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:1.3.5.1 (succinate dehydrogenase)
8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The formation of liquid-crystalline dispersions (L.C.D.) from double-stranded DNA and polynucleotide (NA) molecules complexed with a number of anthracycline derivatives was investigated. These drugs form two types of complexes (complex I and complex II) with NA, which differ in the mode of drug orientation in respect to the NA helical axis. When complex II forms, addition of copper ions causes bridging of neighboring NA molecules through polymeric copper-anthracycline links (Figure 1). This results in an extra-increase in the amplitude of the intense CD band, characteristic for complex II, in the drug absorption region. Comparison of data obtained for different analogs and derivatives of daunomycin, has shown that the presence of 4 coordinating oxygen atoms at positions 5,6 and 11,12 (or 1,12) of the anthracycline ring system represents the basic prerequisite for the formation of a long polymeric chelate bridge after addition of copper ions. A second requirement relates to the chemical and stereochemical properties of sugar residues at position 7. These are important for proper positioning of the neighboring anthracycline aglycones in the polymeric chelate bridges and for spatial fixation of Cu2+ ions. Base sequence of double-stranded polynucleotides plays, if any, a minor role in polymeric chelate bridge formation. The question concerning the sterical orientation of two neighbouring antracyclines in the linking bridges, formed between NA molecules fixed in the liquid-crystalline structure, remains open.
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PMID:Liquid-crystalline structure of nucleic acids: effect of antracycline drugs and copper ions. 928 83

The perikaryal Purkinje cell mitochondria positive to the copper ferrocyanide histochemical reaction for succinic dehydrogenase (SDH) have been investigated by means of semiautomatic morphometric methods in rats of 3, 12 and 24 months of age. The number of organelles/microm3 of Purkinje cell cytoplasm (Numeric density: Nv), the average mitochondrial volume (V) and the mitochondrial volume fraction (Volume density: Vv) were the ultrastructural parameters taken into account. Nv was significantly higher at 12 than at 3 and 24 months of age. V was significantly decreased at 12 and 24 months of age, but no difference was envisaged between adult and old rats. Vv was significantly decreased in old animals vs. the other age groups. In young and old rats, the percentage of organelles larger than 0.32 microm3 was 13.5 and 11%, respectively, while these enlarged mitochondria accounted for less than 1% in the adult group. Since SDH activity is of critical importance when energy demand is high, the marked decrease of Vv supports an impaired capacity of the old Purkinje cells to match actual energy supply at sustained transmission of the nervous impulse. However, the high percentage of enlarged organelles found in old rats may witness a morphofunctional compensatory response.
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PMID:Impaired succinic dehydrogenase activity of rat Purkinje cell mitochondria during aging. 959 23

Yeast deficient in the cytosolic copper/zinc superoxide dismutase (SOD1) exhibit metabolic defects indicative of oxidative damage even under non-stress conditions. To help identify the endogenous sources of this oxidative damage, we isolated mutant strains of S. cerevisiae that suppressed metabolic defects associated with loss of SOD1. Six complementation groups were isolated and three of the corresponding genes have been identified. One sod1Delta suppressor represents SSQ1 which encodes a hsp70-type molecular chaperone found in the mitochondria. A second sod1Delta suppressor gene, designated JAC1, represents a new member of the 20-kDa J-protein family of co-chaperones. Jac1p contains a mitochondrial targeting consensus sequence and may serve as the partner for Ssq1p. Homologues of Ssq1p and Jac1p are found in bacteria in close association with genes proposed to be involved in iron-sulfur protein biosynthesis. The third suppressor gene identified was NFS1. Nfs1p is homologous to cysteine desulfurase enzymes that function in iron-sulfur cluster assembly and is also predicted to be mitochondrial. Each of the suppressor mutants identified exhibited diminished rates of respiratory oxygen consumption and was found to have reduced mitochondrial aconitase and succinate dehydrogenase activities. Taken together these results suggest a role for Ssq1p, Jac1p, and Nfs1p in assembly/maturation of mitochondrial iron-sulfur proteins and that one or more of the target Fe/S proteins contribute to oxidative damage in cells lacking copper/zinc SOD.
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PMID:Suppressors of superoxide dismutase (SOD1) deficiency in Saccharomyces cerevisiae. Identification of proteins predicted to mediate iron-sulfur cluster assembly. 981 17

Deficiency of neuronal growth inhibitory factor (GIF) and abnormalities in zinc homeostasis have been suggested to play a role in the neuropathogenesis of Alzheimer's disease. We report here that embryonic chick cerebral cell cultures zinc and copper containing GIF in the presence of marmoset hippocampal extract reduces significantly and concentration dependently mitochondrial succinate dehydrogenase activity (MTT) and cell mass. In contrast, no indications could be found that GIF affected neural retina cell cultures. Our results suggest that the observed effects of GIF are not elicited by zinc.
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PMID:Growth inhibitory factor and zinc affect neural cell cultures in a tissue specific manner. 985 Dec 88

Activated sludge is a rich source of nitrogenous matter and has been recommended as cheap supplement in animal feed. It has been incorporated into cattle and poultry feed. It is well known that sewage of purely domestic origin is also contaminated with heavy metals, pesticides, and other organic pollutants. A study was undertaken to determine the toxic effects of heavy metal-contaminated domestic sewage sludge on young male Wistar rats by supplementing dehydrated activated sludge in their diet at concentrations of 5, 10, 15 and 20%. The sludge was found to be contaminated with 1.820 (zinc), 0.273 (nickel), 0.017 (lead), 0.053 (copper), 0.006 (chromium), and 0.005 (cadmium)mg/g of dry sludge, by analysis by atomic absorption spectroscopy. The toxic effects of sludge-supplemented diets on individual groups of rats were assessed by assaying various enzyme activities in serum, liver, muscle, and brain. Levels of serum and liver alanine aminotransferase and succinate dehydrogenase (SDH) were significantly low in all the sludge-supplemented diet-fed (SSDF) rats. Similarly, serum lactate dehydrogenase (LDH) and muscle SDH activity were also significantly reduced in the SSDF rats. On the other hand, liver and muscle LDH, serum and liver aspartate aminotransferase, and serum and muscle alkaline phosphatase activities were significantly higher in all the SSDF animals. Brain and muscle acetylcholinesterase activity was significantly high in all the SSDF groups. This study indicates that even though the sludge is a rich source of nitrogenous matter, its supplementation in poultry and animals feed should be done with caution. Otherwise, the contaminants found in the sludge will biomagnify in the food chain and lead to various toxicological hazards.
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PMID:A study of toxic effects of heavy metal contaminants from sludge-supplemented diets on male Wistar rats. 1005 66

Cytochrome-c oxidase is the copper-dependent terminal respiratory complex (complex IV) of the mitochondrial electron transport chain whose activity in a variety of tissues is lowered by copper deficiency. Because inhibition of respiratory complexes increases the production of reactive oxygen species by mitochondria, it is possible that copper deficiency increases oxidative stress in mitochondria as a consequence of suppressed cytochrome-c oxidase activity. In this study, the activities of respiratory complex I + III, assayed as NADH:cytochrome-c reductase, complex II + III, assayed as succinate:cytochrome-c reductase, complex IV, assayed as cytochrome-c oxidase, and fumarase were measured in mitochondria from HL-60 cells that were grown for seven passages in serum-free medium that was either unsupplemented or supplemented with 50 n M CuSO4. Fumarase activity was not affected by copper supplementation, but the complex I + III:fumarase and complex IV:fumarase ratios were reduced 30% and 50%, respectively, in mitochondria from cells grown in the absence of supplemental copper. This indicates that copper deprivation suppressed the electron transfer activity of copper-independent complex I + III as well as copper-dependent complex IV. Manganese superoxide dismutase (MnSOD) content was also increased 49% overall in the cells grown in the absence of supplemental copper. Furthermore, protein carbonyl groups, indicative of oxidative modification, were present in 100-kDa and 90-kDa proteins of mitochondria from copper-deprived cells. These findings indicate that in cells grown under conditions of copper deprivation that suppress cytochrome-c oxidase activity, oxidative stress in mitochondria is increased sufficiently to induce MnSOD, potentiate protein oxidation, and possibly cause the oxidative inactivation of complex I.
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PMID:Copper deprivation potentiates oxidative stress in HL-60 cell mitochondria. 1035 26

The authors show that the inhibitor of the succinate dehydrogenase, 3-nitroproprionic acid (3-NPA), which in high doses and with chronic administration is a neurotoxin, can induce profound tolerance to focal cerebral ischemia in the rat when administered in a single dose (20 mg/kg) 3 days before ischemia. Infarcts were approximately 70% and 35% smaller in the 3-NPA preconditioned groups of permanent and transient focal cerebral ischemia, respectively. This regimen of 3-NPA preconditioning neither induced necrosis, apoptosis, or any other histologically detectable damage to the brain, nor did it affect behavior of the animals. 3-NPA led to an immediate (1-hour) and long-lasting (3-day) decrease in succinate dehydrogenase activity (30% reduction) throughout the brain, whereas only a short metabolic impairment occurred (ATP decrease of 35% within 30 minutes, recovery within 2 hours). The authors found that 3-NPA induces a burst of reactive oxygen species and the free radical scavenger dimethylthiourea, when administered shortly before the 3-NPA stimulus, completely blocked preconditioning. Inhibition of protein synthesis with cycloheximide given at the time of 3-NPA administration completely inhibited preconditioning. The authors were unsuccessful in showing upregulation of mRNA for the manganese superoxide dismutase, and did not detect increased activities of the copper-zinc and manganese superoxide dismutases, prototypical oxygen free radicals scavenging enzymes, after 3-NPA preconditioning. The authors conclude that it is possible to pharmacologically precondition the brain against focal cerebral ischemia, a strategy that may in principal have clinical relevance. The data show the relevance of protein synthesis for tolerance, and suggests that oxygen free radicals may be critical signals in preconditioning.
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PMID:Respiratory chain inhibition induces tolerance to focal cerebral ischemia. 1056 69

The antioxidant propyl gallate (PG) induced lipid peroxidation in combination with non-toxic Cu(II) concentrations in human fibroblasts. This was measured by the thiobarbituric acid assay (TBA assay) and by detection of accumulating fluorescent products after a 1-h treatment of cells with CuCl2/PG at concentrations higher than 0.125 mM. PG alone led to a significant reduction of thiobarbituric acid-reactive substances (TBARS) demonstrating its antioxidative properties. Time course studies of lipid peroxidation by PG/Cu(II) showed that formation of TBARS was preceded by a lag phase of 60 min. Thereafter, the TBARS value increased rapidly for 1 h and then reached a constant maximum or slightly decreased. The induction of lipid peroxidation by PG/Cu(II) is probably due to the formation of reactive species like reactive oxygen species (ROS), Cu(I) and semiquinone radicals which are able to participate in initiation and propagation of lipid peroxidation. Combination effects of PG/Cu(II) were demonstrated also on inhibition of membrane-bound succinate dehydrogenase. Cytosolic esterases were affected only slightly. The greater susceptibility of membrane-bound enzymes is in accordance with the lipid peroxidation-inducing effects of PG/Cu(II).
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PMID:Induction of lipid peroxidation in human fibroblasts by the antioxidant propyl gallate in combination with copper(II). 1059 27

Chlamydomonas reinhardtii adapts to copper deficiency by degrading apoplastocyanin and inducing Cyc6 and Cpx1 encoding cytochrome c(6) and coproporphyrinogen oxidase, respectively. To identify other components in this pathway, colonies resulting from insertional mutagenesis were screened for copper- conditional phenotypes. Twelve crd (copper response defect) strains were identified. In copper-deficient conditions, the crd strains fail to accumulate photosystem I and light-harvesting complex I, and they contain reduced amounts of light-harvesting complex II. Cyc6, Cpx1 expression and plastocyanin accumulation remain copper responsive. The crd phenotype is rescued by a similar amount of copper as is required for repression of Cyc6 and Cpx1 and for maintenance of plastocyanin at its usual stoichiometry, suggesting that the affected gene is a target of the same signal transduction pathway. The crd strains represent alleles at a single locus, CRD1, which encodes a 47 kDa, hydrophilic protein with a consensus carboxylate-bridged di-iron binding site. Crd1 homologs are present in the genomes of photosynthetic organisms. In Chlamydomonas, Crd1 expression is activated in copper- or oxygen-deficient cells, and Crd1 function is required for adaptation to these conditions.
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PMID:The Crd1 gene encodes a putative di-iron enzyme required for photosystem I accumulation in copper deficiency and hypoxia in Chlamydomonas reinhardtii. 1081 5

Chlorophyllin (CHL), the sodium-copper salt and the water-soluble analogue of the ubiquitous green pigment chlorophyll, has been attributed to have several beneficial properties. Its antioxidant ability, however, has not been examined in detail. Using rat liver mitochondria as model system and various sources for the generation of reactive oxygen species (ROS) we have examined the membrane-protective properties of CHL both under in vitro and ex vivo conditions. Oxidative damage to proteins was assessed as inactivation of the enzymes, cytochrome c oxidase and succinic dehydrogenase besides formation of protein carbonyls. Damage to membrane lipids was measured by formation of lipid hydroperoxides and thiobarbituric acid reactive substances. The effect of this compound on the antioxidant defense system was studied by estimating the level of glutathione and superoxide dismutase. ROS were generated by gamma-radiation, photosensitization, ascorbate-Fe(2+), NADPH-ADP-Fe(3+) and the peroxyl radical generating agent, azobis-amidopropane hydrochloride. Our results show that CHL is highly effective in protecting mitochondria, even at a low concentration of 10 microM. The antioxidant ability, at equimolar concentration, was more than that observed with ascorbic acid, glutathione, mannitol and tert-butanol. When CHL was fed to mice at a dose of 1% in drinking water, there was a significant reduction in the potential for oxidative damage in cell suspensions from liver, brain and testis. To examine the possible mechanisms responsible for the observed antioxidant ability we have studied the reaction of CHL with the potent ROS in the form of hydroxyl radical and singlet oxygen. The compound shows a fairly high rate constant with singlet oxygen, in the order of 1.3x10(8) M(-1) s(-1). In conclusion, our studies showed that CHL is a highly effective antioxidant, capable of protecting mitochondria against oxidative damage induced by various ROS.
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PMID:Chlorophyllin as an effective antioxidant against membrane damage in vitro and ex vivo. 1101 64


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