Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male, Balb/c mice were fed diets containing dieldrin (10 ppm) and DDT (100-175 ppm) for 75 weeks. Control and treated mice were serially killed and their livers analyzed by histological and histochemical procedures after 2, 4, 8, 16, 36, 52 and 75 weeks of exposure. Mice administered both chlorinated hydrocarbons initially responded with centrolobular hepatocytomegaly. The cells were characterized by decreased glucose-6-phosphatase and succinate dehydrogenase activity. At later periods 52 through 75 weeks, foci of phenotypically-altered hepatocytes were noted. The cells of these lesions were basophilic or clear-staining in hematoxylin and eosin-stained sections and displayed increased gamma glutamyl transpeptidase activity. In mice preloaded with iron dextran, cells of foci were negative for iron when the surrounding parenchyma was siderotic. Hepatocellular adenomas (HA) and carcinomas (HPC) were composed of cells with increased gamma glutamyl transpeptidase and glucose-6-phosphate dehydrogenase and decreased glucose-6-phosphatase and succinate dehydrogenase activity. In iron loaded mice, the cells of HA and HPC did not stain for iron in otherwise siderotic surroundings. Both hepatocellular foci and adenomas may be potential precursors of mouse hepatocellular carcinomas.
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PMID:Histogenesis of dieldrin and DDT-induced hepatocellular carcinoma in Balb/c mice. 256 34

The effects of DDT on the energy-related functions of rat-liver mitochondria were examined. ADP-stimulated respiration was much more sensitive to inhibition by DDT than was uncoupler-stimulated respiration when succinate or ascorbate/TMPD was used as the substrate. Ca2+ uptake driven by ATP hydrolysis was inhibited by DDT. These results indicate that DDT inhibits ATPase itself. In addition, DDT blocked succinate dehydrogenase and the cytochrome b-c span of the electron transport chain, which also secondarily reduced ATP synthesis. The uncoupling action due to DDT was only seen at high concentrations with ascorbate/TMPD as the substrate. However, this action was masked because of the increased inhibition of the electron transport chain when the substrate was changed to succinate.
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PMID:Effects of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) on ATPase-linked functions in isolated rat-liver mitochondria. 315 37

The effects of DDE (2,2-bis(p-chlorophenyl)-1,1-dichloroethylene), the major metabolite of DDT (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane), on rat liver mitochondrial bioenergetic activities were examined. The approach developed by M. D. Brand (Biochim Biophys Acta 1018: 128-133, 1990) was used to assess the effects of DDE because it is possible to discriminate the sites of action of compounds having pleiotypic effects on oxidative phosphorylation. Data were further confirmed using a "classical" approach, including measurements of transmembrane potential, respiratory indexes, enzymatic activities and membrane permeability to protons. DDE up to 40 nmol/mg protein affected the proton motive force generating system. In fact, DDE interacted with succinate dehydrogenase (complex II), decreasing respiration and membrane potential. In this concentration range, the permeability of the inner membrane to protons remained intact. Only higher concentrations (> or = 80 nmol/mg) increased permeability to protons, uncoupling oxidation from phosphorylation. The phosphorylative system was not affected because the rate of ATP synthesis was unchanged. In addition, data from carbonyl cyanide m-chlorophenylhydrazone-uncoupled rotenone-inhibited preparations or submitochondrial particles indicated that F0F1 ATPase activity is not affected by DDE. Therefore, DDE inhibition of complex II and putative inhibition of succinate translocation explain the depression of mitochondrial respiration. The use of appropriate substrates and assay conditions indicates that complexes I, III and IV were not affected by DDE. The uncoupling of oxidative phosphorylation at high concentrations (> 80 nmol DDE/mg protein) was probably related to deleterious effects on the integrity of the mitochondrial membrane. We confirmed that the technique originally proposed by Brand is useful for characterizing the effects of xenobiotics on oxidative phosphorylation. In addition, data provided by this technique closely agree with data from classical studies.
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PMID:Interactions of 2,2-bis(p-chlorophenyl)-1,1-dichloroethylene with mitochondrial oxidative phosphorylation. 906 33