Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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In a previous study the authors demonstrated monotypic foci, all of timidus type, in the atherosclerotic lesions and normal aortic tissue of glucose-6-phosphate dehydrogenase (G-6-PD) mosaic hares fed 25-hydroxycholesterol or triol in addition to a high-cholesterol diet. Other hares fed the high-cholesterol diet without the cholesterol oxidation product additives did not develop monotypic foci. In the current study the question asked was whether ditypic samples from lesions or aortic mediae of the same hares fed the additives would show a higher percentage of timidus type G-6-PD than the hares fed the cholesterol alone. The results showed a significantly higher percentage of timidus type in both lesions and mediae in the groups fed either 25-hydroxycholesterol or triol than in the group fed cholesterol alone. The observations suggest that the change from ditypism to monotypism reported earlier with these cholesterol oxidation products was the result of progressive elimination of the europaeus type to leave only the timidus G-6-PD. This is consistent with the "selective advantage of one phenotype over the other" hypothesis for explaining the observed monotypism as opposed to the "genetic transformation" hypothesis.
Exp Mol Pathol 1985 Feb
PMID:Mosaicism in female hybrid hares heterozygous for glucose-6-phosphate dehydrogenase. VII. Evidence for selective advantage of one phenotype over the other in ditypic samples from aortas of hares fed cholesterol oxidation products. 396 50

The possibility that myocardial ischaemia alters the defence mechanisms against oxygen toxicity has been investigated. Ischaemia was induced in isolated, perfused rabbit hearts by reducing coronary flow from 25 ml/min to 1 ml/min for 90 min. Two different degrees of ischaemic damage have been achieved using either spontaneously beating or electrically stimulated hearts. The effects of post-ischaemic reperfusion were also followed for 30 min. Tissue activity of superoxide dismutase (SOD), glutathione peroxidase and reductase (GPD and GRD) have been determined together with tissue content of reduced and oxidized glutathione (GSH and GSSG) and of protein SH groups. The changes in myocardial ATP and CP content and release of CPK and of GSH and GSSG were also determined. Systolic and diastolic pressures were continuously monitored. In the spontaneously beating hearts ischaemia induced a reduction of tissue GSH and protein SH groups. On reperfusion there was a recovery of mechanical function, a transient release of GSH into the coronary effluent and an increase of tissue GSH. In the paced hearts, ischaemia resulted in 50% reduction of mitochondrial SOD activity together with a reduction of tissue GSH and protein SH groups. Reperfusion induced a massive release of CPK and of GSH and GSSG, a further reduction of tissue GSH concomitant with an increase of GSSG and no recovery of mechanical function. GPD and GRD activity were not affected by ischaemia and reperfusion. These data indicate that severe ischaemia induces a reduction of the protective mechanisms against oxygen toxicity.
J Mol Cell Cardiol 1985 Oct
PMID:Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity. 406 39

The effects of FSH on the aromatase activity of rat granulosa cells in culture were studied by measuring the stereospecific transfer of 3H from [1,2,6,7-3H]testosterone or [1 beta-3H]testosterone into 3H2O. The use of 3H2O release as a specific assay for aromatization in granulosa cells was validated by various means. 2 days after plating, cultures of granulosa cells released only minimal amounts of 3H2O from [1 beta-3H]testosterone during a 3-h incubation, whereas cells which had been treated with FSH, or with (Bu)2cAMP plus 3-isobutyl-1-methylxanthine (MIX), from the time of plating released considerable amounts of 3H2O into the culture medium. The release of 3H2O from [1 beta-3H]testosterone by cultured cells was inhibited by the aromatizable androgens, 19-hydroxytestosterone and 19-hydroxyandrostenedione, indicating the specificity of the method for aromatization. In order to study the mechanism by which FSH enhanced the release of 3H2O, optimal conditions for aromatization by cell-free sonicates were determined. Optimal aromatase activity was achieved by incubating cell-free sonicates at 37 degrees C in the presence of O2 in 20 mM phosphate buffer (pH 7.4) containing 5 mM dithiothreitol, 20 mM MgCl2, 0.5 mM NADP+, 20 mM glucose 6-phosphate and 2 U/ml glucose-6-phosphate dehydrogenase. A concentration of 0.25 microM testosterone and 0.1 microCi tritium was used in the standard assay. Under these conditions the assay was linear for 1 h with up to 150 microgram protein from granulosa cells having maximal aromatase activity. When cells in culture were stimulated with purified FSH for 48 h from the time of plating, the aromatase activity in cell-free sonicates increased in a dose-dependent fashion. The ED50 for Sairam's FSH S-1528 C2 was 12 ng/ml. It was concluded from these studies that FSH increases estrogen levels primarily by inducing an active aromatase rather than by influencing secretion or availability of substrate or cofactor for the aromatization reaction.
Mol Cell Endocrinol 1981 May
PMID:FSH induction of aromatase in cultured rat granulosa cells measured by a radiometric assay. 616 36

Leishmania mexicana mexicana amastigotes have been shown to contain greater activities than promastigotes of the enzymes that catalyse the beta-oxidation of fatty acids, but lower activities of several glycolytic enzymes, with the activity of pyruvate kinase being especially low. The results suggest the beta-oxidation of fatty acids is relatively more important to Leishmania amastigotes than promastigotes, whereas the reverse is true for glycolysis. Succinic dehydrogenase and peptidase activities were much higher in promastigotes than amastigotes. The activities of glucose-6-phosphatase, fructose-1,6-bisphosphatase, acid phosphatase and glucose-6-phosphate dehydrogenase varied less, although in each case the activity was significantly lower in the mammalian stage. A method for lysing and fractionating L. m. mexicana promastigotes has been developed. Using this procedure it has been established that many of the glycolytic and functionally related enzymes are located in cell organelles, that hexokinase is intimately connected with the particulate part of the parasite, and that the microsomal fraction of L. m. mexicana is very different in composition from the microsomes of mammalian liver cells.
Mol Biochem Parasitol 1982 Mar
PMID:A comparative study of Leishmania mexicana amastigotes and promastigotes. Enzyme activities and subcellular locations. 621 17

Six naturally occurring alleles representing four electromorphs of the enzyme glucose-6-phosphate dehydrogenase were transferred by P1-mediated transduction from natural isolates of Escherichia coli into the genetic background of E. coli K12 and were studied in pairwise competition in chemostats limited for glucose in order to estimate differences in growth rate associated with the alleles. Although the level of resolution of such experiments is a growth rate differential of approximately 0.002 h-1, no significant differences among the strains were found. Studies of apparent Km and Vmax in crude enzyme extracts of the strains also failed to reveal any significant differences among the electromorphs. These results support the view that the alleles are selectively neutral or nearly neutral under these conditions.
Mol Biol Evol 1984 Feb
PMID:Selective neutrality of glucose-6-phosphate dehydrogenase allozymes in Escherichia coli. 640 Jun 49

Distribution of glucose-6-phosphate dehydrogenase (G6PD) and 6-phospho-gluconate dehydrogenase (6PGD) in imaginal discs of Drosophila melanogaster was determined. Differential patterns of staining were found in all discs examined, i.e., eye-antennal, wing, leg, labial and genital. By using null mutants for either G6PD or 6PGD, the enzymes were shown to have the same distribution patterns. Staining with glucose-6-phosphate as a substrate resulted in the detection of both G6PD and 6PGD. Results of staining discs from homoeotic mutants indicate that the enzyme distribution patterns are under genetic control. In the presence of the homoeotic engrailed (en) mutation which transforms posterior wing compartment into anterior, the G6PD pattern of the posterior compartment of the wing disc was specifically transformed toward that of the anterior compartment. The bithorax series of homoeotic mutants was similarly investigated. The bithorax (bx3) mutation transforms the anterior part of the haltere to anterior wing blade. Similarly the G6PD pattern in the anterior haltere disc transforms to that of anterior wing disc. The complimentary transformation, postbithorax (pbx) results in a change of the posterior part of the haltere to posterior wing, which is likewise reflected in an altered staining pattern for G6PD in the posterior portion of the haltere disc. The combination of the bx3 and pbx resulted in a staining pattern of the haltere disc virtually indistinguishable from the normal wing disc.
Mol Gen Genet 1983
PMID:Enzyme patterns in D. melanogaster imaginal discs: distribution of glucose-6-phosphate and 6-phosphogluconate dehydrogenase. 641 22

The high basal glucose utilization through hexose monophosphate shunt found in our experimental conditions were almost completely inhibited by oleate, octanoate and caproate. However, the inhibition of glucose oxidation due to butyrate was about 50% whereas ketone bodies and acetate did not inhibit. The rate of triacylglycerol formation was not significantly modified with the above organic acids except oleate that presented a 5-fold increase on labeling incorporation into lipids. Oleate inhibition of glucose oxidation was completely prevented by the NADPH oxidant menadione. There was no inhibition by octanoate, caproate, butyrate or ketone bodies of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase or malic enzyme in adipose tissue homogenates. In contrast, specifically glucose-6-phosphate dehydrogenase was inhibited by oleoyl-CoA. The oleoyl-CoA inhibition was prevented by enzyme preincubation with low NADP concentration. The data lend further support for the hypothesis that fatty acids and NADP fulfill an important role in the modulation of the hexose monophosphate shunt activity.
Mol Cell Biochem 1984 Sep
PMID:Fatty acyl-CoAs as feedback regulators of hexose monophosphate shunt in rat adipocytes. 643 83

It is generally accepted that in psoriasis there is an alteration of epidermal cell proliferation. It has been reported that an increased rate of thymidine incorporation into keratinocytes is found in the upper part of the hair follicle in involved skin, but this is not the case in the lower part. Here we show that cells from psoriatic hair follicles could be brought in culture under the same conditions as those of normal hair follicles. Cells, whether originating from the upper or lower part of the hair follicle sheath either from involved or uninvolved psoriatic skin, show a faster rate of outgrowth in the first days of culture. Moreover, a large number of psoriatic cells have an increased motility in the early stages of culture, as compared to control cells. These properties can no longer be observed after several days in culture. The activity of glucose-6-phosphate dehydrogenase known to be increased in psoriatic plaques is normal in hair follicles isolated from these plaques. Protein gel electrophoretic investigations showed that there is no difference in gel patterns between normal and psoriatic hair follicles. In conclusion, the isolation of human hair follicles represents a simple method that allows psoriatic keratinocytes to be brought in culture and permits the study of certain aspects of the disease.
Mol Biol Rep 1984 Jul
PMID:Psoriatic hair follicle cells. I. Biochemistry and behavior in culture. 647 58

Several thyroid hormone analogs have been tested for thyromimetic activity on rat brain and liver subcellular organelles. The compounds were administered immediately after thyroidectomy to 90 g male S-D rats for 10 days, by daily s.c. injection. In cerebral cortex and liver we measured the activities of mitochondrial succinate cytochrome c reductase and alpha-GPD, and nuclear RNA polymerase I. Brain mitochondrial enzymes were unchanged in thyroidectomized (Tx) and in Tx-treated rats, whereas the activities of these enzymes in liver mitochondria were partially restored by the treatments. RNA polymerase I activity in brain and liver dropped significantly 10 days after thyroidectomy and daily injection of thyroid hormones or analogs maintained the nuclear activity at a normal level. Correlation between the structure of thyroid hormone analogs and their subcellular effects is in good agreement with previous binding and in vivo studies. Enzyme activities stimulated by T3 were lowered by replacing the T3 side-chain by an acetic acid group or by substituting the bridged oxygen atom by atom by CO. In contrast, the activity was enhanced by substituting iodine with a 3' isopropyl group. Although less active than iodine, the 3,5-dimethyl substituents may be introduced without a complete loss of nuclear activity.
Mol Cell Endocrinol 1984 Sep
PMID:Comparative effects of thyroid hormone analogs on the activities of brain and liver mitochondria and nuclei in thyroidectomized rats. 648 4

The normal aortic tissue of black women heterozygous for glucose-6-phosphate dehydrogenase (G-6-PD) usually consists of two cell phenotypes (mosaicism). By electrophoresis two G-6-PD types are demonstrated (ditypism). Advanced atherosclerotic lesions from such women not infrequently yield samples displaying only one G-6-PD type (monotypism). Possible causes for the monotypism include (1) monoclonal origin of the lesion and (2) selective growth and/or survival advantage of one phenotype over the other. We have been attempting to produce monotypism in the aortas of a hybrid hare model that displays G-6-PD mosaicism in the normal state. In the current study 14 G-6-PD mosaic hares were fed a high-cholesterol diet for 6 to 17 months. All developed extensive moderately severe (as compared to humans) atherosclerotic lesions. No monotypic samples were found. Ten hares were fed (in addition to the standard high-cholesterol diet) small doses of one of two cholesterol oxidation products (25-hydroxycholesterol or triol) for 6 to 21 months. Four of the ten developed monotypic foci in either atherosclerotic lesions or normal aortic tissue or both. The reason for giving the oxidation products was because they are cytotoxic for cells in vitro and one (25-hydroxycholesterol) had been shown to be more toxic for one phenotype than the other with cultured fibroblasts from the mosaic hares (not infrequently resulting in the culture becoming monotypic). We suggest that the monotypism observed in vivo was probably produced by a mechanism similar to that operating in vitro.
Exp Mol Pathol 1984 Dec
PMID:Mosaicism in female hybrid hares heterozygous for glucose-6-phosphate dehydrogenase. VI. Production of monotypism in the aortas of 4 of 10 mosaic hares fed cholesterol oxidation products. 651 May 9


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