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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It had previously been held that chlorate is not itself toxic, but is rendered toxic as a result of nitrate reductase-catalysed conversion to chlorite. This however cannot be the explanation of chlorate toxicity in Aspergillus nidulans, even though nitrate reductase is known to have chlorate reductase activity. Among other evidence against the classical theory for the mechanism of chlorate toxicity, is the finding that not all mutants lacking nitrate reductase are clorate resistant. Both chlorate-sensitive and resistant mutants lacking nitrate reductase, also lack chlorate reductase. Data is presented which implicates not only nitrate reductase but also the product of the nirA gene, a positive regulator gene for nitrate assimilation, in the mediation of chlorate toxicity. Alternative mechanisms for chlorate toxicity are considered. It is unlikely that chlorate toxicity results from the involvement of nitrate reductase and the nirA gene product in the regulation either of nitrite reductase, or of the pentose phosphate pathway. Although low pH has an effect similar to chlorate, chorate is not likely to be toxic because it lowers the pH; low pH and chlorate may instead have similar effects. A possible explanation for chlorate toxicity is that it mimics nitrate in mediating, via nitrate reductase and the nirA gene product, a shut-down of nitrogen catabolism. As chlorate cannot act as a nitrogen source, nitrogen starvation ensues.
Mol Gen Genet 1976 Jul 23
PMID:Chlorate toxicity in Aspergillus nidulans. Studies of mutants altered in nitrate assimilation. 0 97

The lower Vmax of 6PGDH with respect to G6PDH and its higher sensitivity to inhibition by NADPH, suggest the existence of an imbalance between the two dehydrogenases of the pentose phosphate pathway in rat liver. Possible modulators of these activities, particularly in relation with the inhibition by NADPH in physiological conditions, have been investigated. The results suggest that in both cases the inhibition by NADPH is strictly isosteric and that the relative affinities for the reduced and oxidized forms of the pyridine nucleotide are unaffected by glutathion, the intermediates of the pentose phosphate shunt or some divalent ions.
Mol Cell Biochem 1977 Oct 07
PMID:Effectors of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. 2 33

Thyroid hormones regulate lipid metabolism by affecting lipogenesis as well as lipolysis. The present paper discusses the way thyroidectomy induced an enhancement in lipogenesis in rat fat cells. The doubling in the conversion of glucose to CO2 and fatty acids seen after thyroidectomy was found to be due to a modification in the actual pathway of glucose metabolism: there was a preferential stimulation of the conversion of glucose to CO2 by the pentose cycle (utilisation of [1-14C]glucose) while the production of fatty acids and glyceride-glycerol proceeded, respectively, much more, or only slightly more, via the pathway of [6-14C]glucose metabolism. Studies employing the phosphodiesterase inhibitor MIX, or the cyclic AMP analogue, DBcAMP showed that the lipogenic process depends on cyclic AMP. As the stimulatory effect of thyroidectomy was not abolished, however, lipogenesis must be under the independent control of both cyclic AMP and absence of thyroid hormones. Insulin, a further mediator of lipogenesis was found to further enhance the already preexisting high conversion of glucose to CO2 in fat cells from thyroidectomized rats. It is concluded that at least three factors modify lipogenesis: thyroidectomy, cyclic AMP and insulin; each achieving its effect in an independent manner.
Mol Cell Endocrinol 1979 Jun
PMID:Cyclic AMP and lipogenesis in fat cells from thyroidectomized rats. 8 52

1. Hypoxanthine--guanine phosphoribosyltransferase (HGPRT) activity was measured in erythrocyte haemolysates and quadriceps muscle extracts of normal and dystrophic 129 ReJ and C57 BL/6J mice with [8(-14)C]hypoxanthine as substrate and 5-phosphorylribose 1-pyrophosphate as a ribose 5-phosphate donor. [8(-14)C]Inosine monophosphate formed was separated by high-voltage electrophoresis and radioactivity was measured by liquid-scintillation counting. 2. In erythrocyte haemolysates, HGPRT activity was similar in normal and dystrophic C57 BL/6J mice but was significantly higher in dystrophic than in normal 129 ReJ mice. Elevated enzyme activity was observed only in mice that were clinically severely affected. 3. In muscle homogenates, HGPRT activity was significantly higher in dystrophic than in normal animals of both 129 ReJ and C57 BL/6J mice. Enzyme activity was not related to the severity of the disease. 4. It is suggested that changes in erythrocytes are secondary to the dystrophic process and that elevated HGPRT activity in skeletal muscle may be related to abnormal energy metabolism, possibly via the pentose monophosphate shunt.
Clin Sci Mol Med Suppl 1978 Dec
PMID:Hypoxanthine--guanine phosphoribosyltransferase activity in blood and skeletal muscles of normal and dystrophic mice. 28 49

Mutants of Klebsiella aerogenes W70 that metabolize the uncommon pentose D-arabinose were isolated. These mutants were found to be either constitutive or indicible by D-arabinose for the synthesis of enzymes in the L-fucose pathway. Such mutants could then utilize L-fucose isomerase to convert the structurally similar D-arabinose molecule to D-ribulose. D-Ribulose is an intermediate and the inducer of an existing ribitol pathway and could thus be metabolized. In those D-arabinose-positive mutants where the ribitol pathway was blocked by mutation, D-ribulose could alternatively be metabolized by using the remaining L-fucose pathway enzymes. When the two D-arabinose catabolic routes were compared, catabolism of D-arabinose via the ribitol pathway was found to be more efficient. Catabolism of D-arabinose using the L-fucose pathway permitted D-ribulose to escape into the media and produced an unmetabolizable end product, L-glycolic acid. A comparison of growth using constitutive versus inducible control of the borrowed L-fucose isomerase did not reveal an advantage for one control type over the other. Several differences were observed, however, when we determined the degree to which these control mutations perturbed the normal functioning of the L-fucose and associated pathways. Growth of the constitutive mutant was impaired with L-fucose as substrate. The inducible-control mutant had altered growth characteristics on ribitol and L-rhamnose.
J Mol Evol 1977 Nov 25
PMID:A comparison of alternate metabolic strategies for the utilization of D-arabinose. 33 26

1. Gliadin from which carbohydrate was removed by treatment with carbohydrase from Aspergillus niger was fed to three coeliac patients in remission. 2. Xylose absorption, mucosal morphology and brush-border enzymes were used to assess the toxicity of the carbohydrase-treated gliadin. 3. Gliadin treated with carbohydrases did not damage the intestinal mucosa of the coeliac patients. 4. The primary structure of the gliadin proteins was not altered by the enzyme treatment.
Clin Sci Mol Med 1977 Jul
PMID:Coeliac disease: the abolition of gliadin toxicity by enzymes from Aspergillus niger. 87 19

The uptake of D-[U-14C]xylose by isolated rat soleus muscle was studied, using D-[1-3H]-sorbitol as an extracellular marker. Xylose uptake was limited by the diffusion of the sugar into and through the extracellular water. This could be overcome in part by allowing the test sugars to pre-equilibrate in the extracellular water at 0 degrees C, before measuring xylose uptake. It was not necessary to fill the extracellular water with the test sugars to obtain maximum rates of xylose uptake. From this it was concluded that the sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugars entering the interstitial water. Pre-equilibration was more effective in the absence of insulin than in the presence of the hormone. This suggested that insulin may influence sugar uptake at some site prior to the cell membrane. Pre-incubation at 0 degrees C itself stimulated sugar transport. This effect of cooling was not influenced by insulin, nor did it appear to affect the stimulatory action of insulin on xylose transport.
Mol Cell Endocrinol 1976 Mar
PMID:Short-term measurement of D-xylose uptake by isolated rat soleus muscle. 126 31

Fat-storing cells (perisinusoidal lipocytes, Ito cells) are the major connective tissue-producing cell type in liver. In areas of necroinflammation the cells proliferate and transform into desmin and smooth muscle alpha-actin-positive myofibroblast-like cells which synthesize a broad spectrum of significant amounts of collagens, proteoglycans, and matrix glycoproteins. Available data suggest a central role for these cells in the pathogenesis of fibrosis. Beta-D-Xyloside, an artificial initiation site for galactose-linked glycosaminoglycans, thereby uncoupling the synthesis of core protein and GAG, was used as a probe to study main cellular functions under conditions of abrogated proteoglycan synthesis. The exposure for 48 hr of fat-storing cells to p-nitrophenyl beta-D-xyloside (PNP-Xyl) increased dose-dependently the synthesis of [35S]sulfate-labeled medium GAG. Maximum stimulation of fivefold above normal was reached at 1.0 mM PNP-Xyl. Higher concentrations of PNP-Xyl progressively decreased the stimulatory effect on GAG synthesis. The relative composition of GAG in medium (60% chondroitin sulfate, 34% dermatan sulfate), at the cell surface, and intracellularly (mainly heparan sulfate) was not changed significantly by PNP-Xyl. The amounts of intracellular and cell surface-bound GAG were reduced by 40 and 30%, respectively, by PNP-Xyl leading to a depletion of heparan sulfate at the cell surface. Pulse-chase experiments revealed that xyloside-initiated GAG were secreted immediately after synthesis into the medium. GAG synthesized in the presence of 1 and 5 mM PNP-Xyl were free of core protein, and the molecular size of the GAG chains was smaller than that of GAG obtained from beta-eliminated proteoglycans synthesized in control cultures. At concentrations above 3 mM PNP-Xyl generated a dose-dependent inhibition of cell proliferation, which was at any stage of culture fully reversible upon removal of the drug. Viability and general protein synthesis were not reduced, but fat-storing cell transformation and deposition of matrix glycoproteins were retarded. Only a very small fraction of drug-treated cells (5 mM PNP-Xyl) did express on the 11th culture day smooth muscle iso-alpha-actin- and desmin-containing cytoskeletal filaments, which are important indicators of transformation into myofibroblast-like cells. Furthermore, the synthesis of hyaluronan and the expression of immunostained fibronectin, laminin, and tenascin were reduced in cultures exposed to 5 mM PNP-Xyl. The described cellular functions were not affected by exposure of fat-storing cells to p-nitrophenyl beta-D-galactoside.(ABSTRACT TRUNCATED AT 400 WORDS)
Exp Mol Pathol 1991 Oct
PMID:Proliferation and transformation of cultured liver fat-storing cells (perisinusoidal lipocytes) under conditions of beta-D-xyloside-induced abrogation of proteoglycan synthesis. 171 76

Cobalt, a metal with numerous industrial applications, has been associated with lung disease, an extreme form of which is an interstitial fibrosis. The biochemical mechanisms underlying this toxicity are not understood. In vitro studies have suggested that cobalt(II) ions are able to generate reactive oxidant species (possibly hydroxyl radical) in a reaction with hydrogen peroxide, and we have hypothesized that the occurrence of such an event in lung tissue, and the subsequent development of oxidative damage, may contribute to this pulmonary toxicity. The intratracheal instillation of CoCl2 into hamster lungs resulted after 3 h in decreased levels of reduced glutathione and increases in levels of oxidized glutathione and in the activity of the pentose phosphate pathway. These changes, which are compatible with the generation of oxidative stress, were reversed by 48 h at low Co2+ doses (1.0 to 1,000 micrograms/kg). Irreversible changes at higher doses coincided with the onset of pulmonary edema. Incubation of lung slices with CoCl2 (0.1 to 10 mM) resulted in time- and Co2+ concentration-dependent increases in levels of oxidized glutathione and protein-mixed disulfides and a decrease in reduced glutathione. A concentration-dependent stimulation of the pentose phosphate pathway was also observed. These changes preceded the detection of overt cell toxicity, as assessed by various biochemical parameters. These data indicate that thiol oxidation constitutes an early event in the pulmonary toxicity of cobalt(II) ions and are compatible with the hypothesis that the generation of oxidative stress may be of significance to the toxic process.
Am J Respir Cell Mol Biol 1991 Aug
PMID:Indices of oxidative stress in hamster lung following exposure to cobalt(II) ions: in vivo and in vitro studies. 189 47

Oxidative stress induced by cumene hydroperoxide was studied in cultured neonatal rat myocytes. A progressive increase of irreversible cell injury as determined by leakage of the cytoplastic enzyme alpha-hydroxybutyrate dehydrogenase (alpha-HBDH) from the cells was noted at concentrations ranging from 25-100 microM cumene hydroperoxide (incubation time 90 min). Cumene hydroperoxide-induced damage was reduced or prevented by several compounds: the application of Trolox C, a water-soluble vitamin E analogue, and of phospholipase A2 inhibitors chlorpromazine and (to a lesser extent) quinacrine prevented alpha-HBDH release. ICRF-159, a chelator of divalent cations, ascorbic acid, a potent antioxidant, and the cysteine protease inhibitor leupeptin did not reduce the cumene hydroperoxide-induced cytotoxicity. Detoxification of hydroperoxides by the glutathione peroxidase system results in an increased flux through the pentose phosphate shunt and loss of NADPH. Glucose inhibited the cumene hydroperoxide-induced alpha-HBDH release, probably by replenishing NADPH. These results indicate that cumene hydroperoxide, after exhaustion of the glutathione system, induces irreversible injury in cultured myocytes by a mechanism that depends to a large extent on deterioration of cellular membranes caused by lipid peroxidation and phospholipase activation.
J Mol Cell Cardiol 1990 Oct
PMID:Prevention of cumene hydroperoxide induced oxidative stress in cultured neonatal rat myocytes by scavengers and enzyme inhibitors. 209 37


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