view that Hg(II) causes depolarization of the mitochondrial inner membrane with consequent increased H2O2 formation. These events, coupled with Hg(II)-mediated GSH depletion and pyridine nucleotide oxidation, create an oxidant stress condition characterized by increased susceptibility of mitochondrial membranes to iron-dependent lipid peroxidation (TBARS formation). Since increased H2O2 formation, GSH depletion and lipid peroxidation were also observed in vivo following Hg(II) treatment, these events may underlie oxidative tissue damage caused by mercury compounds. Moreover, Hg(II)-induced alterations in mitochondrial Ca2+ homeostasis may exacerbate Hg(II)-induced oxidative stress in kidney cells.
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PMID:Studies on Hg(II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria. 851 85

The effect of galactosamine on liver mitochondrial functions was studied in vivo in rats at 12hr, 24hr and 36hr after the administration of the drug. State 3 respiration decreased significantly with both NAD+ linked and FAD linked substrates. Respiratory control ratio, an index of membrane integrity and P/O ratio which is a measure of phosphorylation efficiency decreased significantly. There was a significant decrease in the activities of NADH dehydrogenase, succinate dehydrogenase and cytochrome oxidase. A significant decrease was also seen on membrane potential, cytochrome aa3, cytochrome b, cytochrome c and on phospholipids of mitochondria. The observed mitochondrial dysfunctions were related to increased lipid peroxidation, which could cause loss of membrane integrity and a decreased rate of phosphorylation. It is proposed that increased lipid peroxidation was responsible for the inhibition on both oxidation and phosphorylation in mitochondria in galactosamine treated rats.
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PMID:Effect of administration of galactosamine hydrochloride on rat liver mitochondria. 942 49

The nucleotide sequences of two segments of 6,737 ntp and 258 nto of the 18.4-kb circular mitochondrial (mt) DNA molecule of the soft coral Sarcophyton glaucum (phylum Cnidaria, class Anthozoa, subclass Octocorallia, order Alcyonacea) have been determined. The larger segment contains the 3' 191 ntp of the gene for subunit 1 of the respiratory chain NADH dehydrogenase (ND1), complete genes for cytochrome b (Cyt b), ND6, ND3, ND4L, and a bacterial MutS homologue (MSH), and the 5' terminal 1,124 ntp of the gene for the large subunit rRNA (1-rRNA). These genes are arranged in the order given and all are transcribed from the same strand of the molecule. The smaller segment contains the 3' terminal 134 ntp of the ND4 gene and a complete tRNA(f-Met) gene, and these genes are transcribed in opposite directions. As in the hexacorallian anthozoan, Metridium senile, the mt-genetic code of S. glaucum is near standard: that is, in contrast to the situation in mt-genetic codes of other invertebrate phyla, AGA and AGG specify arginine, and ATA specifies isoleucine. However, as appears to be universal for metazoan mt-genetic codes, TGA specifies tryptophan rather than termination. Also, as in M. senile the mt-tRNA(f-Met) gene has primary and secondary structural features resembling those of Escherichia coli initiator tRNA, including standard dihydrouridine and T psi C loop sequences, and a mismatched nucleotide pair at the top of the amino-acyl stem. The presence of a mutS gene homologue, which has not been reported to occur in any other known mtDNA, suggests that there is mismatch repair activity in S. glaucum mitochondria. In support of this, phylogenetic analysis of MutS family protein sequences indicates that the S. glaucum mtMSH protein is more closely related to the nuclear DNA-encoded mitochondrial mismatch repair protein (MSH1) of the yeast Saccharomyces cerevisiae than to eukaryotic homologues involved in nuclear function, or to bacterial homologues. Regarding the possible origin of the S. glaucum mtMSH gene, the phylogenetic analysis results, together with comparative base composition considerations, and the absence of an MSH gene in any other known mtDNA best support the hypothesis that S. glaucum mtDNA acquired the mtMSH gene from nuclear DNA early in the evolution of octocorals. The presence of mismatch repair activity in S. glaucum mitochondria might be expected to influence the rate of evolution of this organism's mtDNA.
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PMID:Mitochondrial DNA of the coral Sarcophyton glaucum contains a gene for a homologue of bacterial MutS: a possible case of gene transfer from the nucleus to the mitochondrion. 954 36

Rates of sequence evolution were estimated for the cytochrome b (cyt b) and NADH dehydrogenase sub-unit 2 (ND2) genes using a phylogeny of the dabbling ducks (Tribe: Anatini) and outgroups. This speciose group was densely sampled, reducing the impact of undetected homoplasy on rate comparisons. Phylogenies based on sequences of the two gene regions and various weighting schemes differed, but most of the differences involved weakly supported nodes. In addition, partition homogeneity tests show that these differences were not due to statistically significant conflict between the data sets. Cyt b and ND2 also showed similar rates and types of both nucleotide and amino acid substitutions. For both genes, substitutions between isoleucine and valine and between alanine and threonine were most common; both of these substitution types are the result of A-G transitions at first positions of codons. Rates of sequence evolution varied substantially and significantly among nucleotide positions, and even within a given codon position (first, second, or third), rates were significantly heterogeneous among sites. Within Anatini, cyt b and ND2 show similar levels of variation and homoplasy, and are equally useful for reconstructing the species level phylogeny of this group.
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PMID:Comparing molecular evolution in two mitochondrial protein coding genes (cytochrome b and ND2) in the dabbling ducks (Tribe: Anatini). 975 19

The participation of oxidative mechanisms in major histocompatibility complex (MHC) class II-restricted antigen presentation was studied in vitro. In general, antigen processing is inhibited when peritoneal macrophages (MO) are incubated with scavengers of reactive oxygen intermediates (ROI): mannitol (an.OH scavenger), dimethylurea (DMTU, which reacts with H2O2 and HOCl) and NCO-700 (an epoxysuccinic acid derivative which inhibits oxidant production by activated phagocytes and can scavenge reactive oxygen species in both NaOCl and hypoxanthine (XOD) systems). However, neither rotenone and antimycins (inhibitors of O-2 production at the NADH dehydrogenase and ubiquinone-cytochrome b regions, respectively) nor aminoguanidine (an inducible nitric oxide synthase inhibitor) impaired antigen presentation, thus indirectly discarding the participation of mitochondrial oxidation and reactive nitrogen intermediates (RNI) in antigen processing. ROI scavengers do not inhibit the MHC class II-restricted presentation of antigens that need processing but have their disulphide bonds reduced. It can be shown that oxidation of protein antigens (either by chlorination or performic acid treatment) allow protein unfolding and enhance both processing and exposure of immunogenic epitopes to specific T cells.
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PMID:Oxidation of defined antigens allows protein unfolding and increases both proteolytic processing and exposes peptide epitopes which are recognized by specific T cells. 982 92


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