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:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reactive microglia in the developing brain after stab wound was studied by morphological, cytochemical, and autoradiographic methods. Morphologically, early reactive cells are of the "M" cell type (Matthews 1974). They show an activated nucleus, cytoplasm rich in ribosomes with wide Golgi complex and variable numbers of lipid inclusions. Big clear vacuoles are found in many of these cells. Microtubules not associated with centrioles and filaments may or may not be present. Junctional complexes of the zonula or puncta adherentia types are occasionally found. Strong NADPH dehydrogenase, weak NADH dehydrogenase, strong ATPase, and strong acid phosphatase, in addition to nonspecific esterase activities were demonstrated in many reactive cells. Intravenous infusion of labelled bone marrow cells from a donor showed labelled macrophages and labelled perivascular cells at the site of injury. Intracerebral injection of a small dose of tritiated thymidine at the time of injury resulted in the appearance of labelled macrophages in the following days. These data suggest that many of the reactive cells have an exogenous, more probably monocytic, origin; but a certain amount of endogenous cells also act as macrophages in brain injuries.
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PMID:Reactive microglia in the developing brain. 737 29

Mitochondria are an important source of reactive oxygen intermediates because they are the major consumers of molecular oxygen in cells. Respiration is associated with toxicity, which is related to the activation of oxygen to reactive intermediates. The purpose of the present study was to examine the role of reduced glutathione (GSH) in the maintenance of mitochondrial functions during oxidative stress induced through selective inhibition of the complex III segment of the electron transport chain. Hydrogen peroxide monitored by the fluorescence of dichlorofluorescein increased in a time- and dose-dependent manner on incubation of mitochondria with antimycin A (AA), an inhibitor of complex III. However, blockade of complex I or II with rotenone or thenoyltrifluoroacetone, respectively, did not result in accumulation of hydrogen peroxide. Depletion of mitochondrial GSH to 10-20% of control by preincubation with diethylmaleate (0.8 mM) or ethacrynic acid (250 microM) also increased dichlorofluorescein and malondialdehyde levels and resulted in an additional (2-3-fold) increase after AA. Similar results were obtained when mitochondrial GSH depletion was produced by treatment with buthionine L-sulfoximine before mirochondria isolation. The endogenous oxidative stress induced by AA was accompanied by a moderate loss of activity of ATPase complex (77% of control) and complex IV of respiration (75% of control), which was accentuated after depletion of mitochondrial GSH (51% and 45% of control, respectively). Similar results were observed in isolated hepatocytes in which depletion of mitochondrial GSH and AA led to peroxidation and mitochondrial dysfunction. In addition, with electrophoretic mobility shift assay of the transcription factor nuclear factor-kappa B (NF-kappa B), we detected its activation in response to AA (2-3-fold). Depletion of mitochondrial GSH in hepatocytes (20% of control) led to further enhancement of NF-kappa B activation (2-4-fold), which correlated with generation of hydrogen peroxide. Thus, our results suggest that GSH protects mitochondria against the endogenous oxidative stress produced at the ubiquinone site of the electron transport chain. Mitochondrial GSH depletion potentiates oxidant-induced loss of mitochondrial functions. Oxidant stress in mitochondria can promote extramitochondrial activation of NF-kappa B and therefore may affect nuclear gene expression.
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PMID:Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes. 747 12

Differential screening of an adrenal cortex cDNA library for corticotropin (ACTH)-inducible genes led to the isolation of a group of cDNAs representing mitochondrial genes that encode subunits of cytochrome oxidase, ATPase, and NADH dehydrogenase. Northern blot analysis of RNA from cells stimulated by ACTH confirmed the induction of these genes by ACTH yet revealed major differences in the relative responses of the respective mRNAs. The levels of mRNAs for cytochrome oxidase subunit I and ATPase increased 2- to 4-fold and for NADH dehydrogenase subunit 3 increased 20-fold, whereas the levels of the mitochondrial 16S rRNA showed no change within 6 h of ACTH stimulation. These effects of ACTH on mitochondrial mRNA levels probably result from both activation of the H2 transcription unit that encodes mitochondrial mRNAs and alteration of mRNA stability. ACTH also increased the activity of cytochrome oxidase after 12 h of stimulation. Examination of the tissue specificity of expression of five mitochondrial genes showed a wide range of RNA levels among 11 tissues but high correlations between individual RNA levels, consistent with a coordinated expression of the mitochondrial genes, although at different levels in each cell type. Proportionately high levels of mitochondrial mRNAs were found in adrenal cortex, probably reflecting a stimulatory effect of ACTH in vivo. Overall, the results indicate that ACTH enhances the energy-producing capacity of adrenocortical cells.
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PMID:Mitochondrial-genome-encoded RNAs: differential regulation by corticotropin in bovine adrenocortical cells. 750 67

Metabolic control analysis was applied to describe the control of mitochondrial oxidative phosphorylation in calcium (approximately 2 microM free calcium) activated saponin-skinned rat musculus soleus fibers oxidizing glutamate and malate. Under these circumstances approximately 80% of mitochondrial active-state respiration was reached due to the activation of ATP turnover by actomyosin ATPase. The flux control coefficients of H(+)-ATPase, adenine-nucleotide translocase, phosphate transporter, NADH:ubiquinone oxidoreductase and cytochrome-c oxidase were determined to be equal to 0.16 +/- 0.08 (n = 6), 0.34 +/- 0.12 (n = 5), 0.08 +/- 0.03 (n = 5), 0.01 +/- 0.006 (n = 4) and 0.09 +/- 0.03 (n = 3) using inhibitor titrations with the specific inhibitors oligomycin, carboxyatractyloside, mersalyl, rotenone and cyanide, respectively, and applying non-linear regression of the entire titration curve. The flux control coefficient of actomyosin ATPase was determined with vanadate to be equal to 0.50 +/- 0.09 (n = 6), measuring independently the vanadate-caused inhibition of fiber respiration and ATP-splitting activity. In contrast to results with isolated rat skeletal muscle mitochondria reconstituted with soluble F1-ATPase the decrease in phosphate concentration from 10 mM to 1 mM only slightly affected the distribution of flux control coefficients. This difference is caused by different kinetic properties of soluble F1-ATPase and actomyosin ATPase. Therefore, phosphate seems to be in skeletal muscle in vivo only a modest modulator of control of oxidative phosphorylation.
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PMID:Distribution of flux control among the enzymes of mitochondrial oxidative phosphorylation in calcium-activated saponin-skinned rat musculus soleus fibers. 760 28

The complete nucleotide sequence of the circular mitochondrial (mt) DNA from the red alga Chondrus crispus was determined (25,836 nucleotides, A+T content 72.1%). Fifty one genes were identified. They include genes encoding three subunits of the cytochrome oxidase (cox1 to 3), apocytochrome b (cob), seven subunits of the NADH dehydrogenase complex (nad1 to 6, nad4L), two ATPase subunits (atp6 and atp9), three ribosomal RNAs (rrn5, srn and lrn), 23 tRNAs and four ribosomal proteins (rps3, rps11, rps12 and rpl16). Two subunits of the succinate dehydrogenase complex (sdhB and sdhC), usually found on nuclear genomes, are also located on the mtDNA of C. crispus. One group IIb intron is inserted in the tRNAIle gene. Six potentially functional open reading frames were identified, four of them having counterparts among green plant mtDNAs. The use of a modified genetic code and the absence of RNA editing, previously reported for the cox3 gene, appears as a general characteristic of this molecule. Mitochondrial genes are encoded on both DNA strands, in two opposite major transcriptional directions, suggesting the existence of two main transcriptional units. Two long and stable stem-loops were identified in intergenic regions, which are believed to be involved with transcription and replication. The main structural features of this genome are compared with the overall organization of mtDNAs and are discussed in view of the evolution of mitochondria.
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PMID:Complete sequence of the mitochondrial DNA of the rhodophyte Chondrus crispus (Gigartinales). Gene content and genome organization. 761 69

Lead, zinc and copper were administered i.p singly or in combination as acetate salts to rats for 14 consecutive days. It was observed that lead induced drastic changes, copper induced moderate changes but zinc did not cause any significant change in the cholesterol and phospholipid content, hexose, hexosamine and sialic acid levels and activities of the erythrocyte membrane enzymes--acetylcholinesterase (AChE), NADH dehydrogenase and Na(+)-K+ ATPase. In the combined metal treatment the presence of zinc considerably reduced the changes induced by lead and copper.
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PMID:Metal induced changes in the erythrocyte membrane of rats. 761 77

Oxidative stress is associated with the formation of oxidized glutathione (GSSG) in the cells, which can form mixed disulfide with proteins leading to alteration of their function. The present study looks at the effect of in vitro exposure of GSSG on intestinal mitochondria and brush border membrane (BBM). Incubation with 1 mM GSSG increased the protein bound GSH in mitochondria by 15-fold. This was associated with loss of activity of certain mitochondrial enzymes such as succinic dehydrogenase, isocitrate dehydrogenase, total ATPase and NADH dehydrogenase whereas NADH oxidase was not affected. A similar treatment of BBMV with GSSG increased the protein bound GSH by 4.7-fold without altering its enzyme activity. Exposure to GSSG had no effect on the Na(+)-dependent glucose transport by BBMV. These studies suggest that GSSG formed during oxidative stress may modify thiol groups in proteins by forming mixed disulfides leading to functional alteration of certain cellular proteins.
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PMID:Effect of oxidized glutathione on intestinal mitochondria and brush border membrane. 767 Nov 37

Changes in the concentrations of intracellular free calcium ([Ca2+]i) and adenine nucleotides were determined in response to metabolic inhibitors in the motoneuron cell line NSC-19. The NADH dehydrogenase inhibitor amobarbital (Amytal) and the mitochondrial uncoupler carbonylcyanide m-chlorophenylhydrazone (CCCP) were used to alter energy metabolism. Exposure of cells to 5 mM Amytal did not significantly change ATP concentrations but produced transient elevations of [Ca2+]i of approximately 80 nM, which were reduced by 32% when cells were studied in Ca(2+)-free solutions. CCCP (10 microM) caused a transient reduction in ATP concentration of 33%. CCCP also produced sustained elevations of [Ca2+]i of about 280 nM, which were reduced by 47% when in Ca(2+)-free solutions. In spite of the sustained elevation of [Ca2+]i induced by CCCP, NSC-19 showed no reduction in cell viability after 48 h compared with controls. Ruthenium red, a blocker of Ca2+ uptake by mitochondria, had little effect on the CCCP-induced [Ca2+]i increment. KCl or glutamate did not produce significant changes in [Ca2+]i, indicating that these cells do not possess significant numbers of voltage-dependent Ca2+ channels or excitatory amino acid receptor-gated channels. [Ca2+]i values in these cells were modified by changes in extracellular Ca2+ concentrations. In Ca(2+)-containing solutions, inhibition of Na+/Ca2+ exchange by amiloride and bepridil led to increased [Ca2+]i, as did blockade of Ca2+ ATPase by vanadate, suggesting that membrane transporters are important in Ca2+ efflux in NSC-19. The present studies indicate that exposure of NSC-19 cells to Amytal and CCCP produces Ca2+ increments by release from internal stores, as well as by transmembrane influx. These results demonstrate that small increments in [Ca2+]i can be produced by metabolic inhibitors or other compounds and that such changes are not associated with immediate cell death. Changes in [Ca2+]i could potentially result in abnormal cell function secondary to altered action of Ca(2+)-dependent enzymes.
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PMID:Intracellular calcium concentrations during metabolic inhibition in the motoneuron cell line NSC-19. 782 81

To understand the mechanism of action of the antitumor arotinoid mofarotene (Ro 40-8757), differential screening of cDNA libraries with cDNA probes prepared from treated or untreated breast-cancer cells was performed. Several genes were identified that appeared to be regulated by mofarotene, including a mitochondrial gene encoding a subunit of NADH dehydrogenase (NDI). This gene was down-regulated in the breast-cancer cell line MDA-MB-231 after treatment with the arotinoid for 3 to 6 hr. Down-regulation of NDI was detected in 2 other breast-carcinoma cell lines (ZR-75-I and MCF-7) and a pancreatic cancer cell line (BxPC3), but not in the normal fibroblast cell line Wi-38 or several other tumor cell lines. This effect was blocked by addition of cycloheximide to the medium. The retinoids, all-trans and 9-cis retinoic acids, did not affect the expression of NDI in MDA-MB-231 cells, demonstrating that mofarotene was not acting through the nuclear retinoic-acid receptors. In the estrogen-receptor-expressing breast-cancer line ZR-75-I, tamoxifen had no effect on NDI expression. The cytotoxic drugs doxorubicin, 5-FU and vincristine also had no effect on regulation of this gene. Two mitochondrial proteins encoded in the nucleus, ATPase beta subunit and mitochondrial transcription factor I, were not down-regulated by mofarotene. Addition of mofarotene to cells incubated in glucose-free medium led to their death. These results indicate that down-regulation of mitochondrial gene transcription is specific to mofarotene and may explain, in part, the anti-proliferative effects of this compound.
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PMID:Down-regulation of mitochondrial gene expression by the anti-tumor arotinoid mofarotene (Ro 40-8757). 792 84

The effects of BRB-I-28 and its derivatives (GLG-V-13, SAZ-VII-22 and SAZ-VII-23), a novel group of antiarrhythmic agents, were investigated on the rat heart mitochondrial respiratory chain. The results indicate that BRB-I-28 and its derivatives have concentration-dependent inhibitory effects on NADH oxidase and NADH-CoQ reductase (complex I), but they have no significant effects on succinate oxidase, succinate dehydrogenase (complex II), CoQ-cytochrome c reductase (complex III), cytochrome c oxidase (complex IV), and NADH-K3Fe(CN)6 reductase. The site of inhibition of BRB-I-28 and its derivatives on the respiratory chain was localized between flavoprotein n (FPn) and CoQ, which is similar to the effect of rotenone and several other antiarrhythmic drugs such as amiodarone, propranolol, etc. BRB-I-28 and its derivatives also have significant inhibitory effects on mitochondrial ATPase activity as reported for other antiarrhythmic drugs such as amiodarone, propranolol, quinidine, and lidocaine. However, BRB-I-28 and its derivatives have no direct effects on sarcoplasmic reticulum Ca(2+)-ATPase activity. The inhibitory effects of BRB-I-28 and its derivatives on mitochondrial oxidative phosphorylation may result in the depletion of ATP. This effect, in combination with their effects on Na+,K(+)-ATPase, could possibly produce an increase in Ca2+ concentration in cytosol. This may be another mechanism by which these DHBCN derivatives produce an increase in systemic arterial blood pressure and contractile force of isolated cardiac muscle. On the other hand, inhibition on mitochondrial respiration may account for some of the potential toxic effects of these diheterabicyclo[3.3.1]nonane derivatives.
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PMID:Effects of novel antiarrhythmic agents, BRB-I-28 and its derivatives, on the heart mitochondrial respiratory chain and sarcoplasmic reticulum Ca(2+)-ATPase. 799 64


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