Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the presence of glucose (2 mg/ml), leucine (10 mM) noticeably increased islets' NADPH contents as well as the NADPH:NADP ratio; the changes occurred as soon as 1 min after its addition. NADH concentrations were also increased by leucine. The NADPH:NADP ratio as well as insulin release stimulated by glucose plus leucine were markedly decreased by methylene blue. The thiol oxidants diamide and tert-butyl hydroperoxide also inhibited insulin secretion in response to glucose plus leucine. Employing the perfused pancreas technique, the insulin-releasing action of p-chloromercuribenzoate was further enhanced by leucine. The combined effects were inhibited by tert-butyl hydroperoxide, however. Our data suggest that the insulin-releasing action of leucine depends on the islets' NADPH and reduced glutathione (GSH); in addition, leucine may contribute to insulin secretion by increasing the islet NADPH:NADP ratio and the NADH:NAD ratio. From the data, we assume that the observed increase of NADPH may lead via GSH to an increase in the number of such thiol groups in the beta-cell membrane, which are believed to be related to stimulation of insulin release and, thus, to increase the sensitivity of the beta-cell to stimulation by glucose and/or leucine.
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PMID:Effect of leucine on the pyridine nucleotide contents of islets and on the insulin released--interactions in vitro with methylene blue, thiol oxidants, and p-chloromercuribenzoate. 3 18

Oxidation of methanol, formaldehyde and formic acid was studied in cells and cell-free extract of the yeast Candida boidinii No. 11Bh. Methanol oxidase, an enzyme oxidizing methanol to formaldehyde, was formed inducibly after the addition of methanol to yeast cells. The oxidation of methanol by cell-free extract was dependent on the presence of oxygen and independent of any addition of nicotine-amide nucleotides. Temperature optimum for the oxidation of methanol to formaldehyde was 35 degrees C, pH optimum was 8.5. The Km for methanol was 0.8mM. The cell-free extract exhibited a broad substrate specificity towards primary alcohols (C1--C6). The activity of methanol oxidase was not inhibited by 1mM KCN, EDTA or monoiodoacetic acid. The strongest inhibitory action was exerted by p-chloromercuribenzoate. Both the cells and the cell-free extract contained catalase which participated in the oxidation of methanol to formaldehyde; the enzyme was constitutively formed by the yeast. The pH optimum for the degradation of H2O2 was in the same range as the optimum for methanol oxidation, viz. at 8.5. Catalase was more resistant to high pH than methanol oxidase. The cell-free extract contained also GSH-dependent NAD-formaldehyde dehydrogenase with Km = 0.29mM and NAD-formate dehydrogenase with Km = 55mM.
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PMID:Studies on methanol - oxidizing yeast. III. Enzyme. 24 Jul 64

The influence of sodium nitroprusside (SNP) on mitochondrial respiration was examined in rat liver mitochondria. The addition of SNP 1 mmol litre-1 during state 3 respiration inhibited the oxygen uptake by 63.4%. A mixture of SNP 1 mmol litre-1 and glutathione (GSH) 1 mmol litre-1 inhibited the oxygen uptake more markedly (by 75.9%). The cyanide concentrations were 0.01 mmol litre-1 with SNP alone and 0.15 mmol litre-1 with the mixture of SNP and GSH. Cyanide production from SNP in the presence of various reducing agents was studied in potassium phosphate 0.1 mol litre-1 buffer solution (pH 7.4) incubated at 37 degrees C. Cyanide was liberated markedly from SNP in the presence of GSH or ascorbate. Less cyanide was produced in the presence of NADH or NADPH. The rate of production of cyanide was dependent entirely upon the concentration of each reducing agent added. No cyanide was liberated when sodium dithionite or the oxidized forms of GSH, NAD or NADP were used. It was concluded that SNP is degradated to cyanide by a hydrogen donor and that the cyanide liberated in this manner inhibits the cytochrome oxidase activity of mitochondria in vivo.
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PMID:Inhibition of mitochondrial respiration by sodium nitroprusside and the mechanism of cyanide liberation. 58

Both di- and triglycerides were synthesized when microsomes isolated from mammary glands of lactating mice were incubated with dihydroxyacetone phosphate (DHAP), 1(-14)C)palmitate, ATP, CoASH, GSH, KF, MgC12, and NADPH. When NADH replaced NADPH, glyceride synthesis was very low. In the absence of either NADPH or NADH, DHAP was acylated to palmityl-DHAP. Since microsomes do not have glycerol 3-phosphate NAD:oxidoreductase activity , we inferred that glycerol 3-phosphate (GP) is not an intermediate in triglyceride biosynthesis from DHAP. This reductase, present in the cytosol, was active only with NADH. With the same concentration of either GP or DHAP, microsomes yielded essentially similar amounts of di- and triglycerides. Mitochondria, while capable of synthesizing palmityl-DHAP, did not produce di- and triglycerides.
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PMID:Triglyceride synthesis from dihydroxyacetone phosphate and palmitate by microsomes from mammary glands of lactating mice. 62 19

Rhodopseudomonas acidophila strain 10050, grown anaerobically in the light on methanol, contained a methanol and formaldehyde dehydrogenase which could be coupled to phenazine methosulphate; an NAD-linked formaldehyde dehydrogenase which required GSH for activity; and an NAD-linked formate dehydrogenase. The specific activities of these enzymes varied in a non-coordinate manner when the organism was grown on different alcohols, formate or succinate. The affinity of the phenazine methosulphate linked methanol dehydrogenase for methanol was increased 10-fold if the cell-free extract was prepared and assayed in the absence of oxygen. Pulse-labelling experiments with [14C5methanol and [14C]bicarbonate indicated that fixation of carbon dioxide occurred via the ribulose diphosphate cycle and C3 + CO 2 fixation reaction(s). No evidence was obtained for operation of a reduced C1 fixation sequence. This conclusion was borne out by the enzyme content of cell-free extracts of the organism.
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PMID:Metabolism of methanol by Rhodopseudomonas acidophila. 95 May 54

Dicumarol, often used as a specific inhibitor of DT diaphorase (NAD(P)H:(quinone-acceptor) oxidoreductase; EC 1.6.99.2), was found to potently inhibit GSH transferases (EC 2.5.1.18). Dicumarol exhibited an IC50 of 11 microM in inhibiting the conjugation of 1-chloro-2,4-dinitrobenzene (50 microM) by GSH transferase GT-8.7, the major hepatic class mu isoenzyme of CD-1 mice. The activities of GT-8.7 and of the class pi isoenzyme, GT-9.0, toward a carcinogenic substrate, 4-nitroquinoline 1-oxide (100 microM), were inhibited by dicumarol with IC50 values of 14 and 9 microM, respectively. Dicumarol also affected GSH peroxidase II activity, inhibiting the reduction of cumene hydroperoxide by GT-10.6, the predominant class alpha GSH transferase of mouse liver, with an IC50 of 14 microM. GSH peroxidase I (EC 1.11.1.9) and GSH peroxidase II activities were resolved by chromatography of liver and testis cytosols. While inhibiting GSH peroxidase II with IC50 of 9-10 microM, dicumarol did not affect the activity of the selenoenzyme, GSH peroxidase I. Whereas several other non-substrate ligands were more potent inhibitors of 1-chloro-2,4-dinitrobenzene conjugation, dicumarol effectively inhibited GSH transferase and GSH peroxidase II activities in the range of dicumarol concentrations frequently used for detection of DT diaphorase action. These results indicate that physiological consequences resulting from the use of supramicromolar concentrations of dicumarol should not be interpreted in terms of DT diaphorase inhibition alone.
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PMID:Inhibition of mouse glutathione transferases and glutathione peroxidase II by dicumarol and other ligands. 138 26

A concentration-dependent elevation of intracellular calcium ([Ca2+]i) and oxidation of NAD(P)H occurred in alveolar macrophages during exposure to sublethal tert-butylhydroperoxide concentrations (tBOOH) (< or = 100 microM in 1 ml with 1 x 10(6) cells). Oxidation of NAD(P)H preceded a rise in [Ca2+]i. The elevation of [Ca2+]i was reversible at < 50 microM tBOOH exposure and the return to the steady state [Ca2+]i correlated temporally with repletion of NAD(P)H. At > 50 microM tBOOH, the changes in NAD(P)H and [Ca2+]i were sustained. The relative contributions of NADPH and NADH oxidation were examined by varying the substrates supplying reducing equivalents and by inhibiting glutathione reductase activity. The results suggested that at < 50 microM tBOOH, oxidation of NADPH predominated, while at > 50 microM tBOOH, NADH oxidation predominated. A complex relationship between the relative roles of NADPH and NADH oxidation and the elevation of [Ca2+]i was revealed: (i) reversible oxidation of NADPH is associated with the initial and reversible elevation of [Ca2+]i at < 50 microM tBOOH; (ii) the sustained elevation of [Ca2+]i at > 50 microM tBOOH correlates with the sustained oxidation of NADH; and (iii) the changes in [Ca2+]i did not depend on influx of extracellular Ca2+. We speculate that at low tBOOH, Ca2+ was released from the NADPH/NADP(+)-sensitive mitochondrial Ca2+ pool while higher tBOOH caused additional Ca2+ release from GSH/GSSG-sensitive nonmitochondrial Ca2+ pools with sustained elevation of [Ca2+]i due to decreased mitochondrial Ca2+ reuptake.
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PMID:Sublethal oxidant stress induces a reversible increase in intracellular calcium dependent on NAD(P)H oxidation in rat alveolar macrophages. 144 55

Sodium selenite and selenomethionine were investigated as possible causative factors for the induction of Degnala disease syndrome in twelve buffalo (Bubalus bubalis) calves divided into three groups of four. Group 1 was the control group and received no additional selenium. Sodium selenite and selenomethionine were given daily as intramuscular injections on a selenium-equivalent basis, with a weekly increment in the dose of 0.05 mg Se/kg live weight from 0.05 to 0.20 mg Se/kg live weight per day, in groups 2 and 3 respectively. Only one animal from group 3 manifested the lesions of Degnala disease. The blood Se concentration and erythrocyte glutathione peroxidase (EC 1.11.1.9; GSH-Px) activity were both greater in groups 2 and 3 than in control group 1. The overall blood Se concentration was 0.22 (SE 0.01), 0.38 (SE 0.12) and 0.77 (SE 0.20) micrograms Se/ml in groups 1 to 3 respectively with corresponding GSH-Px activities of 63.84 (SE 7.38), 88.37 (SE 12.38) and 165.32 (SE 40.62) enzyme units/mg protein. Erythrocyte glutathione reductase (NAD(P)H) (EC 1.6.4.2) activity was not affected by treatment but reduced glutathione content was lower in groups 2 and 3. Liver adenosylmethionine, estimated at autopsy, was lowest (22.87 (SE 6.17) mumol/g) in group 3, and greatest (102.63 (SE 9.39) mumol/g) in group 1 (P less than 0.01). Organic Se sources seemed to accumulate in tissues more than inorganic sources, and might be the causative toxic factors of Degnala disease.
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PMID:Influence of different sources of injected selenium on certain enzymes, glutathione and adenosylmethionine concentration in buffalo (Bubalus bubalis) calves. 166 70

The phenotypic expression of multidrug resistance by the doxorubicin-selected AdrR human breast tumor cell line is associated with overexpression of plasma membrane P-170 glycoprotein and increased cytosolic selenium-dependent GSH-peroxidase activity relative to the parental MCF-7 wild-type line (WT). To determine whether doxorubicin resistance by AdrR cells persists in vivo, and to further investigate the possibility of biochemical differences between WT and AdrR solid tumors, both tumor cell lines were grown as subcutaneous xenografts in athymic nude mice. Tumorigenicity depended upon cell inoculation burden, and tumor incidence was similar for both cell lines (greater than 80% tumor takes at 10(7) cells/mouse) at 14 days, provided 17 beta-estradiol was supplied to the animals bearing the WT tumors. However, the growth rate for the AdrR xenografts was only about half that of WT xenografts. Doxorubicin (2-8 mg/kg, i.p., injected weekly) significantly diminished the growth of the WT tumors, but AdrR solid tumors failed to respond to doxorubicin. The accumulation of 14C-labeled doxorubicin was 2-fold greater in WT xenografts that in AdrR, although there were no differences in host organ drug levels in mice bearing either type of tumors. Membrane P-170 glycoprotein mRNA was detected by slot-blot analysis in the AdrR tumors, but not in WT. Electron spin resonance 5,5-dimethylpyrroline-N-oxide-spin-trapping experiments with microsomes and mitochondria from WT and AdrR xenographs demonstrated a 2-fold greater oxygen radical (superoxide and hydroxyl) formation from activated doxorubicin with WT xenographs compared to AdrR. Selenium-dependent glutathione (GSH)-peroxidase, superoxide dismutase and GSH-S-aryltransferase activities in AdrR xenografts were elevated relative to WT. Although the activities of the latter two enzymes were similar to those measured in both tumor cell lines, GSH-peroxidase activities were elevated 70-fold (WT) and 10-fold (AdrR) in xenografts compared to tumor cells. In contrast, in both WT and AdrR solid tumors in vivo, catalase, NAD(P)H-oxidoreductases, and glutathione disulfide (GSSG)-reductase activities, and GSH and GSSG levels were not markedly different, and were essentially the same as in cells in vitro. Like the MDR cells in culture, AdrR tumor xenografts were extremely resistant to doxorubicin and retained most of the characteristics of the altered phenotype. These results suggest that WT and AdrR breast tumor xenografts provide a useful model for the study of biochemical and pharmacological mechanisms of drug resistance by solid tumors in vivo.
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PMID:Biochemical and pharmacological characterization of MCF-7 drug-sensitive and AdrR multidrug-resistant human breast tumor xenografts in athymic nude mice. 167 69

Induction of glutathione transferases (EC. 2.5.1.18), NAD(P)H:(quinone-acceptor) oxidoreductase (EC 1.6.99.2; quinone reductase) and other detoxification enzymes is a major mechanism for protecting cells against the toxicities of electrophiles, including many carcinogens. Although inducers of these two enzymes belong to many different chemical classes, they nevertheless contain (or acquire by metabolism) electrophilic centres that appear to be essential for inclusive activity, and many inducers are Michael reaction acceptors [Talalay, De Long & Prochaska (1988) Proc. Natl. Acad. Sci. U.S.A., 85, 8261-8265]. The inducers therefore share structural and electronic features with glutathione transferase substrates. To define these features more precisely, we examined the inductive potencies (by measuring quinone reductase in murine hepatoma cells) of two types of glutathione transferase substrates: a series of 1-chloro-2-nitrobenzenes bearing para-oriented electron-donating or -withdrawing substituents and a wide variety of other commonly used and structurally unrelated glutathione transferase substrates. We conclude that virtually all glutathione transferase substrates are inducers, and their potencies in the nitrobenzene series correlate linearly with the Hammett sigma or sigma- values of the aromatic substituents, precisely as previously reported for their efficiencies as glutathione transferase substrates. More detailed information on the electronic requirements for inductive activity was obtained with a series of methyl trans-cinnamates bearing electron-withdrawing or -donating substituents on the aromatic ring, and in which the electronic densities at the olefinic and adjacent carbon atoms were measured by 13C n.m.r. Electron-withdrawing meta-substituents markedly enhance inductive potency in parallel with their increased non-enzymic reactivity with GSH. Thus, methyl 3-bromo-, 3-nitro- and 3-chloro-cinnamates are 21, 14 and 8 times more potent inducers than the parent methyl cinnamate. This finding permits the design of more potent inducers, which are important for elucidation of the molecular mechanisms of induction.
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PMID:The potency of inducers of NAD(P)H:(quinone-acceptor) oxidoreductase parallels their efficiency as substrates for glutathione transferases. Structural and electronic correlations. 190


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