Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total and mitochondrial glycerolphosphate acyltransferase activities were measured after 24 hr exposure of rat hepatocytes to Adriamycin. Both activities decreased with increasing concentrations of Adriamycin. The activity of the microsomal glycerolphosphate acyltransferase, which was determined from the difference between the total and mitochondrial enzyme activity, also decreased with increasing drug concentration. The effect on glycerolphosphate acyltransferase was specific as there was no change in lactate dehydrogenase or cytochrome oxidase activity in this time period. Adriamycin did not inhibit mitochondrial glycerolphosphate acyltransferase activity in vitro. After 24 hr exposure of hepatocytes to Adriamycin no change was observed in the biosynthesis of phosphatidylcholine or triacylglycerol. Secretion of lipid into the medium was measured over the subsequent 24 hr. There was a significant reduction in very low density lipoprotein secretion as measured by triacylglycerol secretion from cells incubated with 5 microM Adriamycin. Cells were damaged by the 48 hr exposure to 1 microM and higher concentrations of Adriamycin as evidenced by a fall in lactate dehydrogenase activity in these cells. The secretion of lysophosphatidylcholine, as measured by the incorporation of [3H]glycerol into medium lysophosphatidylcholine, was significantly increased when cells were incubated with 5 microM Adriamycin. The results are discussed in relation to the effect of Adriamycin on hepatic lipid metabolism and the cardiotoxicity of the drug.
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PMID:The effect of adriamycin on glycerolphosphate acyltransferase and lipid metabolism in rat hepatocytes in monolayer culture. 222 13

The stoichiometry and dissociation constant for the binding of homogeneous chicken heart mitochondrial creatine kinase (MiMi-CK) to mitoplasts was examined under a variety of conditions. Salts and substrates release MiMi-CK from mitoplasts in a manner that suggests an ionic interaction. The binding of MiMi-CK to mitoplasts is competitively inhibited by Adriamycin, suggesting that they compete for the same binding site. Fluorescence measurements also show that Adriamycin binds to MiMi-CK so that the effect of Adriamycin on the binding of MiMi-CK to mitoplasts is not simple. Titrating mitoplasts with homogeneous MiMi-CK at different pH values shows a pH-dependent equilibrium involving a group(s) on either the membrane or the enzyme with a pKa = 6. Extrapolating these titrations to infinite MiMi-CK concentration gives 14.6 IU bound/nmol cytochrome aa3 corresponding to 1.12 mol MiMi-CK/mol cytochrome aa3. Chicken heart mitochondria contain, after isolation, 2.86 +/- 0.42 IU/nmol cytochrome aa3. Titrating respiring mitoplasts with carboxyatractyloside gives at saturation 3.3 mol ADP/ATP translocase/mol cytochrome aa3. Therefore, chicken heart mitoplasts can maximally bind about 1 mol of MiMi-CK per 3 mol translocase; in normal chicken heart mitochondria about 1 mol of MiMi-CK is present per 13 mol translocase.
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PMID:Association of chicken mitochondrial creatine kinase with the inner mitochondrial membrane. 381 58

We have investigated the effect of doxorubicin (Adriamycin) on the yeast Saccharomyces cerevisiae. Drug treatment was found to be cytotoxic to wild-type strains, in a concentration-dependent manner, whereas a petite mutant lacking the cytochrome oxidase (EC 1.9.3.1) subunit IV gene was resistant to doxorubicin. Transformation of the doxorubicin-resistant mutant with a yeast in vivo expression vector harboring the cytochrome oxidase subunit IV gene restored both respiration and sensitivity to doxorubicin. Another petite strain, with a mutation in the mitochondrial adenine nucleotide translocator (pet9), did not display doxorubicin resistance. However, in contrast to the subunit IV mutant, it possesses a functional respiratory chain. We also compared the cytotoxic effect of doxorubicin with those of daunorubicin and mitoxantrone in yeast. We found comparable levels of cytotoxicity for doxorubicin and daunorubicin, which were significantly greater than that for mitoxantrone. Finally, we constructed a yeast strain that overexpresses manganese superoxide dismutase (EC 1.15.1.1), an antioxidant enzyme present in mitochondria. Overexpression of manganese superoxide dismutase protected significantly against doxorubicin and daunorubicin cytotoxicity but only slightly against mitoxantrone cytotoxicity. Collectively, our results provide direct in vivo evidence that superoxide radicals participate in doxorubicin- and daunorubicin-induced cytotoxicity in yeast. Furthermore, these results indicate that mitochondrial respiration is a crucial factor in anthracycline, and perhaps mitoxantrone, cytotoxicity in yeast.
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PMID:Doxorubicin, daunorubicin, and mitoxantrone cytotoxicity in yeast. 780 47

The effect of the combination of Adriamycin (ADM) with rhein (RH), an anti-inflammatory drug, on the electron flow through site III and IV of the respiratory chain of rat liver mitochondria was investigated. RH, even at high concentrations, does not inhibit either duroquinol (DHQ) oxidation or cytochrome oxidase activity both of which are decreased by ADM in a dose-dependent manner. The analysis of interaction, performed with the isobolar method, shows a strong synergistic effect that cannot be ascribed to increased permeability of the mitochondrial membranes brought about by RH. The mechanism by which RH potentiates the effect of ADM on DHQ oxidation and cytochrome oxidase activity is most likely to be changes induced in the physical status of the inner mitochondrial membrane such as to permit low ADM concentrations to bind and segregate enough cardiolipin to inhibit electron transport through complex III and IV.
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PMID:Rhein enhances the effect of adriamycin on mitochondrial respiration by increasing antibiotic-membrane interaction. 820 95

Adriamycin (ADR), a well-known antitumoral drug, interacts with DNA (nuclear and mitochondrial) and cardiolipin. Moreover, ADR induces numerous mitochondrial modifications in sensitive cells. However, no results have yet been obtained as to the repercussions of drug effects on oxido-reductase activities in ADR-resistant cells. To analyze mitochondrial damage induced by ADR treatment, we investigated lactate content, oxygen consumption, respiratory chain activities, and cytochrome content in ADR-sensitive K562 cells and two ADR-resistant variants (K562/R0.2 and K562/R0.5 cells). Biochemical investigations in ADR-resistant cells showed several mitochondrial modifications (in comparison to the parental cell line) according to the variant line and the physiologic state. More particularly, in K562/R0.5 cells cytochrome c (cyt c) oxidase (COX; EC 1.9.3.1) activity and cytochrome aa3 content dramatically decreased since cells enter into the stationary phase. Regardless of the number of multidrug-resistant cell subcultures in ADR-free medium, the cytochrome c oxidase activity in the stationary phase remained unchanged, indicating an irreversible effect of the drug. These alterations could correspond to several modifications of the nuclear and/or mitochondrial genome(s) following acquisition of the ADR resistance phenotype by K562 cells.
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PMID:Modifications of oxido-reductase activities in adriamycin-resistant leukaemia K562 cells. 976 20