Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:7732-18-5 (water)
 694,341 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crystal structure of class Pi glutathione S-transferase from porcine lung (pGST P1-1) in complex with glutathione sulphonate has been refined at 2.11 A resolution, to a crystallographic R-factor of 16.5% for 21, 165 unique reflections. The refined structure includes 3314 protein atoms, 46 inhibitor (glutathione sulphonate) atoms and 254 water molecules. The model shows good stereochemistry, with root-mean-square deviations from ideal bond lengths and bond angles of 0.011 A and 2.8 degrees, respectively. The estimated root-mean-square co-ordinate error is 0.2 A. The protein is a dimer assembled from identical subunits of 207 amino acid residues. The tertiary structure of the pGST P1 subunit is organized as two domains, the N-terminal domain (domain I, residues 1 to 74) and the larger C-terminal domain (domain II, residues 81 to 207). Glutathione sulphonate, a competitive inhibitor, binds to the G-site region (i.e. the glutathione-binding region) of the active site located on each subunit. Each G-site is, however, structurally dependent of the neighbouring subunit as structural elements forming a fully functional G-site are provided by both subunits, with domain I as the major supporting framework. A number of direct and water-mediated polar interactions are involved in sequestering the glutathione analogue at the G-site. The extended conformation assumed by the enzyme-bound inhibitor as well as the strategic interactions between inhibitor and protein, closely resemble those observed for the physiological substrate, reduced glutathione bound at the active site of class Mu glutathione S-transferase 3-3. Hydrogen bonding between the sulphonyl moiety of the inhibitor and the hydroxyl group of an evolutionary conserved tyrosine residue, Tyr7, provides the first direct structural evidence for a catalytic protein group in glutathione S-transferases that is involved in the activation of the substrate glutathione. The catalytic role for Tyr7 has subsequently been confirmed by mutagenesis and kinetic studies. Comparison of the known crystal structures for class Pi, class Mu and class Alpha isoenzymes, indicates that the cytosolic glutathione S-transferases share a common fold and that the structural features for catalysis are similar.
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PMID:Refined crystal structure of porcine class Pi glutathione S-transferase (pGST P1-1) at 2.1 A resolution. 793 43

By 1915 the very complex life cycles of all the major schistosomes of man had been completely worked out. The disease could be attacked by removing the adult worms with drugs, by eliminating the snail hosts by habitat modifications, and by the provision of safe water supplies. Effective drugs, e.g., trivalent antimonials, were introduced in 1918. In the 1920s copper sulphate was shown to be lethal to the aquatic vectors of S. mansoni and S. haematobium and lime was first used to attack the amphibious vectors of S. japonicum. In the search for antischistosome vaccines several protective antigens have been defined at the molecular level and are being evaluated in animal models. The characteristic decline in age-specific prevalence and intensity of infection seen in S. haematobium and S. mansoni endemic areas is largely due to the gradual development of acquired immunity. In the 1970s, work involving immunization with irradiation attenuated or heterologous, normal cercariae, using several different animal models demonstrated that short-lived larval infections could reliably induce significant levels of resistance to challenge infection with normal cercariae. The concomitant immunity premise led to the purification of the first such antigen, the 38 kDa S. mansoni surface glycoprotein GP38. Vaccination with KLH also protected rats against S. mansoni infection and elicited anti-GP38 antibodies which could passively protect rats; deglycosylation of KLH abolished these properties. S. mansoni GST was identified for protective antigens suitable for gene cloning. The protective efficacy of combined GST/KLH S. japonicum vaccines and the efficacy of recombinant-derived GSTs, and of S. japonicum paramyosin are being explored in sheep and bovines in China. Two irradiated vaccine dominant antigens have been cloned and sequenced, IVGS3 and IVRB4, which are now being tested in protection experiments in rodents prior to trials on large animals in China.
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PMID:Schistosomiasis vaccines: Farewell to the God of Plague? 793 21

1. The induction of phase I and II enzymes in the liver of the male F344 rat drinking 2% (w/v) solutions of green or black tea for 6 weeks was investigated. Also studied were glutathione (GSH) and cyst(e)ine in blood, liver and kidney, as well as serum cholesterol, HDL cholesterol, triglycerides, and total and free testosterone. 2. The total carbon monoxide-discernible liver P450, b5 and NADPH-cytochrome c(P450) reductase activities were similar in all groups. 3. There were significant increases in liver of rat drinking green or black tea of P4501A1, 1A2 and 2B1 activities, but no change in P4502E1 and 3A4 activities. Of the phase II enzymes, UDP-glucuronyltransferase was increased, but glutathione S-transferase was not. 4. Serum GSH was higher in the group administered black tea, but GSH and cyst(e)ine in other groups was at control levels. Serum cholesterol was lower in rat given black compared with green tea. Triglycerides had a declining trend after green and black tea exposure compared with water controls. Free and total testosterone were not affected. 5. Thus, beverages widely used by man altered host biochemistry as regards specific phase I and II enzymes in liver of rat and specific serum parameters.
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PMID:Effects of green and black tea on hepatic xenobiotic metabolizing systems in the male F344 rat. 801 87

The major water-soluble proteins--or crystallins--of the eye lens are either identical to or derived from proteins with non-refractive functions in numerous tissues. In general, the recruitment of crystallins has come from metabolic enzymes (usually with detoxification functions) or stress proteins. Some crystallins have been recruited without duplication of the original gene (i.e., lactate dehydrogenase B and alpha-enolase), while others have incurred one (i.e., argininosuccinate lyase and a small heat shock protein) or several (i.e., glutathione S-transferase) gene duplications. Enzyme (or stress protein)-crystallins often maintain their non-refractive function in the lens and/or other tissues as well as their refractive role, a process we call gene sharing. alpha-Crystallin/small heat shock protein/molecular chaperone is of special interest since it is the major crystallin of humans. There are two alpha-crystallin genes (alpha A and alpha B), with alpha B retaining the full functions of a small heat shock protein. Here we describe recent evidence indicating that alpha A and alpha B have kinase activity, which would make them members of the enzyme-crystallins. We also describe various regulatory elements of the mouse alpha-crystallin genes responsible for their expression in the lens and, for alpha B, in skeletal muscle. Delineating the control elements for gene expression of these multifunctional protective proteins provides the foundations for their eventual use in gene therapy. Finally, comparison of the mouse and chicken alpha A-crystallin genes reveals similarities and differences in their functional cis-acting elements, indicative of evolution at the level of gene regulation.
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PMID:Recruitment of enzymes and stress proteins as lens crystallins. 803 55

In an investigation of the modulation of certain neonatal xenobiotic-metabolizing enzymes in liver of mouse pups postnatally exposed to selenium through the transmammary route, sodium selenite was administered in drinking water to lactating dams at the dose levels of 1 or 5 ppm from day 1 of lactation and continued daily for 14 or 21 days. The higher dose of selenium was found to increase the hepatic acid-soluble sulfhydryl content significantly after 21 days of treatment in dams, their pups (P < 0.01) and in the 14-day-old male pups (P < 0.05). Cytochrome b5 content decreased in the livers of dams that received 5 ppm selenium (P < 0.01) and in the F1 pups (P < 0.01) translactationally exposed to selenium for 14 days. Cytochrome P-450 content decreased in dams and pups exposed to 5 ppm selenium for 14 days and either dose for 21 days (P < 0.01). Hepatic glutathione S-transferase decreased in the dam that had received 5 ppm selenium for 14 days (P < 0.05) and in the 14-day-old pups (P < 0.01). Glutathione reductase and glutathione peroxidase activities decreased in both dams and pups (P < 0.01). The overall suppression of neonatal hepatic detoxification enzymes demonstrates that selenium may have far-reaching consequences on neonatal growth, development and drug pharmacokinetics.
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PMID:Translactational exposure of F1 mouse pups to selenium. 804 58

The effect of verapamil on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks and received i.p. injections of verapamil or vehicle every other day for 16 weeks from the start of the experiment. Pre-neoplastic and neoplastic lesions staining positive for gamma-glutamyl transpeptidase (GGT) or the placental type of glutathione-S-transferase (GST-P) were examined histochemically at week 16. Prolonged administration of verapamil resulted in a significant decrease in the number of GGT-positive and GST-P-positive lesions. The incidence and volume as a percentage of parenchyma of hepatocellular carcinomas were also significantly less in rats treated with verapamil than in controls. Administration of verapamil significantly decreased the labelling indices of pre-neoplastic lesions and adjacent liver. These findings indicate that verapamil inhibits hepatocarcinogenesis and that this may be related to its inhibitory effect on cell proliferation in neoplastic lesions and surrounding hepatocytes.
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PMID:Inhibition by verapamil of hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. 814 68

1. The acute combined effects of cadmium (Cd) and nickel (Ni) on rat hepatic glutathione S-transferase (GST) activities toward the substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB) and ethacrynic acid (EAA) were determined and compared to those of Cd or Ni alone. 2. Male adult rats (225-275 g) were administered either a single dose of Cd (3.58 mg CdCl2.H2O/kg, i.p.) 72 hr prior to sacrifice or a single dose of Ni (59.5 mg NiCl2.6H2O/kg, s.c.) 16 hr prior to sacrifice. For the combined treatment, animals received the single dose of Ni 56 hr after the single dose of Cd and they were killed 16 hr later. 3. Cd treatment alone did not produce any changes in the hepatic GST activities toward the substrates studied. 4. Ni treatment alone, however, significantly increased hepatic GST activity toward EAA whereas it was ineffective on GST activities for CDNB and DCNB. 5. Combined treatment of metals did not alter hepatic GST activities toward the substrates CDNB and DCNB. Hepatic GST activity for EAA, however, was significantly increased by the combined treatment. Nevertheless, the combined treatment did not augment the increase in GST activity for EAA noted by Ni treatment alone.
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PMID:Combined effects of cadmium and nickel on hepatic glutathione S-transferases in rats. 810 37

The target organ specificities of cell proliferation and histopathological lesion induction by 5 carcinogens having different target organs were evaluated using a multiorgan carcinogenesis bioassay. In Group 1, male F-344 rats aged 6 wk were sequentially treated with N-diethylnitrosamine (DEN, single 100-mg/kg ip injection, week 0), N-methyl-N-nitrosourea (MNU, 4 20-mg/kg ip injections, weeks 0-2), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, 0.05% in drinking water, weeks 0-2), N,N'-dimethylhydrazine (DMH, 4 40-mg/kg sc injections, weeks 2-4), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking water, weeks 2-4) during the first 4 wk. In Groups 2-6, rats were treated with only one of the above initiators, applied as in Group 1. Group 7 served as the no-treatment control. Bromouracil deoxyriboside (BUdR) labeling indices (LI) were counted in various organs at weeks 2 and 4. Numbers and areas of glutathione S-transferase placental form positive (GST-P+) liver foci were measured at weeks 2, 4, and 28. Preneoplastic or neoplastic lesion development was assessed at week 28. With regard to specific elevation of cell proliferation in target organs, BUdR LIs in the urinary bladder, liver, and colon were, respectively, increased in the BBN alone, DEN alone, and DMH alone treated groups as well as in Group 1. However, LIs of thyroid, lung, and kidney were also elevated by several carcinogens not including these organs in their carcinogenic target specificity. On the other hand, morphological lesions and GST-P+ foci were limited to Group 1 and the target organs of the corresponding carcinogen-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Target organ specificity of cell proliferation induced by various carcinogens. 811 20

The protection of Plasmodium vivax-parasitized red blood cells (PRBCs) against activated forms of oxygen was examined in relation to the non-parasitized and chloroquine-treated red blood cells. Increased parasitaemia was found to be accompanied with a decrease in the activities of enzymes of the glutathione system, namely glutathione peroxidase (GPx), glutathione reductase (GRx) and glutathione S-transferase (GTr) in the red blood cells (RBC) lysates. In contrast, however, the total amount of reduced glutathione (GSH) and the content of water-soluble antioxidant vitamin C was increased 2-3 fold over those of control RBCs. Chloroquine-treated red cells contained enzyme activities and antioxidant contents (GSH, vitamin C) comparable to those of control and non-parasitized red cells. Our results therefore indicate the oxidative stress experienced by RBCs during P. vivax infection and that this infection is accompanied with changes in the antioxidant defence system of the host, which are restored to near normal levels after treatment with chloroquine.
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PMID:Oxidative stress and antioxidant defence mechanism in Plasmodium vivax malaria before and after chloroquine treatment. 813 81

The effect of Shi-Quan-Da-Bu-Tang (TJ-48) on hepatocarcinogenesis induced by N-nitrosomorpholine (NNM) was investigated in male Sprague-Dawley rats. Rats were given drinking water containing NNM for 8 weeks, and also from the start of the experiment, regular chow pellets containing 2.0 or 4.0% TJ-48 until the end of the experiment. Preneoplastic and neoplastic lesions staining for the placental type of glutathione-S-transferase (GST-P) or gamma-glutamyl transpeptidase (GGT) were examined histochemically. In week 15, quantitative histological analysis showed that prolonged administration of either 2.0 or 4.0% TJ-48 in the diet significantly reduced the size, volume and/or number of GST-P-positive and GGT-positive hepatic lesions. This treatment also caused a significant increase in the proportion of interleukin-2 receptor-positive lymphocytes among the lymphocytes infiltrating the tumours as well as a significant decrease in the labelling index of preneoplastic lesions. These findings indicate that TJ-48 inhibits the growth of hepatic enzyme-altered lesions, and suggests that its effect may be in part due to activation of the immune system.
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PMID:Inhibition by shi-quan-da-bu-tang (TJ-48) of experimental hepatocarcinogenesis induced by N-nitrosomorpholine in Sprague-Dawley rats. 814 69


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