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

To develop a method for the detection of surface-confined peptides containing cysteine residues or oligodeoxynucleotides (ODNs) whose 3' ends modified with thiol groups, and a thiol-specific fluorescent cross-linker, N-(9-acridinyl) maleimide (NAM) was used. The peptides studied herein include both the oxidized and reduced forms of glutathione, and a hexapeptide (FT). Peptides are first attached onto the activated 11-mercaptoundecanoic acid (MUA)-terminated alkanethiol self-assembled monolayers (SAMs) and then derivatized with NAM. The cysteine residues was determined by using electrochemical desorption and fluorescence detection. GSH concentration as low as 40 pmol x L(-1) can be measured. The fluorescence intensity in the case of FT is about 3 times as high as that for GSH, which is consistent with the molar ratio of cysteine residues in these two molecules. The analytical performance of gene analysis was also evaluated through the analyses of a complementary target and targets with varying numbers of mismatching bases. The method described here is simple, sensitive, reproducible, and does not require sophisticated analytical instrumentation and separation procedures.
 ...
PMID:[Determination of the cysteine residues in the surface-confined biomolecules by using electrochemical desorption and fluorescence detection]. 1835 39

Chitosan membrane with glutathione reductase and sulfhydryl oxidase (SOX) was subsequently integrated onto the surface of spectrographic graphite rods for obtaining a glutathione biosensor. The working principle was based on the monitoring of O(2) consumption that correlates the concentration of glutathione during the enzymatic reaction. A linear relationship between sensor response and concentration was obtained between 0.5 and 2.0 mM for oxidized glutathione (GSSG), and 0.2-1.0 mM for reduced glutathione (GSH) in the presence of 2 microM nicotinamide adenine dinucleotide phosphate (NADPH) under the optimum working conditions. Also, reduced/oxidized glutathione were separated by HPLC and utility of bienzymatic system was investigated as an electrochemical detector for the analysis of these compounds. All data were given as a comparison of two systems: biosensor and diode array detector (DAD).
 ...
PMID:Biosensing approach for glutathione detection using glutathione reductase and sulfhydryl oxidase bienzymatic system. 1837 8

The mammalian antizyme (AZ) promotes ubiqutin-independent degradation of ornithine decarboxylase, a key enzyme in polyamine biosynthesis. This study shows that AZ suppression in human lung carcinoma A549 cells caused growth defects and death, but made the cells resistant to DNA damaging agents such as gamma-radiation and cisplatin. In these cells, the cellular redox potential (glutathione/glutathione disulfide [GSH/GSSG] ratio) was increased and thus intracellular reactive oxygen species were severely diminished, which might cause growth defects and cell death. The increase of cellular redox potential was mainly caused by dramatic increase of the cytoplasmic nicotinamide adenine dinucleotide phosphate (NADP)(+)-dependent isocitrate dehydrogenase, which generates the reducing equivalents NADPH. In the AZ-suppressed cells, the hypoxia inducible factor 1alpha (HIF-1alpha) was also increased. As in other cases which showed an increment of HIF-1alpha and the cellular redox potential, the AZ-suppressed cells showed resistance to gamma-radiation and anticancer drugs. Therefore, these facts might be considered as important for the use of radio- and chemotherapy on tumor cells which show an unbalance in their polyamine levels.
 ...
PMID:Antizyme suppression leads to an increment of the cellular redox potential and an induction of HIF-1alpha: its involvement in resistance to gamma-radiation. 1848 90

We have earlier shown that nicotinamide (NIC) and nicotinic acid (NiA) can induce defence-related metabolism in plant cells; e.g. increase the level of glutathione. Here we investigated if NIC and NiA could increase the metal tolerance in metal sensitive clones of Salix viminalis and whether this would be mediated via increased glutathione level. Salix clones, sensitive or tolerant to zinc (Zn), copper (Cu) and cadmium (Cd) were grown in the presence of heavy metals (Cd, Cu or Zn) or NIC and NiA as well as in combination. In addition, the influence of N-acetyl-cystein (NAC) and l-2-oxothiazolidine 4-carboxylate (OTC), stimulators of reduced glutathione (GSH) biosynthesis, and the glutathione biosynthesis inhibitor buthionine sulfoximine (BSO) was analysed. Tolerance was measured as effects on root and shoot dry weight, and the glutathione and metal concentrations in the tissues were analysed. Results showed that NIC and NiA decreased the toxic effects of Cd, Cu and Zn on growth significantly in sensitive clones, but also to some extent in tolerant clones. However, the glutathione level and metal concentration did not change by NIC or NiA addition. Treatment with NAC, OTC or BSO did not per se influence the sensitivity to Cd, although the glutathione level increased in the presence of NAC and OTC and decreased in response to BSO. The results suggest that NIC and NiA increased the defence against heavy metals but not via glutathione formation per se.
 ...
PMID:Increased metal tolerance in Salix by nicotinamide and nicotinic acid. 1852 11

Proton pump inhibitors exert their preventive and healing effects on gastropathy induced by nonsteroidal anti-inflammatory drug (NSAIDs) by a dual action: the antisecretory and the antioxidant effect. The latter was investigated by using esomeprazole against indomethacin-induced gastric mucosa lesions in rats and assessed by a histomorphometric analysis. Treatment by intragastric gavage were 1% methocel as vehicle; esomeprazole 10, 30, or 60 micromol/kg; indomethacin 100 micromol/kg; and esomeprazole 10, 30, or 60 micromol/kg plus indomethacin 100 micromol/kg. The evaluation of glutathione (GSH) levels and respiratory chain complex activities [nicotinamide adenine dinucleotide, reduced (NADH)-ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome C reductase, cytochrome oxidase] was performed in the isolated gastric mucosa. Esomeprazole (10-60 micromol/kg) dose dependently reversed, up to complete recovery, the inhibitory effect of indomethacin on GSH levels (approximately 60% inhibition) and mitochondrial enzyme activities (inhibition ranging from 60% to 75%). Indomethacin-induced mucosal injuries were reduced by esomeprazole. Thus, in addition to inhibiting acid secretion, the gastroprotective effect of esomeprazole can be ascribed to a reduction in gastric oxidative injury.
 ...
PMID:Effects of esomeprazole on glutathione levels and mitochondrial oxidative phosphorylation in the gastric mucosa of rats treated with indomethacin. 1854 84

In pharmacological doses, nicotinic acid (niacin) reduces myocardial infarction, stroke and atherosclerosis. The beneficial effects of niacin on lipoproteins are thought to mediate these effects. We hypothesized that niacin inhibits oxidative stress and redox-sensitive inflammatory genes that play a critical role in early atherogenesis. In cultured human aortic endothelial cells (HAEC), niacin increased nicotinamide adenine dinucleotide phosphate (NAD(P)H) levels by 54% and reduced glutathione (GSH) by 98%. Niacin inhibited: (a) angiotensin II (ANG II)-induced reactive oxygen species (ROS) production by 24-86%, (b) low density lipoprotein (LDL) oxidation by 60%, (c) tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation by 46%, vascular cell adhesion molecule-1 (VCAM-1) by 77-93%, monocyte chemotactic protein-1 (MCP-1) secretion by 34-124%, and (d) in a functional assay TNF-alpha-induced monocyte adhesion to HAEC (41-54%). These findings indicate for the first time that niacin inhibits vascular inflammation by decreasing endothelial ROS production and subsequent LDL oxidation and inflammatory cytokine production, key events involved in atherogenesis. Initial data presented herein support the novel concept that niacin has vascular anti-inflammatory and potentially anti-atherosclerotic properties independent of its effects on lipid regulation.
 ...
PMID:Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells. 1855 65

Dantrolene, a drug used to treat malignant hyperthermia, inhibits abnormal Ca2+ release from the sarcoplasmic reticulum. Glutathione reductase (Glutathione: NADP+ oxidoreductase, EC 1.8.1.7), a member of the pyridine-nucleotide disulfide oxidoreductase family of flavoenzymes, catalyzes the reduction of glutathione disulfide (GSSG) to reduced form (GSH) in the presence of nicotinamide adenine dinucleotide phosphate (NADPH). In the present study, the in vitro effects of dantrolene on human erythrocyte glutathione reductase were investigated. For this purpose, initially, human erythrocyte glutathione reductase was purified 2555.56 fold in a yield of 29.74% using both 2',5'-ADP Sepharose-4B affinity gel chromatography and Sephadex G-200 gel filtration chromatography. The purity of the enzyme was controlled by sodium dodecyle sulfate (SDS)-polyacrylamide gel electrophoresis (SDS-PAGE) which showed a single band. A constant temperature (+4 degrees C) was maintained during the purification process. Enzyme activity was determined with the Beutler method at 340 nm by means of a spectrophotometer. Dantrolene showed remarkable in vitro inhibitory effects on the enzyme. Ki constant and 50% inhibitory concentration (IC50) value for dantrolene were determined by Lineweaver-Burk graphs and plotting activity % vs. [I], respectively. Ki constant for dantrolene was found to be 0.1116+/-0.04 mM; IC50 value was 0.0523 mM. Dantrolene displayed non-competitive inhibition.
 ...
PMID:Dantrolene inhibits human erythrocyte glutathione reductase. 1898 69

Selenium deficiency has been reported to result in an extraordinary decrease of glutathione peroxidase (GSH-Px) and, reversely, an increase of detoxifying enzymes such as glutathione-S-transferase (GST), uridine-5'-diphosphate glucuronosyltransferase (UGT), nicotinamide-dependent quinine oxidoreductase (NQO1; DT-diaphorase), and epoxide hydrolase without significantly affecting cytochrome P450 activity. However, little is known about the effects on aldehyde oxidase 1 (AOX1) activity towards various kinds of aldehydes and N-heterocyclic aromatic compounds. The aim of this study is to clarify the effects of selenium deficiency on AOX1 in rats. As expected, selenium deficiency was confirmed by the extremely low activity of GSH-Px along with the increased activities of GST and DT-diaphorase. AOX1 activity towards vanillin and (S)-RS-8359 was increased by selenium deficiency, and that corresponded to an increase of AOX1 protein level but not to a decreased AOX1 mRNA level. It has been documented that the assembly of the catalytically active holoenzyme forms of the molybdo-flavoenzyme family is very complex and is controlled through transcriptional and translational events by many gene products. In addition, selenium deficiency has been known to cause oxidative stress that leads to an increase of AOX1 activity. Furthermore, aldehyde oxidase homolog 1 (AOH1) with properties similar to AOX1 is present in rodent liver. All the reports suggest that the mechanisms by which selenium deficiency increases AOX1 activity are highly complicated and investigated from different points of view.
 ...
PMID:Effects of selenium deficiency on aldehyde oxidase 1 in rats. 1918 74

We experimented with a mathematical model for 1-carbon metabolism and glutathione (GSH) synthesis to investigate the effects of vitamin B-6 deficiency on the reaction velocities and metabolite concentrations in this metabolic network. The mathematical model enabled us to independently alter the activities of each of the 5 vitamin B-6-dependent enzymes and thus determine which inhibitions were responsible for the experimentally observed consequences of a vitamin B-6 deficiency. The effect of vitamin B-6 deficiency on serine and glycine concentrations in tissues and plasma was almost entirely due to its effects on the activity of glycine decarboxylase. The effect of vitamin B-6 restriction on GSH concentrations appeared to be indirect, arising from the fact that vitamin B-6 restriction increases oxidative stress, which, in turn, affects several enzymes in 1-carbon metabolism as well as the GSH transporter. Vitamin B-6 restriction causes an abnormally high and prolonged homocysteine response to a methionine load test. This effect appeared to be mediated solely by its effects on cystathionine beta-synthase. Reduction of the enzymatic activity of serine hydroxymethyltransferase (SHMT) had negligible effects on most metabolite concentrations and reaction velocities. Reduction or total elimination of cytoplasmic SHMT had a surprisingly moderate effect on metabolite concentrations and reaction velocities. This corresponds to the experimental findings that a reduction in the enzymatic activity of SHMT has little effect on 1-carbon metabolism. Our simulations showed that the primary function of SHMT was to increase the rate by which the glycine-serine balance was reequilibrated after a perturbation.
 ...
PMID:A mathematical model gives insights into the effects of vitamin B-6 deficiency on 1-carbon and glutathione metabolism. 1924 83

The metabolic syndrome is often described as a group of risk factors associated with diabetes. These risk factors include, but are not limited to, such conditions as insulin resistance, obesity, high blood pressure, and oxidant stress. Here, we report on a tool that may provide some clarity on the relationship between some of these associated risk factors, especially oxidant stress and hypertension. Specifically, we describe the ability to simultaneously monitor nicotinamide dinucleotide phosphate (NADPH), reduced glutathione (GSH), and shear-induced adenosine triphosphate (ATP) release from erythrocytes using luminescence detection on a microfabricated device. The measurements are performed by delivering erythrocyte lysate (for the NADPH and GSH measurements, two analytes indicative of oxidative stress) or whole red blood cells (RBCs) (for the determination of ATP release from the cells) to an array of wells that contain the necessary reagents to generate a luminescence emission that is proportional to analyte concentration. A fluorescence macrostereomicroscope enables whole-chip imaging of the resultant emission. The concentrations of each NADPH and GSH contained within a 0.7% erythrocyte solution were determined to be 31.06 +/- 4.12 and 22.55 +/- 2.47 microM, respectively, and the average ATP released from a nonlysed 7% erythrocyte solution was determined to be 0.54 +/- 0.04 microM. Collectively, the device represents a precursor to subsequent merging of microfluidics and microtiter-plate technology for high-throughput assessment of metabolite profiles in the diabetic erythrocyte.
 ...
PMID:Personalized metabolic assessment of erythrocytes using microfluidic delivery to an array of luminescent wells. 1930 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>