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Sample records for oral farnesyl transferase

  1. A phase II trial of R115777, an oral farnesyl transferase inhibitor, in      patients with advanced urothelial tract transitional cell carcinoma

    DEFF Research Database (Denmark)

    Rosenberg, Jonathan E.; Maase, Hans von der; Seigne, John D.

    2005-01-01

    BACKGROUND: R115777 is a potent farnesyl transferase inhibitor and has       significant antitumor effects in vitro and in vivo. METHODS: The objective       of the current study was to determine the objective response proportion in       patients with metastatic transitional cell carcinoma (TCC......) of the       urothelial tract who received treatment with R115777 at a dose of 300 mg       orally given twice daily for 21 days followed by 7 days of rest for every       4-week cycle. Thirty-four patients with TCC were enrolled in this Phase II       study. Patients were allowed to have received a maximum of one prior......       observed. CONCLUSIONS: The objective response rate of R115777 was not       sufficient to warrant future investigation in TCC as a single agent.       Preliminary evidence of the activity of R115777 in 2 chemotherapy-naive       patients may warrant further investigation in combination with first...

  2. Novel derivatives of aclacinomycin A block cancer cell migration through inhibition of farnesyl transferase.

    Science.gov (United States)

    Magi, Shigeyuki; Shitara, Tetsuo; Takemoto, Yasushi; Sawada, Masato; Kitagawa, Mitsuhiro; Tashiro, Etsu; Takahashi, Yoshikazu; Imoto, Masaya

    2013-03-01

    In the course of screening for an inhibitor of farnesyl transferase (FTase), we identified two compounds, N-benzyl-aclacinomycin A (ACM) and N-allyl-ACM, which are new derivatives of ACM. N-benzyl-ACM and N-allyl-ACM inhibited FTase activity with IC50 values of 0.86 and 2.93 μM, respectively. Not only ACM but also C-10 epimers of each ACM derivative failed to inhibit FTase. The inhibition of FTase by N-benzyl-ACM and N-allyl-ACM seems to be specific, because these two compounds did not inhibit geranylgeranyltransferase or geranylgeranyl pyrophosphate (GGPP) synthase up to 100 μM. In cultured A431 cells, N-benzyl-ACM and N-allyl-ACM also blocked both the membrane localization of H-Ras and activation of the H-Ras-dependent PI3K/Akt pathway. In addition, they inhibited epidermal growth factor (EGF)-induced migration of A431 cells. Thus, N-benzyl-ACM and N-allyl-ACM inhibited EGF-induced migration of A431 cells by inhibiting the farnesylation of H-Ras and subsequent H-Ras-dependent activation of the PI3K/Akt pathway.

  3. Farnesyl transferase inhibitors induce extended remissions in transgenic mice with mature B cell lymphomas

    Directory of Open Access Journals (Sweden)

    Refaeli Yosef

    2008-05-01

    Full Text Available Abstract Background We have used a mouse model based on overexpression of c-Myc in B cells genetically engineered to be self-reactive to test the hypothesis that farnesyl transferase inhibitors (FTIs can effectively treat mature B cell lymphomas. FTIs are undergoing clinical trials to treat both lymphoid and non-lymphoid malignancies and we wished to obtain evidence to support the inclusion of B cell lymphomas in future trials. Results We report that two FTIs, L-744,832 and SCH66336, blocked the growth of mature B cell lymphoma cells in vitro and in vivo. The FTI treatment affected the proliferation and survival of the transformed B cells to a greater extent than naïve B cells stimulated with antigen. In syngeneic mice transplanted with the transgenic lymphoma cells, L-744,832 treatment prevented the growth of the tumor cells and the morbidity associated with the resulting lymphoma progression. Tumors that arose from transplantation of the lymphoma cells regressed with as little as three days of treatment with L-744,832 or SCH66336. Treatment of these established lymphomas with L-744,832 for seven days led to long-term remission of the disease in approximately 25% of animals. Conclusion FTI treatment can block the proliferation and survival of self-reactive transformed B cells that overexpress Myc. In mice transplanted with mature B cell lymphomas, we found that FTI treatment led to regression of disease. FTIs warrant further consideration as therapeutic agents for mature B cell lymphomas and other lymphoid tumors.

  4. Heat-shock protein 40 is the key farnesylation target in meristem size control, abscisic acid signaling, and drought resistance.

    Science.gov (United States)

    Barghetti, Andrea; Sjögren, Lars; Floris, Maïna; Paredes, Esther Botterweg; Wenkel, Stephan; Brodersen, Peter

    2017-11-15

    Protein farnesylation is central to molecular cell biology. In plants, protein farnesyl transferase mutants are pleiotropic and exhibit defective meristem organization, hypersensitivity to the hormone abscisic acid, and increased drought resistance. The precise functions of protein farnesylation in plants remain incompletely understood because few relevant farnesylated targets have been identified. Here, we show that defective farnesylation of a single factor-heat-shock protein 40 (HSP40), encoded by the J2 and J3 genes-is sufficient to confer ABA hypersensitivity, drought resistance, late flowering, and enlarged meristems, indicating that altered function of chaperone client proteins underlies most farnesyl transferase mutant phenotypes. We also show that expression of an abiotic stress-related microRNA (miRNA) regulon controlled by the transcription factor SPL7 requires HSP40 farnesylation. Expression of a truncated SPL7 form mimicking its activated proteolysis fragment of the membrane-bound SPL7 precursor partially restores accumulation of SPL7-dependent miRNAs in farnesyl transferase mutants. These results implicate the pathway directing SPL7 activation from its membrane-bound precursor as an important target of farnesylated HSP40, consistent with our demonstration that HSP40 farnesylation facilitates its membrane association. The results also suggest that altered gene regulation via select miRNAs contributes to abiotic stress-related phenotypes of farnesyl transferase mutants. © 2017 Barghetti et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Inhibition of protein geranylgeranylation and farnesylation protects against graft-versus-host disease via effects on CD4 effector T cells.

    Science.gov (United States)

    Hechinger, Anne-Kathrin; Maas, Kristina; Dürr, Christoph; Leonhardt, Franziska; Prinz, Gabriele; Marks, Reinhard; Gerlach, Ulrike; Hofmann, Maike; Fisch, Paul; Finke, Jürgen; Pircher, Hanspeter; Zeiser, Robert

    2013-01-01

    Despite advances in immunosuppressive regimens, acute graft-versus-host disease remains a frequent complication of allogeneic hematopoietic cell transplantation. Pathogenic donor T cells are dependent on correct attachment of small GTPases to the cell membrane, mediated by farnesyl- or geranylgeranyl residues, which, therefore, constitute potential targets for graft-versus-host disease prophylaxis. A mouse model was used to study the impact of a farnesyl-transferase inhibitor and a geranylgeranyl-transferase inhibitor on acute graft-versus-host disease, anti-cytomegalovirus T-cell responses and graft-versus-leukemia activity. Treatment of mice undergoing allogeneic hematopoietic cell transplantation with farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor reduced the histological severity of graft-versus-host disease and prolonged survival significantly. Mechanistically, farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor treatment resulted in reduced alloantigen-driven expansion of CD4 T cells. In vivo treatment led to increased thymic cellularity and polyclonality of the T-cell receptor repertoire by reducing thymic graft-versus-host disease. These effects were absent when squalene production was blocked. The farnesyl-transferase inhibitor and geranylgeranyl-transferase inhibitor did not compromise CD8 function against leukemia cells or reconstitution of T cells that were subsequently responsible for anti-murine cytomegalovirus responses. In summary, we observed an immunomodulatory effect of inhibitors of farnesyl-transferase and geranylgeranyl-transferase on graft-versus-host disease, with enhanced functional immune reconstitution. In the light of the modest toxicity of farnesyl-transferase inhibitors such as tipifarnib in patients and the potent reduction of graft-versus-host disease in mice, farnesyl-transferase and geranylgeranyl-transferase inhibitors could help to reduce graft-versus-host disease significantly without

  6. Thymidylate Synthase, Thymidine Phosphorylase and Orotate Phosphoribosyl Transferase Levels as Predictive Factors of Chemotherapy in Oral Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Ogiuchi, Yosuke; Maruoka, Yasubumi; Ando, Tomohiro; Kobayashi, Makio; Ogiuchi, Hideki

    2008-01-01

    We conducted a clinicopathologic study on protein and mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) using biopsy tissue specimens before treatment. The mRNA levels have been measured in tumor cells microdissected from paraffin-embedded specimens (Danenberg Tumor Profile method: DTP method). We studied the mRNA and protein expression as effect predictive factors in chemotherapy. The subjects consisted of 20 cases of untreated oral squamous cell carcinoma who had undergone chemotherapy with TS-1 (16 males and 4 females, tongue in 8 cases, upper gingiva in 3 cases, lower gingiva in 3 cases, buccal mucosa in 5 cases and floor of the mouth in 1 case). TS gene expressions of the responders were lower than those for the nonresponders. Furthermore, regarding males who were less than 70 years of age, stage I and II, well differentiated type and tongue, TS mRNA expression of the responders were lower than that for the nonresponders. The mRNA expression of OPRT for the male responders was lower than that for the nonresponders. No remarkable difference was observed by immunohistochemistry. In this study, the measurement of the TS levels using the DTP method may potentially act as a predictive factor of antitumor effectiveness

  7. Photoaffinity labeling of undecaprenyl pyrophosphate synthetase with a farnesyl pyrophosphate analogue

    International Nuclear Information System (INIS)

    Baba, T.; Muth, J.; Allen, C.M.

    1985-01-01

    The prenyl transferase undecaprenyl pyrophosphate synthetase was partially purified from the cytosolic fraction of Escherichia coli. Its enzymic products were characterized as a family of cis-polyprenyl phosphates, which ranged in carbon number from C55 to C25. The enzyme is constituted of two subunits of approximately 30,000 molecular weight. A radiolabeled photolabile analogue of t,t-farnesyl pyrophosphate, [ 3 H]2-diazo-3-trifluoropropionyloxy geranyl pyrophosphate, was shown to label Lactobacillus plantarum and E. coli undecaprenyl pyrophosphate synthetase on UV irradiation in the presence of isopentenyl pyrophosphate and divalent cations. The only labeled polypeptide migrated on electrophoresis in a sodium dodecyl sulfate-polyacrylamide gel at a molecular weight of approximately 30,000. No protein was radiolabeled when the natural substrate, t,t-farnesyl pyrophosphate was included in the irradiation mixture. Irradiation in the presence of MgCl 2 without isopentenyl pyrophosphate gave less labeling of the polypeptide. Irradiation with only isopentenyl pyrophosphate gave little labeling of the polypeptide. When the enzyme was irradiated with 3H-photoprobe, [ 14 C]isopentenyl pyrophosphate, and MgCl 2 , the labeled polypeptide gave a ratio of 14 C/ 3 H that indicated the product must also bind to the enzyme on irradiation. These results demonstrate the ability to radiolabel the allylic pyrophosphate binding site and possibly product binding site of undecaprenyl pyrophosphate synthetase by a process which is favored when both cosubstrate and divalent cations are present

  8. Positive Foci of Glutathione S‐Transferase Placental Form in the Liver of Rats Given Furfural by Oral Administration

    Science.gov (United States)

    Shimizu, Akio; Nakamura, Yoshiyasu; Harada, Masaoki; Ono, Tetsuo; Sato, Kiyomi; Inoue, Tohru; Kanisawa, Masayoshi

    1989-01-01

    We observed GST‐P‐positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural‐containing diet (20–30 rag/kg diet) for 15–150 days, and killed 14 days after terminating furfural feeding. Immuno‐histochemical investigation of GST‐P‐positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural‐induced cirrhosis on chemical hepatocarcino‐genesis. PMID:2507483

  9. Propiconazole-enhanced hepatic cell proliferation is associated with dysregulation of the cholesterol biosynthesis pathway leading to activation of Erk1/2 through Ras farnesylation

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, Lynea A.; Moore, Tanya; Nesnow, Stephen, E-mail: nesnow.stephen@epa.gov

    2012-04-15

    Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic cholesterol metabolites and bile acids, and transcriptomic studies revealed that genes within the cholesterol biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up-regulated. Hepatic cell proliferation was also increased by propiconazole. AML12 immortalized hepatocytes were used to study propiconazole's effects on cell proliferation focusing on the dysregulation of cholesterol biosynthesis and resulting effects on Ras farnesylation and Erk1/2 activation as a primary pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway, increases cell proliferation in several cancer cell lines and tumors in vivo and serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are crucial in the farnesylation of the Ras protein by farnesyl transferase. Farnesylation targets Ras to the cell membrane where it is involved in signal transduction, including the mitogen-activated protein kinase (MAPK) pathway. In our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased cell proliferation in AML12 cells which was reduced by farnesyl transferase inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase inhibitor, indicating that this cell system responded to alterations in the cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased by propiconazole which was reversed by co-incubation with L-744,832 or simvastatin. Increasing concentrations of exogenous cholesterol muted the proliferative effects of propiconazole and the inhibitory effects of L-733,832, results ascribed to reduced stimulation of the endogenous cholesterol biosynthesis pathway. Western blot analysis of subcellular

  10. Transferases in Polymer Chemistry

    NARCIS (Netherlands)

    van der Vlist, Jeroen; Loos, Katja; Palmans, ARA; Heise, A

    2010-01-01

    Transferases are enzymes that catalyze reactions in which a group is transferred from one compound to another. This makes these enzymes ideal catalysts for polymerization reactions. In nature, transferases are responsible for the synthesis of many important natural macromolecules. In synthetic

  11. Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region.

    Science.gov (United States)

    Jang, Hyunbum; Abraham, Sherwin J; Chavan, Tanmay S; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I; Nussinov, Ruth; Gaponenko, Vadim

    2015-04-10

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

    Science.gov (United States)

    Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

  13. Chlorophyll a with a farnesyl tail in thermophilic cyanobacteria.

    Science.gov (United States)

    Wiwczar, Jessica M; LaFountain, Amy M; Wang, Jimin; Frank, Harry A; Brudvig, Gary W

    2017-11-01

    Photosystem II (PSII) of oxygenic photosynthetic organisms normally contains exclusively chlorophyll a (Chl a) as its major light-harvesting pigment. Chl a canonically consists of the chlorin headgroup with a 20-carbon, 4-isoprene unit, phytyl tail. We have examined the 1.9 Å crystal structure of PSII from thermophilic cyanobacteria reported by Shen and coworkers in 2012 (PDB accession of 3ARC/3WU2). A newly refined electron density map from this structure, presented here, reveals that some assignments of the cofactors may be different from those modeled in the 3ARC/3WU2 structure, including a specific Chl a that appears to have a truncated tail by one isoprene unit. We provide experimental evidence using high-performance liquid chromatography and mass spectrometry for a small population of Chl a esterified to a 15-carbon farnesyl tail in PSII of thermophilic cyanobacteria.

  14. Andrastin A and barceloneic acid metabolites, protein farnesyl transferase inhibitors from Penicillium alborcoremium: chemotaxonomic significance and pathological implications

    DEFF Research Database (Denmark)

    Overy, David Patrick; Larsen, Thomas Ostenfeld; Dalsgaard, P.W.

    2005-01-01

    A survey of Penicillium albocoremium was undertaken to identify potential taxonomic metabolite markers. One major and four minor metabolites were consistently produced by the 19 strains surveyed on three different media. Following purification and spectral studies, the metabolites were identified...

  15. Towards complete sets of farnesylated and geranylgeranylated proteins.

    Directory of Open Access Journals (Sweden)

    Sebastian Maurer-Stroh

    2007-04-01

    the selective farnesylation of targets with an evolutionary conserved modification site.

  16. Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate

    OpenAIRE

    Samoudi, Mojtaba; Omid Yeganeh, Negar; Shahbani Zahiri, Hossein; Shariati, Parvin; Hajhosseini, Reza

    2015-01-01

    Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli). Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transform...

  17. A novel approach towards the synthesis of pyrophosphate analogues of farnesyl pyrophosphate

    NARCIS (Netherlands)

    Valentijn, A.R.P.M.; Berg, O. van den; Marel, G.A. van der; Cohen, L.H.; Boom, J.H. van

    1994-01-01

    The synthesis of two new analogues (i.e. 3 and 4) of farnesyl pyrophosphate (FPP) containing a phosphonophosphate and a phosphonophosphonate moiety was accomplished via the phosphonomorpholidate. The latter was easily obtained by treatment of a phosphonic chloride with morpholine.

  18. Orented immobilization of farnesylated proteins by the thiol-ene reaction

    NARCIS (Netherlands)

    Weinrich, Dirk; Lin, Po-Chiao; Jonkheijm, Pascal; Nguyen, Uyen T.T.; Schröder, Hendrik; Niemeyer, Christof M.; Alexandrov, Kirill; Goody, Roger; Waldmann, Herbert

    2010-01-01

    Anchoring the protein: Proteins were immobilized rapidly under mild conditions by thiol-ene photocoupling between S-farnesyl groups attached to a genetically encodable “CAAX-box” tetrapeptide sequence (A is aliphatic) at the C terminus of the protein and surface-exposed thiols (see scheme). This

  19. Inhibition of Protein Farnesylation Arrests Adipogenesis and Affects PPARγ Expression and Activation in Differentiating Mesenchymal Stem Cells

    Science.gov (United States)

    Rivas, Daniel; Akter, Rahima; Duque, Gustavo

    2007-01-01

    Protein farnesylation is required for the activation of multiple proteins involved in cell differentiation and function. In white adipose tissue protein, farnesylation has shown to be essential for the successful differentiation of preadipocytes into adipocytes. We hypothesize that protein farnesylation is required for PPARγ2 expression and activation, and therefore for the differentiation of human mesenchymal stem cells (MSCs) into adipocytes. MSCs were plated and induced to differentiate into adipocytes for three weeks. Differentiating cells were treated with either an inhibitor of farnesylation (FTI-277) or vehicle alone. The effect of inhibition of farnesylation in differentiating adipocytes was determined by oil red O staining. Cell survival was quantified using MTS Formazan. Additionally, nuclear extracts were obtained and prelamin A, chaperon protein HDJ-2, PPARγ, and SREBP-1 were determined by western blot. Finally, DNA binding PPARγ activity was determined using an ELISA-based PPARγ activation quantification method. Treatment with an inhibitor of farnesylation (FTI-277) arrests adipogenesis without affecting cell survival. This effect was concomitant with lower levels of PPARγ expression and activity. Finally, accumulation of prelamin A induced an increased proportion of mature SREBP-1 which is known to affect PPARγ activity. In summary, inhibition of protein farnesylation arrests the adipogenic differentiation of MSCs and affects PPARγ expression and activity. PMID:18274630

  20. Identification of Farnesyl Pyrophosphate and N-Arachidonylglycine as Endogenous Ligands for GPR92*S⃞

    OpenAIRE

    Oh, Da Young; Yoon, Jung Min; Moon, Mi Jin; Hwang, Jong-Ik; Choe, Han; Lee, Ju Yeon; Kim, Jae Il; Kim, Sunoh; Rhim, Hyewhon; O'Dell, David K.; Walker, J. Michael; Na, Heung Sik; Lee, Min Goo; Kwon, Hyuk Bang; Kim, Kyungjin

    2008-01-01

    A series of small compounds acting at the orphan G protein-coupled receptor GPR92 were screened using a signaling pathway-specific reporter assay system. Lipid-derived molecules including farnesyl pyrophosphate (FPP), N-arachidonylglycine (NAG), and lysophosphatidic acid were found to activate GPR92. FPP and lysophosphatidic acid were able to activate both Gq/11- and Gs-mediated signaling pathways, whereas NAG activated only the Gq/11-mediated signaling pathway. Co...

  1. Carnitine palmityl transferase I deficiency

    NARCIS (Netherlands)

    Al-Aqeel, A. I.; Rashed, M. S.; Ruiter, J. P.; Al-Husseini, H. F.; Al-Amoudi, M. S.; Wanders, R. J.

    2001-01-01

    Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected

  2. Isolation and characterization of farnesyl diphosphate synthase from the cotton boll weevil, Anthonomus grandis.

    Science.gov (United States)

    Taban, A Huma; Tittiger, Claus; Blomquist, Gary J; Welch, William H

    2009-06-01

    Farnesyl diphosphate synthase (FPPS) catalyzes the consecutive condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate to form farnesyl diphosphate (FPP). In insects, FPP is used for the synthesis of ubiquinones, dolicols, protein prenyl groups, and juvenile hormone. A full-length cDNA of FPPS was cloned from the cotton boll weevil, Anthonomus grandis (AgFPPS). AgFPPS cDNA consists of 1,835 nucleotides and encodes a protein of 438 amino acids. The deduced amino acid sequence has high similarity to previously isolated insect FPPSs and other known FPPSs. Recombinant AgFPPS expressed in E. coli converted labeled isopentenyl diphosphate in the presence of dimethylallyl diphosphate to FPP. Southern blot analysis indicated the presence of a single copy gene. Using molecular modeling, the three-dimensional structure of coleopteran FPPS was determined and compared to the X-ray crystal structure of avian FPPS. The alpha-helical fold is conserved in AgFPPS and the size of the active site cavity is consistent with the enzyme being a FPPS. (c) 2009 Wiley Periodicals, Inc.

  3. Cloning and Characterization of Farnesyl Diphosphate Synthase Gene Involved in Triterpenoids Biosynthesis from Poria cocos

    Directory of Open Access Journals (Sweden)

    Jianrong Wang

    2014-12-01

    Full Text Available Poria cocos (P. cocos has long been used as traditional Chinese medicine and triterpenoids are the most important pharmacologically active constituents of this fungus. Farnesyl pyrophosphate synthase (FPS is a key enzyme of triterpenoids biosynthesis. The gene encoding FPS was cloned from P. cocos by degenerate PCR, inverse PCR and cassette PCR. The open reading frame of the gene is 1086 bp in length, corresponding to a predicted polypeptide of 361 amino acid residues with a molecular weight of 41.2 kDa. Comparison of the P. cocos FPS deduced amino acid sequence with other species showed the highest identity with Ganoderma lucidum (74%. The predicted P. cocos FPS shares at least four conserved regions involved in the enzymatic activity with the FPSs of varied species. The recombinant protein was expressed in Pichia pastoris and purified. Gas chromatography analysis showed that the recombinant FPS could catalyze the formation of farnesyl diphosphate (FPP from geranyl diphosphate (GPP and isopentenyl diphosphate (IPP. Furthermore, the expression profile of the FPS gene and content of total triterpenoids under different stages of development and methyl jasmonate treatments were determined. The results indicated that there is a positive correlation between the activity of FPS and the amount of total triterpenoids produced in P. cocos.

  4. Overexpression of Farnesyl Diphosphate Synthase in Arabidopsis Mitochondria Triggers Light-dependent Lesion Formation and Alters Cytokinin Homeostasis

    Czech Academy of Sciences Publication Activity Database

    Manzano, D.; Busquets, A.; Closa, M.; Hoyerová, Klára; Schaller, H.; Kamínek, Miroslav; Arró, M.; Ferrer, A.

    2006-01-01

    Roč. 61, 1-2 (2006), s. 195-213 ISSN 0167-4412 R&D Projects: GA AV ČR(CZ) IAA600380507 Institutional research plan: CEZ:AV0Z50380511 Keywords : Arabidopsis thaliana * cytokinin * farnesyl diphosphate synthase * isoprenoid Subject RIV: EF - Botanics Impact factor: 3.577, year: 2006

  5. Hibiscus cannabinus feruloyl-coa:monolignol transferase

    Science.gov (United States)

    Wilkerson, Curtis; Ralph, John; Withers, Saunia; Mansfield, Shawn D.

    2016-11-15

    The invention relates to isolated nucleic acids encoding a feruloyl-CoA:monolignol transferase and feruloyl-CoA:monolignol transferase enzymes. The isolated nucleic acids and/or the enzymes enable incorporation of monolignol ferulates into the lignin of plants, where such monolignol ferulates include, for example, p-coumaryl ferulate, coniferyl ferulate, and/or sinapyl ferulate. The invention also includes methods and plants that include nucleic acids encoding a feruloyl-CoA:monolignol transferase enzyme and/or feruloyl-CoA:monolignol transferase enzymes.

  6. Two pairs of farnesyl phenolic enantiomers as natural nitric oxide inhibitors from Ganoderma sinense.

    Science.gov (United States)

    Wang, Meng; Wang, Fei; Xu, Feng; Ding, Li-Qin; Zhang, Qian; Li, Hui-Xiang; Zhao, Feng; Wang, Li-Qing; Zhu, Li-Han; Chen, Li-Xia; Qiu, Feng

    2016-07-15

    Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26μM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Silymarin ameliorates metabolic dysfunction associated with Diet-induced Obesity via activation of farnesyl X receptor

    Directory of Open Access Journals (Sweden)

    Ming Gu

    2016-09-01

    Full Text Available AbstractBACKGROUND AND PURPOSESilymarin, a standardized extract of the milk thistle seeds, has been widely used to treat chronic hepatitis, cirrhosis and other types of toxic liver damage. . Despite increasing studies on the action of silymarin and its major active constituent, silybin in their therapeutic properties against insulin resistance, diabetes and hyperlipidaemia in vitro and in vivo, the mechanism underlying silymarin action remains unclear. EXPERIMENTAL APPROACHC57BL/6 mice were fed high-fat diet (HFD for 3 months to induce obesity, insulin resistance, hyperlipidaemia and fatty liver. These mice were then continuously treated with HFD alone or mixed with silymarin at 40 mg/100 g for additional 6 weeks. Biochemical analysis was used to test the serum lipid and bile acid profiles. FXR and NF-κB transactivities were analysed in liver using a gene reporter assay based onquantitative RT-PCR.KEY RESULTSSilymarin treatment ameliorated insulin resistance, dyslipidaemia and inflammation, and reconstituted the bile acid pool in liver of diet-induced obesity. Associated with this, silybin and silymarin enhanced FXR transactivity. Consistently, in HepG2 cells, silybin inhibited NF-κB signalling, which was enhanced by FXR activation. CONCLUSIONS AND IMPLICATIONSOur results suggest that silybin is an effective component of silymarin for treating metabolic syndrome by stimulating FXR signalling. Key words: silymarin; silybin; metabolic syndrome; non-alcoholic fatty liver disease; farnesyl X receptorAbbreviationsALT, alanine aminotransferase; AST, aspartate transaminase; BA, bile acid; DIO, diet-induced obesity; CA, cholic acid; DMSO, dimethylsulfoxide; FXR, farnesyl X receptor; HDL-c, high density lipoprotein cholesterol; HF, high-fat; IPITT, intraperitoneal insulin tolerance test; LDL-c, low density lipoprotein cholesterol; NAFLD, non-alcoholic fatty liver disease; NF-κB, nuclear factor kappa B; NR, nuclear receptor; MS, metabolic syndrome

  8. Inhibition of Coenzyme Qs Accumulation in Engineered Escherichia coli by High Concentration of Farnesyl Diphosphate

    Science.gov (United States)

    Samoudi, Mojtaba; Omid Yeganeh, Negar; Shahbani Zahiri, Hossein; Shariati, Parvin; Hajhosseini, Reza

    2015-01-01

    Background: Coenzyme Q 10 (CoQ 10 ) is an isoprenoid component used widely in nutraceutical industries. Farnesyl diphosphate synthase (FPPS) is a responsible enzyme for biosynthesis of farnesyl diphosphate (FPP), a key precursor for CoQs production. This research involved investigating the effect of FPPS over-expression on CoQs production in engineered CoQ 10 -producing Escherichia coli (E. coli). Methods: Two CoQ 10 -producing strains, as referred to E. coli Ba and E. coli Br, were transformed by the encoding gene for FPPS (ispA) under the control of either the trc or P BAD promoters. Results: Over-expression of ispA under the control of P BAD promoter led to a relative increase in CoQ 10 production only in recombinant E. coli Br although induction by arabinose resulted in partial reduction of CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains. Over-expression of ispA under the control of stronger trc promoter, however, led to a severe decrease in CoQ 10 production in both recombinant E. coli Ba and E. coli Br strains, as reflected by reductions from 629±40 to 30±13 and 564±28 to 80±14 μg/g Dried Cell Weight (DCW), respectively. The results showed high level of FPP reduces endogenous CoQ 8 production as well and that CoQs are produced in a complimentary manner, as the increase in production of one decreases the production of the other. Conclusion: The reduction in CoQ 10 production can be a result of Dds inhibition by high FPP concentration. Therefore, more effort is needed to verify the role of intermediate metabolite concentration and to optimize production of CoQ 10 . PMID:26306151

  9. Crystallographic and thermodynamic characterization of phenylaminopyridine bisphosphonates binding to human farnesyl pyrophosphate synthase.

    Directory of Open Access Journals (Sweden)

    Jaeok Park

    Full Text Available Human farnesyl pyrophosphate synthase (hFPPS catalyzes the production of the 15-carbon isoprenoid farnesyl pyrophosphate. The enzyme is a key regulator of the mevalonate pathway and a well-established drug target. Notably, it was elucidated as the molecular target of nitrogen-containing bisphosphonates, a class of drugs that have been widely successful against bone resorption disorders. More recently, research has focused on the anticancer effects of these inhibitors. In order to achieve increased non-skeletal tissue exposure, we created phenylaminopyridine bisphosphonates (PNP-BPs that have bulky hydrophobic side chains through a structure-based approach. Some of these compounds have proven to be more potent than the current clinical drugs in a number of antiproliferation assays using multiple myeloma cell lines. In the present work, we characterized the binding of our most potent PNP-BPs to the target enzyme, hFPPS. Co-crystal structures demonstrate that the molecular interactions designed to elicit tighter binding are indeed established. We carried out thermodynamic studies as well; the newly introduced protein-ligand interactions are clearly reflected in the enthalpy of binding measured, which is more favorable for the new PNP-BPs than for the lead compound. These studies also indicate that the affinity of the PNP-BPs to hFPPS is comparable to that of the current drug risedronate. Risedronate forms additional polar interactions via its hydroxyl functional group and thus exhibits more favorable binding enthalpy; however, the entropy of binding is more favorable for the PNP-BPs, owing to the greater desolvation effects resulting from their large hydrophobic side chains. These results therefore confirm the overall validity of our drug design strategy. With a distinctly different molecular scaffold, the PNP-BPs described in this report represent an interesting new group of future drug candidates. Further investigation should follow to

  10. Geranylgeranyl diphosphate synthase from Scoparia dulcis and Croton sublyratus. Plastid localization and conversion to a farnesyl diphosphate synthase by mutagenesis.

    Science.gov (United States)

    Sitthithaworn, W; Kojima, N; Viroonchatapan, E; Suh, D Y; Iwanami, N; Hayashi, T; Noji, M; Saito, K; Niwa, Y; Sankawa, U

    2001-02-01

    cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene-producing plants, Scoparia dulcis and Croton sublyratus, have been isolated using the homology-based polymerase chain reaction (PCR) method. Both clones contained highly conserved aspartate-rich motifs (DDXX(XX)D) and their N-terminal residues exhibited the characteristics of chloroplast targeting sequence. When expressed in Escherichia coli, both the full-length and truncated proteins in which the putative targeting sequence was deleted catalyzed the condensation of farnesyl diphosphate and isopentenyl diphosphate to produce geranylgeranyl diphosphate (GGPP). The structural factors determining the product length in plant GGPPSs were investigated by constructing S. dulcis GGPPS mutants on the basis of sequence comparison with the first aspartate-rich motif (FARM) of plant farnesyl diphosphate synthase. The result indicated that in plant GGPPSs small amino acids, Met and Ser, at the fourth and fifth positions before FARM and Pro and Cys insertion in FARM play essential roles in determination of product length. Further, when a chimeric gene comprised of the putative transit peptide of the S. dulcis GGPPS gene and a green fluorescent protein was introduced into Arabidopsis leaves by particle gun bombardment, the chimeric protein was localized in chloroplasts, indicating that the cloned S. dulcis GGPPS is a chloroplast protein.

  11. Identification of the S-transferase like superfamily bacillithiol transferases encoded by Bacillus subtilis

    Science.gov (United States)

    Perera, Varahenage R.; Lapek, John D.; Newton, Gerald L.; Gonzalez, David J.; Pogliano, Kit

    2018-01-01

    Bacillithiol is a low molecular weight thiol found in Firmicutes that is analogous to glutathione, which is absent in these bacteria. Bacillithiol transferases catalyze the transfer of bacillithiol to various substrates. The S-transferase-like (STL) superfamily contains over 30,000 putative members, including bacillithiol transferases. Proteins in this family are extremely divergent and are related by structural rather than sequence similarity, leaving it unclear if all share the same biochemical activity. Bacillus subtilis encodes eight predicted STL superfamily members, only one of which has been shown to be a bacillithiol transferase. Here we find that the seven remaining proteins show varying levels of metal dependent bacillithiol transferase activity. We have renamed the eight enzymes BstA-H. Mass spectrometry and gene expression studies revealed that all of the enzymes are produced to varying levels during growth and sporulation, with BstB and BstE being the most abundant and BstF and BstH being the least abundant. Interestingly, several bacillithiol transferases are induced in the mother cell during sporulation. A strain lacking all eight bacillithiol transferases showed normal growth in the presence of stressors that adversely affect growth of bacillithiol-deficient strains, such as paraquat and CdCl2. Thus, the STL bacillithiol transferases represent a new group of proteins that play currently unknown, but potentially significant roles in bacillithiol-dependent reactions. We conclude that these enzymes are highly divergent, perhaps to cope with an equally diverse array of endogenous or exogenous toxic metabolites and oxidants. PMID:29451913

  12. Structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate and two molecules of inorganic phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jaeok [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); Lin, Yih-Shyan [McGill University, 801 Rue Sherbrooke Ouest, Montreal, QC H3A 0B8 (Canada); Tsantrizos, Youla S. [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); McGill University, 801 Rue Sherbrooke Ouest, Montreal, QC H3A 0B8 (Canada); McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1 (Canada); Berghuis, Albert M., E-mail: albert.berghuis@mcgill.ca [McGill University, 3655 Promenade Sir William Osler, Montreal, QC H3G 1Y6 (Canada); McGill University, 3649 Promenade Sir William Osler, Montreal, QC H3G 0B1 (Canada); McGill University, 3775 Rue University, Montreal, QC H3A 2B4 (Canada)

    2014-02-19

    A co-crystal structure of human farnesyl pyrophosphate synthase in complex with an aminopyridine bisphosphonate, YS0470, and two molecules of inorganic phosphate has been determined. The identity of the phosphate ligands was confirmed by anomalous diffraction data. Human farnesyl pyrophosphate synthase (hFPPS) produces farnesyl pyrophos@@phate, an isoprenoid essential for a variety of cellular processes. The enzyme has been well established as the molecular target of the nitrogen-containing bisphosphonates (N-BPs), which are best known for their antiresorptive effects in bone but are also known for their anticancer properties. Crystal structures of hFPPS in ternary complexes with a novel bisphosphonate, YS0470, and the secondary ligands inorganic phosphate (P{sub i}), inorganic pyrophosphate (PP{sub i}) and isopentenyl pyrophosphate (IPP) have recently been reported. Only the co-binding of the bisphosphonate with either PP{sub i} or IPP resulted in the full closure of the C-@@terminal tail of the enzyme, a conformational change that is required for catalysis and that is also responsible for the potent in vivo efficacy of N-BPs. In the present communication, a co-crystal structure of hFPPS in complex with YS0470 and two molecules of P{sub i} is reported. The unusually close proximity between these ligands, which was confirmed by anomalous diffraction data, suggests that they interact with one another, with their anionic charges neutralized in their bound state. The structure also showed the tail of the enzyme to be fully disordered, indicating that simultaneous binding of two P{sub i} molecules with a bisphosphonate cannot induce the tail-closing conformational change in hFPPS. Examination of homologous FPPSs suggested that this ligand-dependent tail closure is only conserved in the mammalian proteins. The prevalence of P{sub i}-bound hFPPS structures in the PDB raises a question regarding the in vivo relevance of P{sub i} binding to the function of the enzyme.

  13. Engineered protein degradation of farnesyl pyrophosphate synthase is an effective regulatory mechanism to increase monoterpene production in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Peng, Bingyin; Nielsen, Lars K.; Kampranis, Sotirios C

    2018-01-01

    Monoterpene production in Saccharomyces cerevisae requires the introduction of heterologous monoterpene synthases (MTSs). The endogenous farnesyl pyrosphosphate synthase (FPPS; Erg20p) competes with MTSs for the precursor geranyl pyrophosphate (GPP), which limits the production of monoterpenes. ERG......20 is an essential gene that cannot be deleted and transcriptional down-regulation of ERG20 has failed to improve monoterpene production. Here, we investigated an N-degron-dependent protein degradation strategy to down-regulate Erg20p activity. Degron tagging decreased GFP protein half......-life drastically to 1 h (degron K3K15) or 15 min (degrons KN113 and KN119). Degron tagging of ERG20 was therefore paired with a sterol responsive promoter to ensure sufficient metabolic flux to essential downstream sterols despite the severe destabilisation effect of degron tagging. A dual monoterpene...

  14. Structural and thermodynamic basis of the inhibition of Leishmania major farnesyl diphosphate synthase by nitrogen-containing bisphosphonates

    Energy Technology Data Exchange (ETDEWEB)

    Aripirala, Srinivas [Johns Hopkins University, 725 North Wolfe Street WBSB 605, Baltimore, MD 21210 (United States); Gonzalez-Pacanowska, Dolores [López-Neyra Institute of Parasitology and Biomedicine, 18001 Granada (Spain); Oldfield, Eric [University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States); Kaiser, Marcel [University of Basel, Petersplatz 1, CH-4003 Basel (Switzerland); Amzel, L. Mario, E-mail: mamzel@jhmi.edu [Johns Hopkins University School of Medicine, 725 N. Wolfe Street WBSB 604, Baltimore, MD 21205 (United States); Gabelli, Sandra B., E-mail: mamzel@jhmi.edu [Johns Hopkins University School of Medicine, 725 N. Wolfe Street WBSB 604, Baltimore, MD 21205 (United States); Johns Hopkins University School of Medicine, Baltimore, MD 21205 (United States); Johns Hopkins University, 725 North Wolfe Street WBSB 605, Baltimore, MD 21210 (United States)

    2014-03-01

    Structural insights into L. major farnesyl diphosphate synthase, a key enzyme in the mevalonate pathway, are described. Farnesyl diphosphate synthase (FPPS) is an essential enzyme involved in the biosynthesis of sterols (cholesterol in humans and ergosterol in yeasts, fungi and trypanosomatid parasites) as well as in protein prenylation. It is inhibited by bisphosphonates, a class of drugs used in humans to treat diverse bone-related diseases. The development of bisphosphonates as antiparasitic compounds targeting ergosterol biosynthesis has become an important route for therapeutic intervention. Here, the X-ray crystallographic structures of complexes of FPPS from Leishmania major (the causative agent of cutaneous leishmaniasis) with three bisphosphonates determined at resolutions of 1.8, 1.9 and 2.3 Å are reported. Two of the inhibitors, 1-(2-hydroxy-2,2-diphosphonoethyl)-3-phenylpyridinium (300B) and 3-butyl-1-(2,2-diphosphonoethyl)pyridinium (476A), co-crystallize with the homoallylic substrate isopentenyl diphosphate (IPP) and three Ca{sup 2+} ions. A third inhibitor, 3-fluoro-1-(2-hydroxy-2,2-diphosphonoethyl)pyridinium (46I), was found to bind two Mg{sup 2+} ions but not IPP. Calorimetric studies showed that binding of the inhibitors is entropically driven. Comparison of the structures of L. major FPPS (LmFPPS) and human FPPS provides new information for the design of bisphosphonates that will be more specific for inhibition of LmFPPS. The asymmetric structure of the LmFPPS–46I homodimer indicates that binding of the allylic substrate to both monomers of the dimer results in an asymmetric dimer with one open and one closed homoallylic site. It is proposed that IPP first binds to the open site, which then closes, opening the site on the other monomer, which closes after binding the second IPP, leading to the symmetric fully occupied FPPS dimer observed in other structures.

  15. Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses.

    Science.gov (United States)

    Manzano, David; Andrade, Paola; Caudepón, Daniel; Altabella, Teresa; Arró, Montserrat; Ferrer, Albert

    2016-09-01

    Farnesyl diphosphate synthase (FPS) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. Arabidopsis (Arabidopsis thaliana) contains two genes (FPS1 and FPS2) encoding FPS. Single fps1 and fps2 knockout mutants are phenotypically indistinguishable from wild-type plants, while fps1/fps2 double mutants are embryo lethal. To assess the effect of FPS down-regulation at postembryonic developmental stages, we generated Arabidopsis conditional knockdown mutants expressing artificial microRNAs devised to simultaneously silence both FPS genes. Induction of silencing from germination rapidly caused chlorosis and a strong developmental phenotype that led to seedling lethality. However, silencing of FPS after seed germination resulted in a slight developmental delay only, although leaves and cotyledons continued to show chlorosis and altered chloroplasts. Metabolomic analyses also revealed drastic changes in the profile of sterols, ubiquinones, and plastidial isoprenoids. RNA sequencing and reverse transcription-quantitative polymerase chain reaction transcriptomic analysis showed that a reduction in FPS activity levels triggers the misregulation of genes involved in biotic and abiotic stress responses, the most prominent one being the rapid induction of a set of genes related to the jasmonic acid pathway. Down-regulation of FPS also triggered an iron-deficiency transcriptional response that is consistent with the iron-deficient phenotype observed in FPS-silenced plants. The specific inhibition of the sterol biosynthesis pathway by chemical and genetic blockage mimicked these transcriptional responses, indicating that sterol depletion is the primary cause of the observed alterations. Our results highlight the importance of sterol homeostasis for normal chloroplast development and function and reveal important clues about how isoprenoid and sterol metabolism is integrated within plant physiology and development. © 2016

  16. SIKLODEKSTRIN GLIKOSIL TRANSFERASE DAN PEMANFAATANNYA DALAM INDUSTRI [Cyclodextrin Glycosyl Transferase and its application in industries

    Directory of Open Access Journals (Sweden)

    Budiasih Wahyuntari

    2005-12-01

    Full Text Available Cyclodextrin glycosyl transferase (CGT-ase is mainly produced by Bacilli. Systematical name of the enzyme is E.C. 2.4.1.19 a-1,4 glucan-4-glycosyl transferase. The enzyme catalyzes hydrolysis of starch intramolecular, and intermolecular transglycosylation of a-1,4, glucan chains. Cyclodextrins are a-1,4 linked cyclic oligosaccharides resulting from enzymatic degradation of starch by cyclodextrin glycosyl transferase through untramolecular transglycosylation. The major cyclodextrins are made up of 6, 7 and 8 glucopyranose units which are known as a-, b-, and y-cyclodextrin. All CGT-ase catalyze three kinds of cyclodextrins, the proportion of the cyclodextrins depends on the enzyme source and reaction conditions. The intermolecular transglycosylation ability of the enzyme has been applied in transfering glycosyl residues into suitable acceptor. Transglycosylation by the enzymes have been tested to improve solubility of some flavonoids and to favor precipitation ci some glycosides.

  17. Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas

    DEFF Research Database (Denmark)

    Mandel, U; Hassan, H; Therkildsen, M H

    1999-01-01

    GalNAc-T1, -T2, and -T3. Application of this panel of novel antibodies revealed that GalNAc- transferases are differentially expressed in different cell lines, in spermatozoa, and in oral mucosa and carcinomas. For example, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, and Gal......NAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa. The expression patterns in normal oral mucosa were found to vary with cell differentiation, and for GalNAc-T2 and -T3 this was reflected in oral squamous cell carcinomas. The expression pattern of GalNAc-T1 was on the other hand changed...

  18. Genomic organization of plant aminopropyl transferases.

    Science.gov (United States)

    Rodríguez-Kessler, Margarita; Delgado-Sánchez, Pablo; Rodríguez-Kessler, Gabriela Theresia; Moriguchi, Takaya; Jiménez-Bremont, Juan Francisco

    2010-07-01

    Aminopropyl transferases like spermidine synthase (SPDS; EC 2.5.1.16), spermine synthase and thermospermine synthase (SPMS, tSPMS; EC 2.5.1.22) belong to a class of widely distributed enzymes that use decarboxylated S-adenosylmethionine as an aminopropyl donor and putrescine or spermidine as an amino acceptor to form in that order spermidine, spermine or thermospermine. We describe the analysis of plant genomic sequences encoding SPDS, SPMS, tSPMS and PMT (putrescine N-methyltransferase; EC 2.1.1.53). Genome organization (including exon size, gain and loss, as well as intron number, size, loss, retention, placement and phase, and the presence of transposons) of plant aminopropyl transferase genes were compared between the genomic sequences of SPDS, SPMS and tSPMS from Zea mays, Oryza sativa, Malus x domestica, Populus trichocarpa, Arabidopsis thaliana and Physcomitrella patens. In addition, the genomic organization of plant PMT genes, proposed to be derived from SPDS during the evolution of alkaloid metabolism, is illustrated. Herein, a particular conservation and arrangement of exon and intron sequences between plant SPDS, SPMS and PMT genes that clearly differs with that of ACL5 genes, is shown. The possible acquisition of the plant SPMS exon II and, in particular exon XI in the monocot SPMS genes, is a remarkable feature that allows their differentiation from SPDS genes. In accordance with our in silico analysis, functional complementation experiments of the maize ZmSPMS1 enzyme (previously considered to be SPDS) in yeast demonstrated its spermine synthase activity. Another significant aspect is the conservation of intron sequences among SPDS and PMT paralogs. In addition the existence of microsynteny among some SPDS paralogs, especially in P. trichocarpa and A. thaliana, supports duplication events of plant SPDS genes. Based in our analysis, we hypothesize that SPMS genes appeared with the divergence of vascular plants by a processes of gene duplication and the

  19. The Genetic Architecture of Murine Glutathione Transferases.

    Directory of Open Access Journals (Sweden)

    Lu Lu

    Full Text Available Glutathione S-transferase (GST genes play a protective role against oxidative stress and may influence disease risk and drug pharmacokinetics. In this study, massive multiscalar trait profiling across a large population of mice derived from a cross between C57BL/6J (B6 and DBA2/J (D2--the BXD family--was combined with linkage and bioinformatic analyses to characterize mechanisms controlling GST expression and to identify downstream consequences of this variation. Similar to humans, mice show a wide range in expression of GST family members. Variation in the expression of Gsta4, Gstt2, Gstz1, Gsto1, and Mgst3 is modulated by local expression QTLs (eQTLs in several tissues. Higher expression of Gsto1 in brain and liver of BXD strains is strongly associated (P < 0.01 with inheritance of the B6 parental allele whereas higher expression of Gsta4 and Mgst3 in brain and liver, and Gstt2 and Gstz1 in brain is strongly associated with inheritance of the D2 parental allele. Allele-specific assays confirmed that expression of Gsto1, Gsta4, and Mgst3 are modulated by sequence variants within or near each gene locus. We exploited this endogenous variation to identify coexpression networks and downstream targets in mouse and human. Through a combined systems genetics approach, we provide new insight into the biological role of naturally occurring variants in GST genes.

  20. Glutathione transferase mimics : Micellar catalysis of an enzymic reaction

    NARCIS (Netherlands)

    Lindkvist, Björn; Weinander, Rolf; Engman, Lars; Koetse, Marc; Engberts, Jan B.F.N.; Morgenstern, Ralf

    1997-01-01

    Substances that mimic the enzyme action of glutathione transferases (which serve in detoxification) are described. These micellar catalysts enhance the reaction rate between thiols and activated halogenated nitroarenes as well as alpha,beta-unsaturated carbonyls. The nucleophilic aromatic

  1. The association between glutathione S-transferase P1 ...

    African Journals Online (AJOL)

    Mahmoud I. Mahmoud

    2011-08-10

    Aug 10, 2011 ... B-adrenergic receptor polymorphisms and response to salmeterol. Am J Respir Crit Care ... transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis 1997;18(4):641–4.

  2. Synthesis of a tritium labeled photolabile analogue of farnesyl diphosphate: (E,E)-[1-3H]-(2-diazo-3-trifluoropropionyloxy)geranyl diphosphate (DATFP-GDP)

    International Nuclear Information System (INIS)

    Liu, J.; Benedict, C.R.

    1996-01-01

    Tritiated (E,E)-(2-diazo-3-trifluoropropionyloxy)geranyl disphosphate (DATFP-GDP) has been used as a photolabile analogue of (E,E)-farnesyl diphosphate (E,E-FDP) for an aid in isolating enzymes utilizing E,E-FDP as a substrate. We now report an alternative method of synthesizing this probe in which the tritium label is introduced in the step just before the introduction of the diphospate group. Thus, DATFP-geranial is oxidized to DATFP-geranial with activated manganese dioxide. The tritium label is introduced by reduction of the aldehyde with NaBT 4 . The DATFP-group successfully withstands both of these steps. The overall yield for these two steps is 69%. Diphosphorylation of the resulting alcohol afforded DATFP-[1- 3 H]-GDP in 8% yield with a specific activity of 48.6 μCi/μmol and radiochemical purity of 94%. (Author)

  3. Molecular cloning and expression of Chimonanthus praecox farnesyl pyrophosphate synthase gene and its possible involvement in the biosynthesis of floral volatile sesquiterpenoids.

    Science.gov (United States)

    Xiang, Lin; Zhao, Kaige; Chen, Longqing

    2010-01-01

    Farnesyl pyrophosphate (FPP) synthase catalyzes the biosynthesis of FPP, which is the precursors of sesquiterpenoids such as floral scent volatiles, from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). cDNA encoding wintersweet (Chimonanthus praecox L.) FPP synthase was isolated by the RT-PCR and RACE methods. The deduced amino acid sequence showed a high identity to plant FPP synthases. Expression of the gene in Escherichia coli yielded FPPS activity that catalyzed the synthesis of FPP as a main product. Tissue-specific and developmental analyses of the mRNA levels of CpFPPS and volatile sesquiterpenoids levels in C. praecox flowers revealed that the FPPS may play a regulatory role in floral volatile sesquiterpenoids of wintersweet. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  4. Homogentisate solanesyl transferase (HST) cDNA’s in maize

    Science.gov (United States)

    Maize white seedling 3 (w3) has served as a model albino-seedling mutant since its discovery in 1923. We show that the w3 phenotype is caused by disruptions in homogentisate solanesyl transferase (HST), an enzyme that catalyzes the committed step in plastoquinone-9 (PQ9) biosynthesis. This reaction ...

  5. Insecticide resistance and glutathione S-transferases in mosquitoes ...

    African Journals Online (AJOL)

    Mosquito glutathione S-transferases (GSTs) have received considerable attention in the last 20 years because of their role in insecticide metabolism producing resistance. Many different compounds, including toxic xenobiotics and reactive products of intracellular processes such as lipid peroxidation, act as GST substrates.

  6. Steroid sulfatase and sulfuryl transferase activities in human brain tumors

    Czech Academy of Sciences Publication Activity Database

    Kříž, L.; Bičíková, M.; Mohapl, M.; Hill, M.; Černý, Ivan; Hampl, R.

    2008-01-01

    Roč. 109, č. 1 (2008), s. 31-39 ISSN 0960-0760 Institutional research plan: CEZ:AV0Z40550506 Keywords : dehydroepiandrosterone * steroid sulfatase * steroid sulfuryl transferase * brain Subject RIV: CC - Organic Chemistry Impact factor: 2.827, year: 2008

  7. Enzymatic synthesis of farnesyl laurate in organic solvent: initial water activity, kinetics mechanism, optimization of continuous operation using packed bed reactor and mass transfer studies.

    Science.gov (United States)

    Rahman, N K; Kamaruddin, A H; Uzir, M H

    2011-08-01

    The influence of water activity and water content was investigated with farnesyl laurate synthesis catalyzed by Lipozyme RM IM. Lipozyme RM IM activity depended strongly on initial water activity value. The best results were achieved for a reaction medium with an initial water activity of 0.11 since it gives the best conversion value of 96.80%. The rate constants obtained in the kinetics study using Ping-Pong-Bi-Bi and Ordered-Bi-Bi mechanisms with dead-end complex inhibition of lauric acid were compared. The corresponding parameters were found to obey the Ordered-Bi-Bi mechanism with dead-end complex inhibition of lauric acid. Kinetic parameters were calculated based on this model as follows: V (max) = 5.80 mmol l(-1) min(-1) g enzyme(-1), K (m,A) = 0.70 mmol l(-1) g enzyme(-1), K (m,B) = 115.48 mmol l(-1) g enzyme(-1), K (i) = 11.25 mmol l(-1) g enzyme(-1). The optimum conditions for the esterification of farnesol with lauric acid in a continuous packed bed reactor were found as the following: 18.18 cm packed bed height and 0.9 ml/min substrate flow rate. The optimum molar conversion of lauric acid to farnesyl laurate was 98.07 ± 0.82%. The effect of mass transfer in the packed bed reactor has also been studied using two models for cases of reaction limited and mass transfer limited. A very good agreement between the mass transfer limited model and the experimental data obtained indicating that the esterification in a packed bed reactor was mass transfer limited.

  8. Geranylgeranyl diphosphate synthase in fission yeast is a heteromer of farnesyl diphosphate synthase (FPS), Fps1, and an FPS-like protein, Spo9, essential for sporulation.

    Science.gov (United States)

    Ye, Yanfang; Fujii, Makoto; Hirata, Aiko; Kawamukai, Makoto; Shimoda, Chikashi; Nakamura, Taro

    2007-09-01

    Both farnesyl diphosphate synthase (FPS) and geranylgeranyl diphosphate synthase (GGPS) are key enzymes in the synthesis of various isoprenoid-containing compounds and proteins. Here, we describe two novel Schizosaccharomyces pombe genes, fps1(+) and spo9(+), whose products are similar to FPS in primary structure, but whose functions differ from one another. Fps1 is essential for vegetative growth, whereas, a spo9 null mutant exhibits temperature-sensitive growth. Expression of fps1(+), but not spo9(+), suppresses the lethality of a Saccharomyces cerevisiae FPS-deficient mutant and also restores ubiquinone synthesis in an Escherichia coli ispA mutant, which lacks FPS activity, indicating that S. pombe Fps1 in fact functions as an FPS. In contrast to a typical FPS gene, no apparent GGPS homologues have been found in the S. pombe genome. Interestingly, although neither fps1(+) nor spo9(+) expression alone in E. coli confers clear GGPS activity, coexpression of both genes induces such activity. Moreover, the GGPS activity is significantly reduced in the spo9 mutant. In addition, the spo9 mutation perturbs the membrane association of a geranylgeranylated protein, but not that of a farnesylated protein. Yeast two-hybrid and coimmunoprecipitation analyses indicate that Fps1 and Spo9 physically interact. Thus, neither Fps1 nor Spo9 alone functions as a GGPS, but the two proteins together form a complex with GGPS activity. Because spo9 was originally identified as a sporulation-deficient mutant, we show here that expansion of the forespore membrane is severely inhibited in spo9Delta cells. Electron microscopy revealed significant accumulation membrane vesicles in spo9Delta cells. We suggest that lack of GGPS activity in a spo9 mutant results in impaired protein prenylation in certain proteins responsible for secretory function, thereby inhibiting forespore membrane formation.

  9. Suppressing Farnesyl Diphosphate Synthase Alters Chloroplast Development and Triggers Sterol-Dependent Induction of Jasmonate- and Fe-Related Responses1[OPEN

    Science.gov (United States)

    Andrade, Paola; Caudepón, Daniel; Arró, Montserrat

    2016-01-01

    Farnesyl diphosphate synthase (FPS) catalyzes the synthesis of farnesyl diphosphate from isopentenyl diphosphate and dimethylallyl diphosphate. Arabidopsis (Arabidopsis thaliana) contains two genes (FPS1 and FPS2) encoding FPS. Single fps1 and fps2 knockout mutants are phenotypically indistinguishable from wild-type plants, while fps1/fps2 double mutants are embryo lethal. To assess the effect of FPS down-regulation at postembryonic developmental stages, we generated Arabidopsis conditional knockdown mutants expressing artificial microRNAs devised to simultaneously silence both FPS genes. Induction of silencing from germination rapidly caused chlorosis and a strong developmental phenotype that led to seedling lethality. However, silencing of FPS after seed germination resulted in a slight developmental delay only, although leaves and cotyledons continued to show chlorosis and altered chloroplasts. Metabolomic analyses also revealed drastic changes in the profile of sterols, ubiquinones, and plastidial isoprenoids. RNA sequencing and reverse transcription-quantitative polymerase chain reaction transcriptomic analysis showed that a reduction in FPS activity levels triggers the misregulation of genes involved in biotic and abiotic stress responses, the most prominent one being the rapid induction of a set of genes related to the jasmonic acid pathway. Down-regulation of FPS also triggered an iron-deficiency transcriptional response that is consistent with the iron-deficient phenotype observed in FPS-silenced plants. The specific inhibition of the sterol biosynthesis pathway by chemical and genetic blockage mimicked these transcriptional responses, indicating that sterol depletion is the primary cause of the observed alterations. Our results highlight the importance of sterol homeostasis for normal chloroplast development and function and reveal important clues about how isoprenoid and sterol metabolism is integrated within plant physiology and development. PMID

  10. 21 CFR 862.1030 - Alanine amino transferase (ALT/SGPT) test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alanine amino transferase (ALT/SGPT) test system... Test Systems § 862.1030 Alanine amino transferase (ALT/SGPT) test system. (a) Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended to measure the activity of the...

  11. Strengthening Triterpene Saponins Biosynthesis by Over-Expression of Farnesyl Pyrophosphate Synthase Gene and RNA Interference of Cycloartenol Synthase Gene in Panax notoginseng Cells

    Directory of Open Access Journals (Sweden)

    Yan Yang

    2017-04-01

    Full Text Available To conform to the multiple regulations of triterpene biosynthesis, the gene encoding farnesyl pyrophosphate synthase (FPS was transformed into Panax notoginseng (P. notoginseng cells in which RNA interference (RNAi of the cycloartenol synthase (CAS gene had been accomplished. Transgenic cell lines showed both higher expression levels of FPS and lower expression levels of CAS compared to the wild-type (WT cells. In the triterpene and phytosterol analysis, transgenic cell lines provided a higher accumulation of total triterpene saponins, and a lower amount of phytosterols in comparison with the WT cells. Compared with the cells in which RNAi of the CAS gene was achieved, the cells with simultaneously over-expressed FPS and silenced CAS showed higher triterpene contents. These results demonstrate that over-expression of FPS can break the rate-limiting reaction catalyzed by FPS in the triterpene saponins biosynthetic pathway; and inhibition of CAS expression can decrease the synthesis metabolic flux of the phytosterol branch. Thus, more precursors flow in the direction of triterpene synthesis, and ultimately promote the accumulation of P. notoginseng saponins. Meanwhile, silencing and over-expressing key enzyme genes simultaneously is more effective than just manipulating one gene in the regulation of saponin biosynthesis.

  12. Geranylgeranyl diphosphate synthases from Scoparia dulcis and Croton sublyratus. cDNA cloning, functional expression, and conversion to a farnesyl diphosphate synthase.

    Science.gov (United States)

    Kojima, N; Sitthithaworn, W; Viroonchatapan, E; Suh, D Y; Iwanami, N; Hayashi, T; Sankaw, U

    2000-07-01

    cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene producing plants, Scoparia dulcis and Croton sublyratus, were isolated using the homology-based polymerase chain reaction method. Both cloned genes showed high amino acid sequence homology (60-70%) to other plant GGPPSs and contained highly conserved aspartate-rich motifs. The obtained clones were functionally expressed in Escherichia coli and showed sufficient GGPPS activity to catalyze the condensation of farnesyl diphosphate (FPP) and isopentenyl diphosphate to form geranylgeranyl diphosphate. To investigate the factor determining the product chain length of plant GGPPSs, S. dulcis GGPPS mutants in which either the small amino acids at the fourth and fifth positions before the first aspartate-rich motif (FARM) were replaced with aromatic amino acids or in which two additional amino acids in FARM were deleted were constructed. Both mutants behaved like FPPS-like enzymes and almost exclusively produced FPP when dimethylallyl diphosphate was used as a primer substrate, and failed to accept FPP as a primer substrate. These results indicate that both small amino acids at the fourth and fifth positions before FARM and the amino acid insertion in FARM play essential roles in product length determination in plant GGPPSs.

  13. Interaction of pleuromutilin derivatives with the ribosomal peptidyl transferase center

    DEFF Research Database (Denmark)

    Long, K. S.; Hansen, L. K.; Jakobsen, L.

    2006-01-01

    Tiamulin is a pleuromutilin antibiotic that is used in veterinary medicine. The recently published crystal structure of a tiamulin-50S ribosomal subunit complex provides detailed information about how this drug targets the peptidyl transferase center of the ribosome. To promote rational design...... mutant strain is resistant to tiamulin and pleuromutilin, but not valnemulin, implying that valnemulin is better able to withstand an altered rRNA binding surface around the mutilin core. This is likely due to additional interactions made between the valnemulin side chain extension and the rRNA binding...

  14. A glutathione s-transferase confers herbicide tolerance in rice

    Directory of Open Access Journals (Sweden)

    Tingzhang Hu

    2014-07-01

    Full Text Available Plant glutathione S-transferases (GSTs have been a focus of attention due to their role in herbicide detoxification. OsGSTL2 is a glutathione S-transferase, lambda class gene from rice (Oryza sativa L.. Transgenic rice plants over-expressing OsGSTL2 were generated from rice calli by the use of an Agrobacterium transformation system, and were screened by a combination of hygromycin resistance, PCR and Southern blot analysis. In the vegetative tissues of transgenic rice plants, the over-expression of OsGSTL2 not only increased levels of OsGSTL2 transcripts, but also GST and GPX expression, while reduced superoxide. Transgenic rice plants also showed higher tolerance to glyphosate and chlorsulfuron, which often contaminate agricultural fields. The findings demonstrate the detoxification role of OsGSTL2 in the growth and development of rice plants. It should be possible to apply the present results to crops for developing herbicide tolerance and for limiting herbicide contamination in the food chain.

  15. Interaction of Pleuromutilin Derivatives with the Ribosomal Peptidyl Transferase Center

    Science.gov (United States)

    Long, Katherine S.; Hansen, Lykke H.; Jakobsen, Lene; Vester, Birte

    2006-01-01

    Tiamulin is a pleuromutilin antibiotic that is used in veterinary medicine. The recently published crystal structure of a tiamulin-50S ribosomal subunit complex provides detailed information about how this drug targets the peptidyl transferase center of the ribosome. To promote rational design of pleuromutilin-based drugs, the binding of the antibiotic pleuromutilin and three semisynthetic derivatives with different side chain extensions has been investigated using chemical footprinting. The nucleotides A2058, A2059, G2505, and U2506 are affected in all of the footprints, suggesting that the drugs are similarly anchored in the binding pocket by the common tricyclic mutilin core. However, varying effects are observed at U2584 and U2585, indicating that the side chain extensions adopt distinct conformations within the cavity and thereby affect the rRNA conformation differently. An Escherichia coli L3 mutant strain is resistant to tiamulin and pleuromutilin, but not valnemulin, implying that valnemulin is better able to withstand an altered rRNA binding surface around the mutilin core. This is likely due to additional interactions made between the valnemulin side chain extension and the rRNA binding site. The data suggest that pleuromutilin drugs with enhanced antimicrobial activity may be obtained by maximizing the number of interactions between the side chain moiety and the peptidyl transferase cavity. PMID:16569865

  16. A novel method for screening the glutathione transferase inhibitors

    Directory of Open Access Journals (Sweden)

    Węgrzyn Grzegorz

    2009-03-01

    Full Text Available Abstract Background Glutathione transferases (GSTs belong to the family of Phase II detoxification enzymes. GSTs catalyze the conjugation of glutathione to different endogenous and exogenous electrophilic compounds. Over-expression of GSTs was demonstrated in a number of different human cancer cells. It has been found that the resistance to many anticancer chemotherapeutics is directly correlated with the over-expression of GSTs. Therefore, it appears to be important to find new GST inhibitors to prevent the resistance of cells to anticancer drugs. In order to search for glutathione transferase (GST inhibitors, a novel method was designed. Results Our results showed that two fragments of GST, named F1 peptide (GYWKIKGLV and F2 peptide (KWRNKKFELGLEFPNL, can significantly inhibit the GST activity. When these two fragments were compared with several known potent GST inhibitors, the order of inhibition efficiency (measured in reactions with 2,4-dinitrochlorobenzene (CDNB and glutathione as substrates was determined as follows: tannic acid > cibacron blue > F2 peptide > hematin > F1 peptide > ethacrynic acid. Moreover, the F1 peptide appeared to be a noncompetitive inhibitor of the GST-catalyzed reaction, while the F2 peptide was determined as a competitive inhibitor of this reaction. Conclusion It appears that the F2 peptide can be used as a new potent specific GST inhibitor. It is proposed that the novel method, described in this report, might be useful for screening the inhibitors of not only GST but also other enzymes.

  17. Acrolein-detoxifying isozymes of glutathione transferase in plants.

    Science.gov (United States)

    Mano, Jun'ichi; Ishibashi, Asami; Muneuchi, Hitoshi; Morita, Chihiro; Sakai, Hiroki; Biswas, Md Sanaullah; Koeduka, Takao; Kitajima, Sakihito

    2017-02-01

    Acrolein is a lipid-derived highly reactive aldehyde, mediating oxidative signal and damage in plants. We found acrolein-scavenging glutathione transferase activity in plants and purified a low K M isozyme from spinach. Various environmental stressors on plants cause the generation of acrolein, a highly toxic aldehyde produced from lipid peroxides, via the promotion of the formation of reactive oxygen species, which oxidize membrane lipids. In mammals, acrolein is scavenged by glutathione transferase (GST; EC 2.5.1.18) isozymes of Alpha, Pi, and Mu classes, but plants lack these GST classes. We detected the acrolein-scavenging GST activity in four species of plants, and purified an isozyme showing this activity from spinach (Spinacia oleracea L.) leaves. The isozyme (GST-Acr), obtained after an affinity chromatography and two ion exchange chromatography steps, showed the K M value for acrolein 93 μM, the smallest value known for acrolein-detoxifying enzymes in plants. Peptide sequence homology search revealed that GST-Acr belongs to the GST Tau, a plant-specific class. The Arabidopsis thaliana GST Tau19, which has the closest sequence similar to spinach GST-Acr, also showed a high catalytic efficiency for acrolein. These results suggest that GST plays as a scavenger for acrolein in plants.

  18. Oral Cancer

    Science.gov (United States)

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  19. N-Acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191): an anti-inflammatory molecule that increases the expression of the aquaglyceroporin, aquaporin-3, in human keratinocytes.

    Science.gov (United States)

    Fernández, José R; Webb, Corey; Rouzard, Karl; Voronkov, Michael; Huber, Kristen L; Stock, Jeffry B; Stock, Maxwell; Gordon, Joel S; Perez, Eduardo

    2017-03-01

    Isoprenylcysteine (IPC) small molecules were discovered as signal transduction modulating compounds ~25 years ago. More recently, IPC molecules have demonstrated antioxidant and anti-inflammatory properties in a variety of dermal cells as well as antimicrobial activity, representing a novel class of compounds to ameliorate skin conditions and disease. Here, we demonstrate a new IPC compound, N-acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191), which inhibits UVB-induced inflammation blocking pro-inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production. To investigate further the previously reported hydrating potential of IPC compounds, SIG-1191 was tested for its ability to modulate aquaporin expression. Specifically, aquaporin 3 (AQP3) the most abundant aquaporin found in skin has been reported to play a key role in skin hydration, elasticity and barrier repair. Results show here for the first time that SIG-1191 increases AQP3 expression in both cultured normal human epidermal keratinocytes as well as when applied topically in a three-dimensional (3D) reconstructed human skin equivalent. Additionally, SIG-1191 dose dependently increased AQP3 protein levels, as determined by specific antibody staining, in the epidermis of the 3D skin equivalents. To begin to elucidate which signaling pathways SIG-1191 may be modulating to increase AQP3 levels, we used several pharmacological pathway inhibitors and determined that AQP3 expression is mediated by the Mitogen-activated protein kinase/Extracellular signal-regulated kinase kinase (MEK) pathway. Altogether, these data suggest SIG-1191 represents a new IPC derivative with anti-inflammatory activity that may also promote increased skin hydration based on its ability to increase AQP3 levels.

  20. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  1. From glutathione transferase to pore in a CLIC

    CERN Document Server

    Cromer, B A; Morton, C J; Parker, M W; 10.1007/s00249-002-0219-1

    2002-01-01

    Many plasma membrane chloride channels have been cloned and characterized in great detail. In contrast, very little is known about intracellular chloride channels. Members of a novel class of such channels, called the CLICs (chloride intracellular channels), have been identified over the last few years. A striking feature of the CLIC family of ion channels is that they can exist in a water- soluble state as well as a membrane-bound state. A major step forward in understanding the functioning of these channels has been the recent crystal structure determination of one family member, CLIC1. The structure confirms that CLICs are members of the glutathione S- transferase superfamily and provides clues as to how CLICs can insert into membranes to form chloride channels. (69 refs).

  2. Functional analysis and localisation of a delta-class glutathione S-transferase from Sarcoptes scabiei.

    Science.gov (United States)

    Pettersson, Eva U; Ljunggren, Erland L; Morrison, David A; Mattsson, Jens G

    2005-01-01

    The mite Sarcoptes scabiei causes sarcoptic mange, or scabies, a disease that affects both animals and humans worldwide. Our interest in S. scabiei led us to further characterise a glutathione S-transferase. This multifunctional enzyme is a target for vaccine and drug development in several parasitic diseases. The S. scabiei glutathione S-transferase open reading frame reported here is 684 nucleotides long and yields a protein with a predicted molecular mass of 26 kDa. Through phylogenetic analysis the enzyme was classified as a delta-class glutathione S-transferase, and our paper is the first to report that delta-class glutathione S-transferases occur in organisms other than insects. The recombinant S. scabiei glutathione S-transferase was expressed in Escherichia coli via three different constructs and purified for biochemical analysis. The S. scabiei glutathione S-transferase was active towards the substrate 1-chloro-2,4-dinitrobenzene, though the positioning of fusion partners influenced the kinetic activity of the enzyme. Polyclonal antibodies raised against S. scabiei glutathione S-transferase specifically localised the enzyme to the integument of the epidermis and cavities surrounding internal organs in adult parasites. However, some minor staining of parasite intestines was observed. No staining was seen in host tissues, nor could we detect any antibody response against S. scabiei glutathione S-transferase in sera from naturally S. scabiei infected dogs or pigs. Additionally, the polyclonal sera raised against recombinant S. scabiei glutathione S-transferase readily detected a protein from mites, corresponding to the predicted size of native glutathione S-transferase.

  3. Molecular basis for the presence of glycosylated onco-foetal fibronectin in oral carcinomas

    DEFF Research Database (Denmark)

    Wandall, Hans H; Dabelsteen, Sally; Sørensen, Jens Ahm

    2007-01-01

    spliced IIICS region. Using cell culture experiments, immunohistochemical staining of primary tissue, and RT-PCR of tumour cells isolated by laser capture techniques we have examined the molecular basis for the production of GOF in oral carcinomas. Immuno-histochemical investigation confirmed the stromal......Glycosylated onco-foetal fibronectin (GOF) deposited in the stroma of oral squamous cell carcinomas correlates with survival. One of the two polypeptide GalNAc-transferases, GalNAc-T3 or GalNAc-T6, is required for the biosynthesis of GOF by the initiation of a unique O-glycan in the alternative...... deposition of GOF in oral carcinomas. However, neither GalNAc-T3 nor GalNAc-T6 could be detected in stromal fibroblasts. In contrast both transferases were present in the oral squamous carcinoma cells, suggesting that GOF is produced by the oral cancer cells and not only the stromal cells. RT-PCR analysis...

  4. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  5. The role of glutathione transferases in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Ćorić Vesna

    2016-01-01

    Full Text Available Mounting evidence suggest that members of the subfamily of cytosolic glutathione S-transferases (GSTs possess roles far beyond the classical glutathione-dependent enzymatic conjugation of electrophilic metabolites and xenobiotics. Namely, monomeric forms of certain GSTs are capable of forming protein: protein interactions with protein kinases and regulate cell apoptotic pathways. Due to this dual functionality of cytosolic GSTs, they might be implicated in both the development and the progression of renal cell carcinoma (RCC. Prominent genetic heterogeneity, resulting from the gene deletions, as well as from SNPs in the coding and non-coding regions of GST genes, might affect GST isoenzyme profiles in renal parenchyma and therefore serve as a valuable indicator for predicting the risk of cancer development. Namely, GSTs are involved in the biotransformation of several compounds recognized as risk factors for RCC. The most potent carcinogen of polycyclic aromatic hydrocarbon diol epoxides, present in cigarette smoke, is of benzo(apyrene (BPDE, detoxified by GSTs. So far, the relationship between GST genotype and BPDE-DNA adduct formation, in determining the risk for RCC, has not been evaluated in patients with RCC. Although the association between certain individual and combined GST genotypes and RCC risk has been debated in a the literature, the data on the prognostic value of GST polymorphism in patients with RCC are scarce, probably due to the fact that the molecular mechanism supporting the role of GSTs in RCC progression has not been clarified as yet.

  6. Glutathione transferase-mediated benzimidazole-resistance in Fusarium graminearum.

    Science.gov (United States)

    Sevastos, A; Labrou, N E; Flouri, F; Malandrakis, A

    2017-09-01

    Fusarium graminearum laboratory mutants moderately (MR) and highly (HR) benzimidazole-resistant, carrying or not target-site mutations at the β 2 -tubulin gene were utilized in an attempt to elucidate the biochemical mechanism(s) underlying the unique BZM-resistance paradigm of this fungal plant pathogen. Relative expression analysis in the presence or absence of carbendazim (methyl-2-benzimidazole carbamate) using a quantitative Real Time qPCR (RT-qPCR) revealed differences between resistant and the wild-type parental strain although no differences in expression levels of either β 1 - or β 2 -tubulin homologue genes were able to fully account for two of the highly resistant phenotypes. Glutathione transferase (GST)-mediated detoxification was shown to be -at least partly- responsible for the elevated resistance levels of a HR isolate bearing the β 2 -tubulin Phe200Tyr resistance mutation compared with another MR isolate carrying the same mutation. This benzimidazole-resistance mechanism is reported for the first time in F. graminearum. No indications of detoxification involved in benzimidazole resistance were found for the rest of the isolates as revealed by GST and glutathione peroxidase (GPx) activities and bioassays using monoxygenase and hydrolase detoxification enzyme inhibiting synergists. Interestingly, besides the Phe200Tyr mutation-carrying HR isolate, the remaining highly-carbendazim resistant phenotypes could not be associated with any of the target site modification/overproduction, detoxification or reduced uptake-increased efflux mechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Glutathione Transferase GSTπ In Breast Tumors Evaluated By Three Techniques

    Directory of Open Access Journals (Sweden)

    Rafael Molina

    1993-01-01

    Full Text Available The glutathione transferases are involved in intracellular detoxification reactions. One of these, GSTπ, is elevated in some breast cancer cells, particularly cells selected for resistance to anticancer agents. We evaluated GSTπ expression in 60 human breast tumors by three techniques, immunohistochemistry, Northern hybridization, and Western blot analysis. There was a significant positive correlation between the three methods, with complete concordance seen in 64% of the tumors. There was strong, inverse relationship between GSTπ expression and steroid receptor status with all of the techniques utili zed. [n addition, there was a trend toward higher GSTπ expression in poorly differentiated tumors, but no correlation was found between tumor GSTπ content and DNA ploidy or %S-phase. GSTπ expression was also detected in adjacent benign breast tissue as well as infiltrating lymphocytes; this expression may contribute to GSTπ measurements using either Northern hybridization or Western blot analysis. These re sults suggest that immunohistochemistry is the method of choice for measuring GSTπ in breast tumors.

  8. Glycoproteins and sialyl transferase of human B lymphoblastoid cell lines

    International Nuclear Information System (INIS)

    Lui, S.W.L.; Ng, M.H.

    1980-01-01

    We used two radiolabeling methods to study glycoproteins on the surface of lymphoblastoid cells. One of the methods affects tritiation of residues which are oxidized with galactose oxidase and the other causes tritiation of neuraminic acid residues. This approach was shown to allow a better resolution of cell surface glycoproteins than if either method were used alone. Glycoproteins of B 1 - 19 cells which harbor the Epstein-Barr virus genomes were compared with those of its parental cell line, BJAB, which does not harbor the viral genomes. These studies did not reveal a unique viral protein. A 28,000 mol. wt. glycoprotein was found to be the most prominent neuraminic acidlabeled product of B 1 - 19 cells and also of the two other cell lines, Raji and Ly38, which harbor the EBV genomes. A similar molecular weight species from BJAB cells identified by galactose oxidase labeling might be deficient in neuraminic acid residues as it was poorly labeled by the periodate oxidation method. The neuraminic acid content and level of sialyl transferase of BJAB cells were found to be lower than those of the other cell lines studied. (auth.)

  9. S-Nitrosation destabilizes glutathione transferase P1-1.

    Science.gov (United States)

    Balchin, David; Stoychev, Stoyan H; Dirr, Heini W

    2013-12-23

    Protein S-nitrosation is a post-translational modification that regulates the function of more than 500 human proteins. Despite its apparent physiological significance, S-nitrosation is poorly understood at a molecular level. Here, we investigated the effect of S-nitrosation on the activity, structure, stability, and dynamics of human glutathione transferase P1-1 (GSTP1-1), an important detoxification enzyme ubiquitous in aerobes. S-Nitrosation at Cys47 and Cys101 reduces the activity of the enzyme by 94%. Circular dichroism spectroscopy, acrylamide quenching, and amide hydrogen-deuterium exchange mass spectrometry experiments indicate that the loss of activity is caused by the introduction of local disorder at the active site of GSTP1-1. Furthermore, the modification destabilizes domain 1 of GSTP1-1 against denaturation, smoothing the unfolding energy landscape of the protein and introducing a refolding defect. In contrast, S-nitrosation at Cys101 alone introduces a refolding defect in domain 1 but compensates by stabilizing the domain kinetically. These data elucidate the physical basis for the regulation of GSTP1-1 by S-nitrosation and provide general insight into the consequences of S-nitrosation on protein stability and dynamics.

  10. Oral cancer

    Science.gov (United States)

    Cancer - mouth; Mouth cancer; Head and neck cancer; Squamous cell cancer - mouth; Malignant neoplasm - oral ... National Cancer Institute. PDQ lip and oral cavity cancer ... September 25, 2015. www.cancer.gov/types/head-and-neck/hp/lip- ...

  11. Oral Ketamine

    African Journals Online (AJOL)

    Oral Ketamine: A Four-years Experience in ... Key words: Oral Ketamine, Premedication and Oncology. .... form of a letter published in 19835. .... Acta. Anaesthesiol Scandinavica, 1998; 42: 750-758. 4. Murray P. Substitution of another opioid ...

  12. Acetate:succinate CoA-transferase in the hydrogenosomes of Trichomonas vaginalis: Identification and characterization

    NARCIS (Netherlands)

    K.W.A. Grinsven; S. Rosnowsky (Silke); S.W.H. van Weelden (Susanne); S. Pütz (Simone); M. van der Giezen (Mark); W. Martin (William); J.J. van Hellemond (Jaap); A.G.M. Tielens (Aloysius); K. Henze (Katrin)

    2008-01-01

    textabstractAcetate:succinate CoA-transferases (ASCT) are acetate-producing enzymes in hydrogenosomes, anaerobically functioning mitochondria and in the aerobically functioning mitochondria of trypanosomatids. Although acetate is produced in the hydrogenosomes of a number of anaerobic microbial

  13. Glutathione S-transferase gene polymorphisms in presbycusis.

    Science.gov (United States)

    Ateş, Nurcan Aras; Unal, Murat; Tamer, Lülüfer; Derici, Ebru; Karakaş, Sevim; Ercan, Bahadir; Pata, Yavuz Selim; Akbaş, Yücel; Vayisoğlu, Yusuf; Camdeviren, Handan

    2005-05-01

    Glutathione and glutathione-related antioxidant enzymes are involved in the metabolism and detoxification of cytotoxic and carcinogenic compounds as well as reactive oxygen species. Reactive oxygen species generation occurs in prolonged relative hypoperfusion conditions such as in aging. The etiology of presbycusis is much less certain; however, a complex genetic cause is most likely. The effect of aging shows a wide interindividual range; we aimed to investigate whether profiles of (glutathione S-transferase (GST) M1, T1 and P1 genotypes may be associated with the risk of age-related hearing loss. We examined 68 adults with presbycusis and 69 healthy controls. DNA was extracted from whole blood, and the GSTM1, GSTT1 and GSTP1 polymorphisms were determined using a real-time polymerase chain reaction and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of presbycusis were examined by use of logistic regression analyses to calculate odds ratios and 95% confidence intervals. Gene polymorphisms at GSTM1, GSTT1, and GSTP1 in subjects with presbycusis were not significantly different than in the controls (p > 0.05). Also, the combinations of different GSTM1, GSTT1, and GSTP1 genotypes were not an increased risk of presbycusis (p > 0.05). We could not demonstrate any significant association between the GSTM1, GSTT1, and GSTP1 polymorphism and age-related hearing loss in this population. This may be because of our sample size, and further studies need to investigate the exact role of GST gene polymorphisms in the etiopathogenesis of the presbycusis.

  14. Human glutathione transferases catalyzing the bioactivation of anticancer thiopurine prodrugs.

    Science.gov (United States)

    Eklund, Birgitta I; Gunnarsdottir, Sjofn; Elfarra, Adnan A; Mannervik, Bengt

    2007-06-01

    cis-6-(2-Acetylvinylthio)purine (cAVTP) and trans-6-(2-acetylvinylthio)guanine (tAVTG) are thiopurine prodrugs provisionally inactivated by an alpha,beta-unsaturated substituent on the sulfur of the parental thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG). The active thiopurines are liberated intracellularly by glutathione (GSH) in reactions catalyzed by glutathione transferases (GSTs) (EC 2.5.1.18). Catalytic activities of 13 human GSTs representing seven distinct classes of soluble GSTs have been determined. The bioactivation of cAVTP and tAVTG occurs via a transient addition of GSH to the activated double bond of the S-substituent of the prodrug, followed by elimination of the thiopurine. The first of these consecutive reactions is rate-limiting for thiopurine release, but GST-activation of this first addition is shifting the rate limitation to the subsequent elimination. Highly active GSTs reveal the transient intermediate, which is detectable by UV spectroscopy and HPLC analysis. LC/MS analysis of the reaction products demonstrates that the primary GSH conjugate, 4-glutathionylbuten-2-one, can react with a second GSH molecule to form the 4-(bis-glutathionyl)butan-2-one. GST M1-1 and GST A4-4 were the most efficient enzymes with tAVTG, and GST M1-1 and GST M2-2 had highest activity with cAVTP. The highly efficient GST M1-1 is polymorphic and is absent in approximately half of the human population. GST P1-1, which is overexpressed in many cancer cells, had no detectable activity with cAVTP and only minor activity with tAVTG. Other GST-activated prodrugs have targeted GST P1-1-expressing cancer cells. Tumors expressing high levels of GST M1-1 or GST A4-4 can be predicted to be particularly vulnerable to chemotherapy with cAVTP or tAVTG.

  15. Oral Hygiene

    DEFF Research Database (Denmark)

    Sørensen, Marie Toftdahl; Villadsen, Dorte Buxbom

    The aim of the study was to explore how adults with schizo- phrenia describe their lived experiences with oral hygiene. 23 adults with schizophrenia were interviewed within a period of four months in late 2015. Transcriptions of the interviews were analysed using the Reflective Lifeworld Research...... health care professionals and adults with schizophrenia in order to improve oral health, well-being and recovery....

  16. Oral Hygiene

    DEFF Research Database (Denmark)

    Villadsen, Dorte Buxbom; Sørensen, Marie Toftdahl

    2017-01-01

    The aim of the study is to explore how adults with schizophrenia describe their lived experiences with oral hygiene. 23 adults with schizophrenia were interviewed within a period of four months in late 2015. Transcriptions of the interviews were analysed using the Reflective Lifeworld Research ph...... health care professionals and adults with schizophrenia in order to improve oral health, well-being and recovery....

  17. Presence of a Ca2+-sensitive CDPdiglyceride-inositol transferase in canine cardiac sarcoplasmic reticulum

    International Nuclear Information System (INIS)

    Kasinathan, C.; Kirchberger, M.A.

    1988-01-01

    Sarcoplasmic reticulum (SR) and plasma membranes from canine left ventricle were used to evaluate the presence of the enzyme CDPdiglyceride-inositol transferase in these membranes. (K + ,-Ca 2+ )-ATPase activity, a marker for SR, was 79.2 +/- 5.0 (SE) and 11.2 +/- 2.0 μmol x mg -1 x h -1 in SR and plasma membrane preparations, respectively, and (Na + , K + )-ATPase activity, a marker for plasma membranes, was 5.6 +/- 1.2 and 99.2 +/- 8.0 μmol x mg -1 x h -1 , respectively. Contamination of SR and plasma membrane preparations by mitochondria was estimated to be 2% and 8%, respectively, and by Golgi membranes, 0.9% and 1.8%, respectively. The transferase activity detected in the plasma membrane preparation could be accounted for largely, but not entirely, by contaminating SR membranes. The pH optimum for the SR transferase activity was between 8.0 and 9.0. Ca 2+ inhibited the enzyme, half-maximal inhibition occurring at about 10 μM Ca 2+ . No loss of [ 3 H]PtdIns could be detected when membranes were incubated in the presence or absence of Ca 2+ . The Ca 2+ inhibition of the transferase was noncompetitive with respect to CDP-dipalmitin while that with respect to myo-inositol was slightly noncompetitive at low [Ca 2+ ] and became uncompetitive at higher [Ca 2+ ]. It is concluded that CDPdiglyceride-inositol transferase is present on SR membranes and is sensitive to micromolar Ca 2+ . The data are consistent with a putative role for the inhibition of the SR transferase by Ca 2+ and acidic pH in the protection of the SR against calcium overload in ischemic myocardium

  18. Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

    OpenAIRE

    Matsumoto, M; Imagawa, M; Aoki, Y

    2000-01-01

    Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did no...

  19. Oral leukoplakia

    DEFF Research Database (Denmark)

    Holmstrup, Palle; Dabelsteen, Erik

    2016-01-01

    The idea of identifying oral lesions with a precancerous nature, i.e. in the sense of pertaining to a pathologic process with an increased risk for future malignant development, of course is to prevent frank malignancy to occur in the affected area. The most common oral lesion with a precancerous...... nature is oral leukoplakia, and for decades it has been discussed how to treat these lesions. Various treatment modalities, such as systemic therapies and surgical removal, have been suggested. The systemic therapies tested so far include retinoids, extracts of green tea, inhibitors of cyclooxygenase-2...

  20. Oral cancer.

    Science.gov (United States)

    Gerson, S J

    1990-01-01

    In the U.S. oral cancer accounts for 2.1% of all cancers and 1% of cancer deaths. Two to three times as many males as females are affected. Blacks have more intra-oral cancer than whites, and their incidence and mortality rates have increased in recent years. The etiologic process very likely involves several factors. The major etiologic agents are tobacco (all types) and alcoholic beverages. Herpes simplex virus, human papilloma virus, and Candida have been implicated. Host factors include poor state of dentition, nutritional aberrations, cirrhosis of liver, lichen planus, and immunologic impairmant. Cellular changes include amplification of some oncogenes, alterations in antigen expression, production of gamma-glutamyl transpeptidase, and disturbance of keratin and involucrin production. Experimentally, cancer is readily produced on the hamster cheek pouch and rat oral mucosa. Unlike oral cancer in humans, most experimental lesions are exophytic, and they rarely metastasize.

  1. Oral sex.

    Science.gov (United States)

    1996-04-05

    The Gay and Lesbian Medical Association urges HIV prevention specialists to regard male-to-male oral-genital sex as a low-risk activity and concentrate instead on the danger of unprotected anal intercourse. According to the association, the confusion and mixed messages surrounding oral sex are harming efforts to encourage gay men to make rational choices about truly risky behavior. The recommendations appear in the association's position paper issued March 19, 1996.

  2. Oral Cancer Screening

    Science.gov (United States)

    ... decrease the risk of oral cavity and oropharyngeal cancer. Oral cavity, pharyngeal, and laryngeal cancer are diseases in ... and treatment of oral cavity, pharyngeal, and laryngeal cancer: Oral Cavity and Oropharyngeal Cancer Prevention Lip and Oral ...

  3. Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma

    International Nuclear Information System (INIS)

    Hayes, J.D.; Gilligan, D.; Beckett, G.J.

    1983-01-01

    A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements. (Auth.)

  4. Purification of human hepatic glutathione S-transferases and the development of a radioimmunoassay for their measurement in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, J.D.; Gilligan, D.; Beckett, G.J. (Edinburgh Univ. (UK). Dept. of Clinical Chemistry); Chapman, B.J. (Royal Infirmary, Edinburgh (UK))

    1983-10-31

    A purification scheme is described for six human hepatic glutathione S-transferases from a single liver. Five of the transferases comprised Ya monomers and had a molecular mass of 44000. The remaining enzyme comprised Yb monomers and had a molecular mass of 47000. Data are presented demonstrating that there are at least two distinct Ya monomers. A radioimmunoassay has been developed that has sufficient precision and sensitivity to allow direct measurement of glutathione S-transferase concentrations in unextracted plasma. A comparison of aminotransferase and glutathione S-transferase levels, in three patients who had taken a paracetamol overdose, indicated that glutathione S-transferase measurements provided a far more sensitive index of hepatocellular integrity than the more conventional aminotransferase measurements.

  5. Glutathione s-transferase isoenzymes in relation to their role in detoxification of xenobiotics

    NARCIS (Netherlands)

    Vos, R.M.E.

    1989-01-01

    The glutathione S-transferases (GST) are a family of isoenzymes serving a major part in the biotransformation of many reactive compounds. The isoenzymes from rat, man and mouse are divided into three classes, alpha, mu and pi, on the basis of similar structural and enzymatic

  6. Isolation and characterization of an auxin-inducible glutathione S-transferase gene of Arabidopsis thaliana

    NARCIS (Netherlands)

    Kop, D.A.M. van der; Schuyer, M.; Scheres, B.J.G.; Zaal, B.J. van der; Hooykaas, P.J.J.

    1996-01-01

    Genes homologous to the auxin-inducible Nt103 glutathione S-transferase (GST) gene of tobacco, were isolated from a genomic library of Arabidopsis thaliana. We isolated a λ clone containing an auxin-inducible gene, At103-1a, and part of a constitutively expressed gene, At103-1b. The coding regions

  7. Global deletion of glutathione S-Transferase A4 exacerbates developmental nonalcoholic steatohepatitis

    Science.gov (United States)

    We established a mouse model of developmental nonalcoholic steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 (Gsta4-/-)/peroxisome proliferator activated receptor a (Ppara-/-) double knockout 129/SvJ mice for 12 weeks from weaning. We us...

  8. Involvement of human glutathione S-transferase isoenzymes in the conjugation of cyclophosphamide metabolites with glutathione

    NARCIS (Netherlands)

    Dirven, H.A.A.M.; Ommen, B. van; Bladeren, P.J. van

    1994-01-01

    Alkylating agents can be detoxified by conjugation with glutathione (GSH). One of the physiological significances of this lies in the observation that cancer cells resistant to the cytotoxic effects of alkylating agents have higher levels of GSH and high glutathione S-transferase (GST) activity.

  9. The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization

    DEFF Research Database (Denmark)

    Ross-Hansen, K; Linneberg, A; Johansen, J D

    2013-01-01

    BACKGROUND: Contact sensitization is frequent in the general population and arises from excessive or repeated skin exposure to chemicals and metals. However, little is known about its genetic susceptibility. OBJECTIVES: To determine the role of polymorphisms of glutathione S-transferase (GST) genes...

  10. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver.

    NARCIS (Netherlands)

    Oetari, S.; Sudibyo, M.; Commandeur, J.N.M.; Samhoedi, R.; Vermeulen, N.P.E.

    1996-01-01

    The stability of curcumin, as well as the interactions between curcumin and cytochrome P450s (P450s) and glutathione S-transferases (GSTs) in rat liver, were studied. Curcumin is relatively unstable in phosphate buffer at pH 7.4. The stability of curcumin was strongly improved by lowering the pH or

  11. Bisubstrate Kinetics of Glutathione S-Transferase: A Colorimetric Experiment for the Introductory Biochemistry Laboratory

    Science.gov (United States)

    Stefanidis, Lazaros; Scinto, Krystal V.; Strada, Monica I.; Alper, Benjamin J.

    2018-01-01

    Most biochemical transformations involve more than one substrate. Bisubstrate enzymes catalyze multiple chemical reactions in living systems and include members of the transferase, oxidoreductase, and ligase enzyme classes. Working knowledge of bisubstrate enzyme kinetic models is thus of clear importance to the practicing biochemist. However,…

  12. Association study on glutathione S-transferase omega 1 and 2 and familial ALS

    NARCIS (Netherlands)

    van de Giessen, Elsmarieke; Fogh, Isabella; Gopinath, Sumana; Smith, Bradley; Hu, Xun; Powell, John; Andersen, Peter; Nicholson, Garth; Al Chalabi, Ammar; Shaw, Christopher E.

    2008-01-01

    Glutathione S-transferase omega 1 and 2 (GSTO1 and 2) protect from oxidative stress, a possible pathogenic mechanism underlying the pathogenesis of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Significant association of age of onset in Alzheimer's

  13. Primary overproduction of urate caused by a partial deficiency of hypoxanthine-guanine phosphoribosyl transferase

    International Nuclear Information System (INIS)

    Cassidy, M.; Gregory, M.C.; Harley, E.H.

    1980-01-01

    Inherited enzyme deficiencies are found in a small proportion of patients with gout who produce an excess of uric acid. The clinical, biochemical and therapeutic aspects of a case of hyperuricaemia caused by an atypical mutant hypoxanthine-guanine phophoribosyl transferase are presented. Urate overproduction was moderate and controlled by allopurinol therapy

  14. Glutathione S-transferase genotype and p53 mutations in adenocarcinoma of the small intestine

    DEFF Research Database (Denmark)

    Pedersen, Lisbeth Nørum; Kaerlev, L; Stubbe Teglbjaerg, P

    2003-01-01

    Adenocarcinoma of the small intestine (ASI) is a rare disease of unknown aetiology. The glutathione S-transferase M1 (GSTM1) enzyme catalyses the detoxification of compounds involved in carcinogenesis of adenocarcinoma of the stomach, colon and lung, including constituents of tobacco smoke. We in...

  15. Antibiotic inhibition of the movement of tRNA substrates through a peptidyl transferase cavity

    DEFF Research Database (Denmark)

    Porse, B T; Rodriguez-Fonseca, C; Leviev, I

    1996-01-01

    The present review attempts to deal with movement of tRNA substrates through the peptidyl transferase centre on the large ribosomal subunit and to explain how this movement is interrupted by antibiotics. It builds on the concept of hybrid tRNA states forming on ribosomes and on the observed movem...

  16. Inhibition of rat, mouse, and human glutathione S-transferase by eugenol and its oxidation products

    NARCIS (Netherlands)

    Rompelberg, C.J.M.; Ploemen, J.H.T.M.; Jespersen, S.; Greef, J. van der; Verhagen, H.; Bladeren, P.J. van

    1996-01-01

    The irreversible and reversible inhibition of glutathione S-transferases (GSTs) by eugenol was studied in rat, mouse and man. Using liver cytosol of human, rat and mouse, species differences were found in the rate of irreversible inhibition of GSTs by eugenol in the presence of the enzyme

  17. Functional characterization of glutathione S-transferases associated with insecticide resistance in Tetranychus urticae

    NARCIS (Netherlands)

    Pavlidi, N.; Tseliou, V.; Riga, M.; Nauen, R.; Van Leeuwen, T.; Labrou, N.E.; Vontas, J.

    2015-01-01

    The two-spotted spider mite Tetranychus urticae is one of the most important agricultural pests world-wide. It is extremely polyphagous and develops resistance to acaricides. The overexpression of several glutathione S-transferases (GSTs) has been associated with insecticide resistance. Here, we

  18. Oral candidiasis.

    Science.gov (United States)

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2010-01-01

    Full Text Available Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency.

  20. Photoaffinity labelling of the active site of the rat glutathione transferases 3-3 and 1-1 and human glutathione transferase A1-1.

    OpenAIRE

    Cooke, R J; Björnestedt, R; Douglas, K T; McKie, J H; King, M D; Coles, B; Ketterer, B; Mannervik, B

    1994-01-01

    The glutathione transferases (GSTs) form a group of enzymes responsible for a wide range of molecular detoxications. The photoaffinity label S-(2-nitro-4-azidophenyl)glutathione was used to study the hydrophobic region of the active site of the rat liver GST 1-1 and 2-2 isoenzymes (class Alpha) as well as the rat class-Mu GST 3-3. Photoaffinity labelling was carried out using a version of S-(2-nitro-4-azidophenyl)glutathione tritiated in the arylazido ring. The labelling occurred with higher ...

  1. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

  2. ABO blood group antigens in oral mucosa. What is new?

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    2002-01-01

    which represent secondary gene products. They are synthesized in a stepwise fashion from a precursor by the action of different glycosyltransferases. In non-keratinized oral mucosa, a sequential elongation of the carbohydrates is associated with differentiation of epithelial cells, resulting...... in expression of precursors on basal cells and A/B antigens on spinous cells. Reduction or complete deletion of A/B antigen expression in oral carcinomas has been reported, a phenotypic change that is correlated with invasive and metastatic potential of the tumours and with the mortality rates of the patients....... Disappearance of the antigens is ascribed to the absence of A or B transferase gene expression. Several studies have shown that loss of A and B antigen expression is associated with increased cell motility, invasion in matrigel, and tumourigenecity in syngenic animals. In vivo studies of human oral wound...

  3. Oral care.

    Science.gov (United States)

    Hitz Lindenmüller, Irène; Lambrecht, J Thomas

    2011-01-01

    Adequate dental and oral hygiene may become a challenge for all users and especially for elderly people and young children because of their limited motor skills. The same holds true for patients undergoing/recovering from chemo-/radiotherapy with accompanying sensitive mucosal conditions. Poor dental hygiene can result in tooth decay, gingivitis, periodontitis, tooth loss, bad breath (halitosis), fungal infection and gum diseases. The use of a toothbrush is the most important measure for oral hygiene. Toothbrushes with soft bristles operated carefully by hand or via an electric device help to remove plaque and to avoid mucosal trauma. A handlebar with a grip cover can be helpful for manually disabled patients or for those with reduced motor skills. In case of oral hygiene at the bedside or of patients during/after chemo-/radiotherapy a gauze pad can be helpful for gently cleaning the teeth, gums and tongue. The use of fluoride toothpaste is imperative for the daily oral hygiene. Detergents such as sodium lauryl sulphate improve the cleaning action but may also dehydrate and irritate the mucous membrane. The use of products containing detergents and flavouring agents (peppermint, menthol, cinnamon) should therefore be avoided by bedridden patients or those with dry mouth and sensitive mucosa. Aids for suitable interdental cleaning, such as dental floss, interdental brushes or dental sticks, are often complicated to operate. Their correct use should be instructed by healthcare professionals. To support dental care, additional fluoridation with a fluoride gel or rinse can be useful. Products further containing antiseptics such as chlorhexidine or triclosan reduce the quantity of bacteria in the mouth. For patients undergoing or having undergone radio-/chemotherapy, a mouthwash that concomitantly moisturizes the oral mucosa is advisable. Copyright © 2011 S. Karger AG, Basel.

  4. Oral Health and Aging

    Science.gov (United States)

    ... please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Past Issues / Summer 2016 Table of Contents Jerrold ... they may need. Read More "Oral Health and Aging" Articles Oral Health and Aging / 4 Myths About ...

  5. A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast

    DEFF Research Database (Denmark)

    Kampranis, S C; Damianova, R; Atallah, M

    2000-01-01

    The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allows...... for the identification of plant genes, which inhibit either directly or indirectly the lethal phenotype of Bax. Using this method a number of cDNA clones were isolated, the more potent of which encodes a protein homologous to the class theta glutathione S-transferases. This Bax-inhibiting (BI) protein was expressed...... in Escherichia coli and found to possess glutathione S-transferase (GST) and weak glutathione peroxidase (GPX) activity. Expression of Bax in yeast decreases the intracellular levels of total glutathione, causes a substantial reduction of total cellular phospholipids, diminishes the mitochondrial membrane...

  6. Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity

    DEFF Research Database (Denmark)

    Pedersen, Johannes W; Bennett, Eric P; Schjoldager, Katrine T-B G

    2011-01-01

    UDP-GalNAc:polypeptide a-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection...... of glycosylation sites by GalNAc-Ts: confined sequence recognition by the catalytic domain alone, and concerted recognition of acceptor sites and adjacent GalNAc-glycosylated sites by the catalytic and lectin domains, respectively. Thus far, only the catalytic domain has been shown to have peptide sequence...... on sequences of mucins MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC7 as well as a random glycopeptide bead library, we examined the binding properties of four different lectin domains. The lectin domains of GalNAc-T1, -T2, -T3, and -T4 bound different subsets of small glycopeptides. These results indicate...

  7. Development of isoform-specific sensors of polypeptide GalNAc-transferase activity

    DEFF Research Database (Denmark)

    Song, Lina; Bachert, Collin; Schjoldager, Katrine T

    2014-01-01

    sequence influenced their activity and required modification, which we carried out based on previous in vitro work. Significantly, the modified T2 and T3 sensors were activated only in cells lacking their corresponding isozymes. Thus, we have developed T2- and T3-specific sensors that will be valuable......Humans express up to 20 isoforms of GalNAc-transferase (herein T1-T20) that localize to the Golgi apparatus and initiate O-glycosylation. Regulation of this enzyme family affects a vast array of proteins transiting the secretory pathway and diseases arise upon misregulation of specific isoforms....... Surprisingly, molecular probes to monitor GalNAc-transferase activity are lacking and there exist no effective global or isoform-specific inhibitors. Here we describe the development of T2- and T3-isoform specific fluorescence sensors that traffic in the secretory pathway. Each sensor yielded little signal...

  8. Caractérisation biochimique et fonctionnelle de glutathion-S-transferases (GSTs) chez Phanerochaete chrysosporium

    OpenAIRE

    Anak Ngadin , Andrew

    2011-01-01

    Phanerochaete chrysosporium is a ligninolytic fungus widely studied because of its capacities to degrade wood and xenobiotics through an extracellular enzymatic system. Its genome has been sequenced and has provided researchers with a complete inventory of the predicted proteins produced by this organism. This has allowed the description of many protein superfamilies. Among them, Glutathione S-transferases (GSTs) constitute a complex and widespread superfamily classified as enzymes of seconda...

  9. Imidazopyridine and Pyrazolopiperidine Derivatives as Novel Inhibitors of Serine Palmitoyl Transferase.

    Science.gov (United States)

    Genin, Michael J; Gonzalez Valcarcel, Isabel C; Holloway, William G; Lamar, Jason; Mosior, Marian; Hawkins, Eric; Estridge, Thomas; Weidner, Jeffrey; Seng, Thomas; Yurek, David; Adams, Lisa A; Weller, Jennifer; Reynolds, Vincent L; Brozinick, Joseph T

    2016-06-23

    To develop novel treatments for type 2 diabetes and dyslipidemia, we pursued inhibitors of serine palmitoyl transferase (SPT). To this end compounds 1 and 2 were developed as potent SPT inhibitors in vitro. 1 and 2 reduce plasma ceramides in rodents, have a slight trend toward enhanced insulin sensitization in DIO mice, and reduce triglycerides and raise HDL in cholesterol/cholic acid fed rats. Unfortunately these molecules cause a gastric enteropathy after chronic dosing in rats.

  10. The phosphopantetheinyl transferases: catalysis of a post-translational modification crucial for life

    DEFF Research Database (Denmark)

    Beld, Joris; Sonnenschein, Eva; Vickery, Christopher R.

    2013-01-01

    Covering: up to 2013 Although holo-acyl carrier protein synthase, AcpS, a phosphopantetheinyl transferase (PPTase), was characterized in the 1960s, it was not until the publication of the landmark paper by Lambalot et al. in 1996 that PPTases garnered wide-spread attention being classified...... knowledge on this class of enzymes that post-translationally install a 4′-phosphopantetheine arm on various carrier proteins....

  11. A 4'-phosphopantetheinyl transferase mediates non-ribosomal peptide synthetase activation in Aspergillus fumigatus.

    Science.gov (United States)

    Neville, Claire; Murphy, Alan; Kavanagh, Kevin; Doyle, Sean

    2005-04-01

    Aspergillus fumigatus is a significant human pathogen. Non-ribosomal peptide (NRP) synthesis is thought to be responsible for a significant proportion of toxin and siderophore production in the organism. Furthermore, it has been shown that 4'-phosphopantetheinylation is required for the activation of key enzymes involved in non-ribosomal peptide synthesis in other species. Here we report the cloning, recombinant expression and functional characterisation of a 4'-phosphopantetheinyl transferase from A. fumigatus and the identification of an atypical NRP synthetase (Afpes1), spanning 14.3 kb. Phylogenetic analysis has shown that the NRP synthetase exhibits greatest identity to NRP synthetases from Metarhizium anisolpiae (PesA) and Alternaria brassicae (AbrePsy1). Northern hybridisation and RT-PCR analysis have confirmed that both genes are expressed in A. fumigatus. A 120 kDa fragment of the A. fumigatus NRP synthetase, containing a putative thiolation domain, was cloned and expressed in the baculovirus expression system. Detection of a 4'-phosphopantetheinylated peptide (SFSAMK) from this protein, by MALDI-TOF mass spectrometric analysis after coincubation of the 4'-phosphopantetheinyl transferase with the recombinant NRP synthetase fragment and acetyl CoA, confirms that it is competent to play a role in NRP synthetase activation in A. fumigatus. The 4'-phosphopantetheinyl transferase also activates, by 4'-phosphopantetheinylation, recombinant alpha-aminoadipate reductase (Lys2p) from Candida albicans, a key enzyme involved in lysine biosynthesis.

  12. Interactions of photoactive DNAs with terminal deoxynucleotidyl transferase: Identification of peptides in the DNA binding domain

    International Nuclear Information System (INIS)

    Farrar, Y.J.K.; Evans, R.K.; Beach, C.M.; Coleman, M.S.

    1991-01-01

    Terminal deoxynucleotidyl transferase (terminal transferase) was specifically modified in the DNA binding site by a photoactive DNA substrate (hetero-40-mer duplex containing eight 5-azido-dUMP residues at one 3' end). Under optimal photolabeling conditions, 27-40% of the DNA was covalently cross-linked to terminal transferase. The specificity of the DNA and protein interaction was demonstrated by protection of photolabeling at the DNA binding domain with natural DNA substrates. In order to recover high yields of modified peptides from limited amounts of starting material, protein modified with 32 P-labeled photoactive DNA and digested with trypsin was extracted 4 times with phenol followed by gel filtration chromatography. All peptides not cross-linked to DNA were extracted into the phenol phase while the photolyzed DNA and the covalently cross-linked peptides remained in the aqueous phase. The 32 P-containing peptide-DNA fraction was subjected to amino acid sequence analysis. Two sequences, Asp 221 -Lys 231 (peptide B8) and Cys 234 -Lys 249 (peptide B10), present in similar yield, were identified. Structure predictions placed the two peptides in an α-helical array of 39 angstrom which would accommodate a DNA helix span of 11 nucleotides. These peptides share sequence similarity with a region in DNA polymerase β that has been implicated in the binding of DNA template

  13. Glutathione S - transferases class Pi and Mi and their significance in oncology

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2017-06-01

    Full Text Available In this article the current data, which shows that glutathione S-transferases (GST class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

  14. Glutathione S - transferases class Pi and Mi and their significance in oncology.

    Science.gov (United States)

    Marchewka, Zofia; Piwowar, Agnieszka; Ruzik, Sylwia; Długosz, Anna

    2017-06-19

    In this article the current data, which shows that glutathione S-transferases (GST) class Pi and Mi are interesting and promising biomarkers in acute and chronic inflammatory processes as well as in the oncology, were presented based on the review of the latest experimental and clinical studies. The article shows their characteristics, functions and participation (direct - GST Pi, indirect - GST Mi) in the regulation of signaling pathways of JNK kinases, which are involved in cell differentiation. Overexpression of glutathione S-transferases class Pi and Mi in many cancer cells plays a key role in cancer treatment, making them resistant to chemotherapy. GST isoenzymes are involved in the metabolism of various types of xenobiotics and endogenous substrates, so their altered expression in cancer tissues as well as in serum and urine could be an important potential marker of the cancer and an indicator of oxidative stress. The study shows the role of glutathione S-transferases in redox homeostasis of tumor cells and in the mechanism of resistance to anticancer drugs.

  15. Characterization of Affinity-Purified Isoforms of Acinetobacter calcoaceticus Y1 Glutathione Transferases

    Directory of Open Access Journals (Sweden)

    Chin-Soon Chee

    2014-01-01

    Full Text Available Glutathione transferases (GST were purified from locally isolated bacteria, Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion exchange, and their substrate specificities were investigated. SDS-polyacrylamide gel electrophoresis revealed that the purified GST resolved into a single band with a molecular weight (MW of 23 kDa. 2-dimensional (2-D gel electrophoresis showed the presence of two isoforms, GST1 (pI 4.5 and GST2 (pI 6.2 with identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active towards all substrates except hydrogen peroxide. This demonstrated that GST1 possessed peroxidase activity which was absent in GST2. This study also showed that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase and F0KKB0 (glutathione S-transferase III of Acinetobacter calcoaceticus strain PHEA-2, respectively.

  16. Characterization of Affinity-Purified Isoforms of Acinetobacter calcoaceticus Y1 Glutathione Transferases

    Science.gov (United States)

    Chee, Chin-Soon; Tan, Irene Kit-Ping; Alias, Zazali

    2014-01-01

    Glutathione transferases (GST) were purified from locally isolated bacteria, Acinetobacter calcoaceticus Y1, by glutathione-affinity chromatography and anion exchange, and their substrate specificities were investigated. SDS-polyacrylamide gel electrophoresis revealed that the purified GST resolved into a single band with a molecular weight (MW) of 23 kDa. 2-dimensional (2-D) gel electrophoresis showed the presence of two isoforms, GST1 (pI 4.5) and GST2 (pI 6.2) with identical MW. GST1 was reactive towards ethacrynic acid, hydrogen peroxide, 1-chloro-2,4-dinitrobenzene, and trans,trans-hepta-2,4-dienal while GST2 was active towards all substrates except hydrogen peroxide. This demonstrated that GST1 possessed peroxidase activity which was absent in GST2. This study also showed that only GST2 was able to conjugate GSH to isoproturon, a herbicide. GST1 and GST2 were suggested to be similar to F0KLY9 (putative glutathione S-transferase) and F0KKB0 (glutathione S-transferase III) of Acinetobacter calcoaceticus strain PHEA-2, respectively. PMID:24892084

  17. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Extractions and Other Oral Surgeries Extractions and Other Oral Surgeries Oral and maxillofacial surgeons surgically treat the soft ... Extractions and Other Oral Surgeries Extractions and Other Oral Surgeries Oral and maxillofacial surgeons surgically treat the soft ...

  18. Towards understanding oral health

    NARCIS (Netherlands)

    Zaura, E.; ten Cate, J.M.

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term ‘oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain

  19. Catalysis of Silver catfish Major Hepatic Glutathione Transferase proceeds via rapid equilibrium sequential random Mechanism

    Directory of Open Access Journals (Sweden)

    Ayodele O. Kolawole

    Full Text Available Fish hepatic glutathione transferases are connected with the elimination of intracellular pollutants and detoxification of organic micro-pollutants in their aquatic ecosystem. The two-substrate steady state kinetic mechanism of Silver catfish (Synodontis eupterus major hepatic glutathione transferases purified to apparent homogeneity was explored. The enzyme was dimeric enzyme with a monomeric size of 25.6 kDa. Initial-velocity studies and Product inhibition patterns by methyl glutathione and chloride with respect to GSH-CDNB; GSH-ρ-nitrophenylacetate; and GSH-Ethacrynic acid all conforms to a rapid equilibrium sequential random Bi Bi kinetic mechanism rather than steady state sequential random Bi Bi kinetic. α was 2.96 ± 0.35 for the model. The pH profile of Vmax/KM (with saturating 1-chloro-2,4-dinitrobenzene and variable GSH concentrations showed apparent pKa value of 6.88 and 9.86. Inhibition studies as a function of inhibitor concentration show that the enzyme is a homodimer and near neutral GST. The enzyme poorly conjugates 4-hydroxylnonenal and cumene hydroperoxide and may not be involved in oxidative stress protection. The seGST is unique and overwhelmingly shows characteristics similar to those of homodimeric class Pi GSTs, as was indicated by its kinetic mechanism, substrate specificity and inhibition studies. The rate- limiting step, probably the product release, of the reaction is viscosity-dependent and is consequential if macro-viscosogen or micro-viscosogen. Keywords: Silver catfish, Glutathione transferase, Steady-state, Kinetic mechanism, Inhibition

  20. Characterization of glutathione transferases involved in the pathogenicity of Alternaria brassicicola.

    Science.gov (United States)

    Calmes, Benoit; Morel-Rouhier, Mélanie; Bataillé-Simoneau, Nelly; Gelhaye, Eric; Guillemette, Thomas; Simoneau, Philippe

    2015-06-18

    Glutathione transferases (GSTs) represent an extended family of multifunctional proteins involved in detoxification processes and tolerance to oxidative stress. We thus anticipated that some GSTs could play an essential role in the protection of fungal necrotrophs against plant-derived toxic metabolites and reactive oxygen species that accumulate at the host-pathogen interface during infection. Mining the genome of the necrotrophic Brassica pathogen Alternaria brassicicola for glutathione transferase revealed 23 sequences, 17 of which could be clustered into the main classes previously defined for fungal GSTs and six were 'orphans'. Five isothiocyanate-inducible GSTs from five different classes were more thoroughly investigated. Analysis of their catalytic properties revealed that two GSTs, belonging to the GSTFuA and GTT1 classes, exhibited GSH transferase activity with isothiocyanates (ITC) and peroxidase activity with cumene hydroperoxide, respectively. Mutant deficient for these two GSTs were however neither more susceptible to ITC nor less aggressive than the wild-type parental strain. By contrast mutants deficient for two other GSTs, belonging to the Ure2pB and GSTO classes, were distinguished by their hyper-susceptibility to ITC and low aggressiveness against Brassica oleracea. In particular AbGSTO1 could participate in cell tolerance to ITC due to its glutathione-dependent thioltransferase activity. The fifth ITC-inducible GST belonged to the MAPEG class and although it was not possible to produce the soluble active form of this protein in a bacterial expression system, the corresponding deficient mutant failed to develop normal symptoms on host plant tissues. Among the five ITC-inducible GSTs analyzed in this study, three were found essential for full aggressiveness of A. brassicicola on host plant. This, to our knowledge is the first evidence that GSTs might be essential virulence factors for fungal necrotrophs.

  1. Glutathione Transferase from Trichoderma virens Enhances Cadmium Tolerance without Enhancing Its Accumulation in Transgenic Nicotiana tabacum

    Science.gov (United States)

    Dixit, Prachy; Mukherjee, Prasun K.; Ramachandran, V.; Eapen, Susan

    2011-01-01

    Background Cadmium (Cd) is a major heavy metal pollutant which is highly toxic to plants and animals. Vast agricultural areas worldwide are contaminated with Cd. Plants take up Cd and through the food chain it reaches humans and causes toxicity. It is ideal to develop plants tolerant to Cd, without enhanced accumulation in the edible parts for human consumption. Glutathione transferases (GST) are a family of multifunctional enzymes known to have important roles in combating oxidative stresses induced by various heavy metals including Cd. Some GSTs are also known to function as glutathione peroxidases. Overexpression/heterologous expression of GSTs is expected to result in plants tolerant to heavy metals such as Cd. Results Here, we report cloning of a glutathione transferase gene from Trichoderma virens, a biocontrol fungus and introducing it into Nicotiana tabacum plants by Agrobacterium-mediated gene transfer. Transgenic nature of the plants was confirmed by Southern blot hybridization and expression by reverse transcription PCR. Transgene (TvGST) showed single gene Mendelian inheritance. When transgenic plants expressing TvGST gene were exposed to different concentrations of Cd, they were found to be more tolerant compared to wild type plants, with transgenic plants showing lower levels of lipid peroxidation. Levels of different antioxidant enzymes such as glutathione transferase, superoxide dismutase, ascorbate peroxidase, guiacol peroxidase and catalase showed enhanced levels in transgenic plants expressing TvGST compared to control plants, when exposed to Cd. Cadmium accumulation in the plant biomass in transgenic plants were similar or lower than wild-type plants. Conclusion The results of the present study suggest that transgenic tobacco plants expressing a Trichoderma virens GST are more tolerant to Cd, without enhancing its accumulation in the plant biomass. It should be possible to extend the present results to crop plants for developing Cd tolerance and

  2. Glutathione transferase from Trichoderma virens enhances cadmium tolerance without enhancing its accumulation in transgenic Nicotiana tabacum.

    Directory of Open Access Journals (Sweden)

    Prachy Dixit

    Full Text Available BACKGROUND: Cadmium (Cd is a major heavy metal pollutant which is highly toxic to plants and animals. Vast agricultural areas worldwide are contaminated with Cd. Plants take up Cd and through the food chain it reaches humans and causes toxicity. It is ideal to develop plants tolerant to Cd, without enhanced accumulation in the edible parts for human consumption. Glutathione transferases (GST are a family of multifunctional enzymes known to have important roles in combating oxidative stresses induced by various heavy metals including Cd. Some GSTs are also known to function as glutathione peroxidases. Overexpression/heterologous expression of GSTs is expected to result in plants tolerant to heavy metals such as Cd. RESULTS: Here, we report cloning of a glutathione transferase gene from Trichoderma virens, a biocontrol fungus and introducing it into Nicotiana tabacum plants by Agrobacterium-mediated gene transfer. Transgenic nature of the plants was confirmed by Southern blot hybridization and expression by reverse transcription PCR. Transgene (TvGST showed single gene Mendelian inheritance. When transgenic plants expressing TvGST gene were exposed to different concentrations of Cd, they were found to be more tolerant compared to wild type plants, with transgenic plants showing lower levels of lipid peroxidation. Levels of different antioxidant enzymes such as glutathione transferase, superoxide dismutase, ascorbate peroxidase, guiacol peroxidase and catalase showed enhanced levels in transgenic plants expressing TvGST compared to control plants, when exposed to Cd. Cadmium accumulation in the plant biomass in transgenic plants were similar or lower than wild-type plants. CONCLUSION: The results of the present study suggest that transgenic tobacco plants expressing a Trichoderma virens GST are more tolerant to Cd, without enhancing its accumulation in the plant biomass. It should be possible to extend the present results to crop plants for

  3. Oral dirofilariasis

    Directory of Open Access Journals (Sweden)

    Mahija Janardhanan

    2014-01-01

    Full Text Available Filariasis affecting animals can rarely cause infections in human beings through the accidental bite of potential vectors. The resulting infection in man, known as zoonotic filariasis occur worldwide. Human dirofilariasis, the most common zoonotic filariasis, is caused by the filarial worm belonging to the genus Dirofilaria. Dirofilarial worms, which are recognized as pathogenic in man can cause nodular lesions in the lung, subcutaneous tissue, peritoneal cavity or eyes. Oral dirofilariasis is extremely rare and only a few cases have been documented. We report an interesting case of dirofilariasis due to Dirofilaria repens involving buccal mucosa in a patient who presented with a facial swelling. The clinical features, diagnostic issues and treatment aspects are discussed. This paper stresses the importance of considering dirofilariasis as differential diagnosis for subcutaneous swelling of the face, especially in areas where it is endemic.

  4. Oral dirofilariasis.

    Science.gov (United States)

    Janardhanan, Mahija; Rakesh, S; Savithri, Vindhya

    2014-01-01

    Filariasis affecting animals can rarely cause infections in human beings through the accidental bite of potential vectors. The resulting infection in man, known as zoonotic filariasis occur worldwide. Human dirofilariasis, the most common zoonotic filariasis, is caused by the filarial worm belonging to the genus Dirofilaria. Dirofilarial worms, which are recognized as pathogenic in man can cause nodular lesions in the lung, subcutaneous tissue, peritoneal cavity or eyes. Oral dirofilariasis is extremely rare and only a few cases have been documented. We report an interesting case of dirofilariasis due to Dirofilaria repens involving buccal mucosa in a patient who presented with a facial swelling. The clinical features, diagnostic issues and treatment aspects are discussed. This paper stresses the importance of considering dirofilariasis as differential diagnosis for subcutaneous swelling of the face, especially in areas where it is endemic.

  5. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    OpenAIRE

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-01-01

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lac...

  6. Resistance to the Peptidyl Transferase Inhibitor Tiamulin Caused by Mutation of Ribosomal Protein L3

    OpenAIRE

    Bøsling, Jacob; Poulsen, Susan M.; Vester, Birte; Long, Katherine S.

    2003-01-01

    The antibiotic tiamulin targets the 50S subunit of the bacterial ribosome and interacts at the peptidyl transferase center. Tiamulin-resistant Escherichia coli mutants were isolated in order to elucidate mechanisms of resistance to the drug. No mutations in the rRNA were selected as resistance determinants using a strain expressing only a plasmid-encoded rRNA operon. Selection in a strain with all seven chromosomal rRNA operons yielded a mutant with an A445G mutation in the gene coding for ri...

  7. Generation of Active Bovine Terminal Deoxynucleotidyl Transferase (TdT in E.coli

    Directory of Open Access Journals (Sweden)

    Wee Liang Kuan

    2010-08-01

    Full Text Available A synthetic gene encoding bovine terminal deoxynucleotidyl transferase (TdT was generated, cloned into an expression vector and expressed in E.coli. The effects of altering culture and induction conditions on the nature of recombinant protein production were investigated. This led to the expression of active recombinant bovine TdT in E.coli. After purification and characterisation, the activity of the enzyme was assessed in a biological assay for apoptosis. The process described in this report enables the economical production of TdT for high throughput applications.

  8. Generation of Active Bovine Terminal Deoxynucleotidyl Transferase (TdT in E.coli

    Directory of Open Access Journals (Sweden)

    Wee Liang Kuan

    2010-01-01

    Full Text Available A synthetic gene encoding bovine terminal deoxynucleotidyl transferase (TdT was generated, cloned into an expression vector and expressed in E.coli. The effects of altering culture and induction conditions on the nature of recombinant protein production were investigated. This led to the expression of active recombinant bovine TdT in E.coli. After purification and characterisation, the activity of the enzyme was assessed in a biological assay for apoptosis. The process described in this report enables the economical production of TdT for high throughput applications.

  9. The O-GlcNAc Transferase Intellectual Disability Mutation L254F Distorts the TPR Helix.

    Science.gov (United States)

    Gundogdu, Mehmet; Llabrés, Salomé; Gorelik, Andrii; Ferenbach, Andrew T; Zachariae, Ulrich; van Aalten, Daan M F

    2018-05-17

    O-linked β-N-acetyl- D -glucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential post-translational modification that is abundant in the brain. Recently, OGT mutations have been associated with intellectual disability, although it is not understood how they affect OGT structure and function. Using a multi-disciplinary approach we show that the L254F OGT mutation leads to conformational changes of the tetratricopeptide repeats and reduced activity, revealing the molecular mechanisms contributing to pathogenesis. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Oral sex, oral health and orogenital infections

    Directory of Open Access Journals (Sweden)

    Rajiv Saini

    2010-01-01

    Full Text Available Oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents. The various type of oral sex practices are fellatio, cunnilingus and analingus. Oral sex is infrequently examined in research on adolescents; oral sex can transmit oral, respiratory, and genital pathogens. Oral health has a direct impact on the transmission of infection; a cut in your mouth, bleeding gums, lip sores or broken skin increases chances of infection. Although oral sex is considered a low risk activity, it is important to use protection and safer sex precautions. There are various methods of preventing infection during oral sex such as physical barriers, health and medical issues, ethical issues and oral hygiene and dental issues. The lesions or unhealthy periodontal status of oral cavity accelerates the phenomenon of transmission of infections into the circulation. Thus consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex.

  11. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target.

    Directory of Open Access Journals (Sweden)

    Katharine S Dobb

    Full Text Available Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds.

  12. Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3.

    Science.gov (United States)

    Bøsling, Jacob; Poulsen, Susan M; Vester, Birte; Long, Katherine S

    2003-09-01

    The antibiotic tiamulin targets the 50S subunit of the bacterial ribosome and interacts at the peptidyl transferase center. Tiamulin-resistant Escherichia coli mutants were isolated in order to elucidate mechanisms of resistance to the drug. No mutations in the rRNA were selected as resistance determinants using a strain expressing only a plasmid-encoded rRNA operon. Selection in a strain with all seven chromosomal rRNA operons yielded a mutant with an A445G mutation in the gene coding for ribosomal protein L3, resulting in an Asn149Asp alteration. Complementation experiments and sequencing of transductants demonstrate that the mutation is responsible for the resistance phenotype. Chemical footprinting experiments show a reduced binding of tiamulin to mutant ribosomes. It is inferred that the L3 mutation, which points into the peptidyl transferase cleft, causes tiamulin resistance by alteration of the drug-binding site. This is the first report of a mechanism of resistance to tiamulin unveiled in molecular detail.

  13. Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state

    Energy Technology Data Exchange (ETDEWEB)

    Osterman, Ilya A.; Khabibullina, Nelli F.; Komarova, Ekaterina S.; Kasatsky, Pavel; Kartsev, Victor G.; Bogdanov, Alexey A.; Dontsova, Olga A.; Konevega, Andrey L.; Sergiev, Petr V.; Polikanov, Yury S. (InterBioScreen); (UIC); (MSU-Russia); (Kurchatov)

    2017-05-13

    The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.

  14. Glutathione Transferases Superfamily: Cold-Inducible Expression of Distinct GST Genes in Brassica oleracea

    Directory of Open Access Journals (Sweden)

    Harshavardhanan Vijayakumar

    2016-07-01

    Full Text Available Plants, as sessile organisms, can suffer serious growth and developmental consequences under cold stress conditions. Glutathione transferases (GSTs, EC 2.5.1.18 are ubiquitous and multifunctional conjugating proteins, which play a major role in stress responses by preventing oxidative damage by reactive oxygen species (ROS. Currently, understanding of their function(s during different biochemical and signaling pathways under cold stress condition remain unclear. In this study, using combined computational strategy, we identified 65 Brassica oleracea glutathione transferases (BoGST and characterized them based on evolutionary analysis into 11 classes. Inter-species and intra-species duplication was evident between BoGSTs and Arabidopsis GSTs. Based on localization analyses, we propose possible pathways in which GST genes are involved during cold stress. Further, expression analysis of the predicted putative functions for GST genes were investigated in two cold contrasting genotypes (cold tolerance and susceptible under cold condition, most of these genes were highly expressed at 6 h and 1 h in the cold tolerant (CT and cold susceptible (CS lines, respectively. Overall, BoGSTU19, BoGSTU24, BoGSTF10 are candidate genes highly expressed in B. oleracea. Further investigation of GST superfamily in B. oleracea will aid in understanding complex mechanism underlying cold tolerance in plants.

  15. The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function

    International Nuclear Information System (INIS)

    Achilonu, Ikechukwu; Gildenhuys, Samantha; Fisher, Loren; Burke, Jonathan; Fanucchi, Sylvia; Sewell, B. Trevor; Fernandes, Manuel; Dirr, Heini W.

    2010-01-01

    The role of a topologically conserved isoleucine in the structure of glutathione transferase was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The common fold shared by members of the glutathione-transferase (GST) family has a topologically conserved isoleucine residue at the N-terminus of helix 3 which is involved in the packing of helix 3 against two β-strands in domain 1. The role of the isoleucine residue in the structure, function and stability of GST was investigated by replacing the Ile71 residue in human GSTA1-1 by alanine or valine. The X-ray structures of the I71A and I71V mutants resolved at 1.75 and 2.51 Å, respectively, revealed that the mutations do not alter the overall structure of the protein compared with the wild type. Urea-induced equilibrium unfolding studies using circular dichroism and tryptophan fluorescence suggest that the mutation of Ile71 to alanine or valine reduces the stability of the protein. A functional assay with 1-chloro-2,4-dinitrobenzene shows that the mutation does not significantly alter the function of the protein relative to the wild type. Overall, the results suggest that conservation of the topologically conserved Ile71 maintains the structural stability of the protein but does not play a significant role in catalysis and substrate binding

  16. Changes in amino transferases and muscle proteins when treating pigmeat with ionising rays

    Energy Technology Data Exchange (ETDEWEB)

    Hamm, R; Hofmann, K; Gruenewald, T; Partmann, W [Bundesanstalt fuer Fleischforschung, Kulmbach (F.R. Germany). Inst. fuer Chemie und Physik; Bundesforschungsanstalt fuer Ernaehrung, Karlsruhe [F.R. Germany

    1975-01-01

    Slices of lean pigmeat were treated with electron beams doses of 0.2, 1.0 and 5.0 Mrad. Low irradiation doses led to an increase in the activity of aspartate amino transferase (GOT) and alanin amino transferase (GPT) in the tissue generally and in the sarcoplasm (juice expressed from the muscle). 5 Mrad caused a great reduction in the activity of GOT and GPT in the tissue and the sarcoplasm. It seems doubtful whether this inactivation is due to a destruction of enzyme sulphhydryl groups. Irradiating with 5 Mrad resulted in partial release of the mitochondrial GOT isozyme (GOTsub(M)) into the sarcoplasm. This indicates damage to the mitochondrial membranes by ionising radiation. Irradiating the pigmeat increased the pH of the tissue and lowered its water binding ability (increase in drip). Up to a dose of 1 Mrad the solubility of the sarcoplasmic proteins was not definitely affected, but 5 Mrad caused a considerable drop in protein solubility. Surprisingly a dose of even 5 Mrad did not change the total number of sulphhydryl groups present in the tissue. Sephadex thin layer electrophoresis showed that at 0.2 Mrad there was a drastic decrease in the myosin band and an increase in peptide fragments of low molecular weight, whilst actin was little changed.

  17. Changes in amino transferases and muscle proteins when treating pigmeat with ionising rays

    International Nuclear Information System (INIS)

    Hamm, R.; Hofmann, K.; Gruenewald, T.; Partmann, W.

    1975-01-01

    Slices of lean pigmeat were treated with electron beams doses of 0.2, 1.0 and 5.0 Mrad. Low irradiation doses led to an increase in the activity of aspartate amino transferase (GOT) and alanin amino transferase (GPT) in the tissue generally and in the sarcoplasm (juice expressed from the muscle). 5 Mrad caused a great reduction in the activity of GOT and GPT in the tissue and the sarcoplasm. It seems doubtful whether this inactivation is due to a destruction of enzyme sulphhydryl groups. Irradiating with 5 Mrad resulted in partial release of the mitochondrial GOT isozyme (GOTsub(M)) into the sarcoplasm. This indicates damage to the mitochondrial membranes by ionising radiation. Irradiating the pigmeat increased the pH of the tissue and lowered its water binding ability (increase in drip). Up to a dose of 1 Mrad the solubility of the sarcoplasmic proteins was not definitely affected, but 5 Mrad caused a considerable drop in protein solubility. Surprisingly a dose of even 5 Mrad did not change the total number of sulphhydryl groups present in the tissue. Sephadex thin layer electrophoresis showed that at 0.2 Mrad there was a drastic decrease in the myosin band and an increase in peptide fragments of low molecular weight, whilst actin was little changed. (orig.) [de

  18. Epidermal growth factor regulation of glutathione S-transferase gene expression in the rat is mediated by class Pi glutathione S-transferase enhancer I.

    Science.gov (United States)

    Matsumoto, M; Imagawa, M; Aoki, Y

    2000-07-01

    Using chloramphenicol acetyltransferase assays we showed that epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and 3,3',4,4',5-pentachlorobiphenyl (PenCB) induce class Pi glutathione S-transferase (GSTP1) in primary cultured rat liver parenchymal cells. GSTP1 enhancer I (GPEI), which is required for the stimulation of GSTP1 expression by PenCB, also mediates EGF and TGF alpha stimulation of GSTP1 gene expression. However, hepatocyte growth factor and insulin did not stimulate GPEI-mediated gene expression. On the other hand, the antioxidant reagents butylhydroxyanisole and t-butylhydroquinone, stimulated GPEI-mediated gene expression, but the level of GSTP1 mRNA was not elevated. Our observations suggest that EGF and TGF alpha induce GSTP1 by the same signal transduction pathway as PenCB. Since the sequence of GPEI is similar to that of the antioxidant responsive element (ARE), some factors which bind to ARE might play a role in GPEI-mediated gene expression.

  19. O-GlcNAcylation in oral squamous cell carcinoma.

    Science.gov (United States)

    Kongkaew, Tassaporn; Aung, Win Pa Pa; Supanchart, Chayarop; Makeudom, Anupong; Langsa-Ard, Sarawat; Sastraruji, Thanapat; Chaiyarit, Ponlatham; Krisanaprakornkit, Suttichai

    2018-03-01

    Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading. Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR tyr1173 , and anti-phosphorylated-Akt ser473 antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody. The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR tyr1173 and phosphorylated-Akt ser473 were significantly higher in OSCC than normal tissues (P O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR tyr1173 and phosphorylated-Akt ser473 (P O-GlcNAc or OGT were not determined to correlate with histological grading. Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Clinical implications of thymidylate synthetase, dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activity levels in colorectal carcinoma following radical resection and administration of adjuvant 5-FU chemotherapy

    International Nuclear Information System (INIS)

    Ishikawa, Masashi; Miyauchi, Takayuki; Kashiwagi, Yutaka

    2008-01-01

    A number of studies have investigated whether the activity levels of enzymes involved in 5-fluorouracil (5-FU) metabolism are prognostic factors for survival in patients with colorectal carcinoma. Most reports have examined thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD) in unresectable or metastatic cases, therefore it is unclear whether the activity of these enzymes is of prognostic value in colorectal cancer patients treated with radical resection and adjuvant chemotherapy with 5-FU. This study examined fresh frozen specimens of colorectal carcinoma from 40 patients who had undergone curative operation and were orally administered adjuvant tegafur/uracil (UFT) chemotherapy. TS, DPD and orotate phosphoribosyl transferase (OPRT) activities were assayed in cancer tissue and adjacent normal tissue and their association with clinicopathological variables was investigated. In addition, the relationships between TS, DPD and OPRT activities and patient survival were examined to determine whether any of these enzymes could be useful prognostic factors. While there was no clear relationship between pathological findings and TS or DPD activity, OPRT activity was significantly lower in tumors with lymph node metastasis than in tumors lacking lymph node metastasis. Postoperative survival was significantly better in the groups with low TS activity and/or high OPRT activity. TS and OPRT activity levels in tumor tissue may be important prognostic factors for survival in Dukes' B and C colorectal carcinoma with radical resection and adjuvant chemotherapy with UFT

  1. Reviewing Hit Discovery Literature for Difficult Targets: Glutathione Transferase Omega-1 as an Example.

    Science.gov (United States)

    Xie, Yiyue; Dahlin, Jayme L; Oakley, Aaron J; Casarotto, Marco G; Board, Philip G; Baell, Jonathan B

    2018-05-10

    Early stage drug discovery reporting on relatively new or difficult targets is often associated with insufficient hit triage. Literature reviews of such targets seldom delve into the detail required to critically analyze the associated screening hits reported. Here we take the enzyme glutathione transferase omega-1 (GSTO1-1) as an example of a relatively difficult target and review the associated literature involving small-molecule inhibitors. As part of this process we deliberately pay closer-than-usual attention to assay interference and hit quality aspects. We believe this Perspective will be a useful guide for future development of GSTO1-1 inhibitors, as well serving as a template for future review formats of new or difficult targets.

  2. Response of Glutathione and Glutathione S-transferase in Rice Seedlings Exposed to Cadmium Stress

    Directory of Open Access Journals (Sweden)

    Chun-hua ZHANG

    2008-03-01

    Full Text Available A hydroponic culture experiment was done to investigate the effect of Cd stress on glutathione content (GSH and glutathione S-transferase (GST, EC 2.5.1.18 activity in rice seedlings. The rice growth was severely inhibited when Cd level in the solution was higher than 10 mg/L. In rice shoots, GSH content and GST activity increased with the increasing Cd level, while in roots, GST was obviously inhibited by Cd treatments. Compared with shoots, the rice roots had higher GSH content and GST activity, indicating the ability of Cd detoxification was much higher in roots than in shoots. There was a significant correlation between Cd level and GSH content or GST activity, suggesting that both parameters may be used as biomarkers of Cd stress in rice.

  3. Differential roles of tau class glutathione S-transferases in oxidative stress

    DEFF Research Database (Denmark)

    Kilili, Kimiti G; Atanassova, Neli; Vardanyan, Alla

    2004-01-01

    The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous...... Tau class GSTs, which readily form heterodimers between them and BI-GST. All six LeGSTUs were found to be able to protect yeast cells from prooxidant-induced cell death. The efficiency of each LeGSTU was prooxidant-specific, indicating a different role for each LeGSTU in the oxidative stress......-response mechanism. The prooxidant protective effect of all six proteins was suppressed in the absence of YAP1, a transcription factor that regulates hydroperoxide homeostasis in Saccharomyces cerevisiae, suggesting a role for the LeGSTUs in the context of the YAP1-dependent stress-responsive machinery...

  4. Phi Class of Glutathione S-transferase Gene Superfamily Widely Exists in Nonplant Taxonomic Groups.

    Science.gov (United States)

    Munyampundu, Jean-Pierre; Xu, You-Ping; Cai, Xin-Zhong

    2016-01-01

    Glutathione S-transferases (GSTs) constitute a superfamily of enzymes involved in detoxification of noxious compounds and protection against oxidative damage. GST class Phi (GSTF), one of the important classes of plant GSTs, has long been considered as plant specific but was recently found in basidiomycete fungi. However, the range of nonplant taxonomic groups containing GSTFs remains unknown. In this study, the distribution and phylogenetic relationships of nonplant GSTFs were investigated. We identified GSTFs in ascomycete fungi, myxobacteria, and protists Naegleria gruberi and Aureococcus anophagefferens. GSTF occurrence in these bacteria and protists correlated with their genome sizes and habitats. While this link was missing across ascomycetes, the distribution and abundance of GSTFs among ascomycete genomes could be associated with their lifestyles to some extent. Sequence comparison, gene structure, and phylogenetic analyses indicated divergence among nonplant GSTFs, suggesting polyphyletic origins during evolution. Furthermore, in silico prediction of functional partners suggested functional diversification among nonplant GSTFs.

  5. Echinococcus granulosus: Evidence of a heterodimeric glutathione transferase built up by phylogenetically distant subunits.

    Science.gov (United States)

    Arbildi, Paula; La-Rocca, Silvana; Lopez, Veronica; Da-Costa, Natalia; Fernandez, Veronica

    2017-01-01

    In the cestode parasite Echinococcus granulosus, three phylogenetically distant cytosolic glutathione transferases (GSTs) (EgGST1, 2 and 3) were identified. Interestingly, the C-terminal domains of EgGST3 and EgGST2 but not EgGST1, exhibit all amino acids involved in Sigma-class GST dimerization. Here, we provide evidence indicating that EgGST2 and EgGST3 naturally form a heterodimeric structure (EgGST2-3), and also we report the enzymatic activity of the recombinant heterodimer. EgGST2-3 might display novel properties able to influence the infection establishment. This is the first report of a stable heterodimeric GST built up by phylogenetically distant subunits. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Isolation and purification of glutathione S-transferases from Brachionus plicatilis and B. calyciflorus (Rotifera).

    Science.gov (United States)

    Bowman, B P; Snell, T W; Cochrane, B J

    1990-01-01

    1. The enzyme glutathione S-transferase (GST), a critical element in xenobiotic metabolism, was isolated from the marine rotifer Brachionus plicatilis and its freshwater congener B. calyciflorus. 2. In B. plicatilis, GST comprised 4.2% of cytosolic protein and was present as three separate isozymes with mol. wts 30,000, 31,400 and 33,700. Specific activity of crude homogenates was 56 nmol min-1 mg-1 protein, while that of affinity chromatography purified GST was 1850. 3. In B. calyciflorus, GST was present as two isozymes with mol. wts of 26,300 and 28,500, representing 1.0% of cytosolic protein. Crude GST specific activity was 1750 nmol min-1 mg-1 protein and purified was 72,400. 4. Rotifer GSTs are unusual because they are monomers whereas all other animals thus far investigated posses dimeric GSTs.

  7. Nuclear translocation of glutathione transferase omega is a progression marker in Barrett's esophagus

    DEFF Research Database (Denmark)

    Piaggi, Simona; Marchi, Santino; Ciancia, Eugenio

    2009-01-01

    Barrett's esophagus (BE) represents a major risk factor for esophageal adenocarcinoma (AC). For this reason, patients with BE are subjected to a systematic endoscopic surveillance to detect initial evolution towards non-invasive neoplasia (NiN) and cancer, that eventually occurs only in a small......-S-transferase-omega 1 could be involved in the stress response of human cells playing a role in the cancer progression of Barrett's esophagus. Its immunohistochemical detection could represent a useful tool in the grading of Barrett's disease.......N in BE and to understand the mechanisms of the progression from BE to AC. We investigated the expression and subcellular localization of GSTO1 in biopsies from patients with BE and in human cancer cell lines subjected to heath shock treatment. A selective nuclear localisation of GSTO1 was found in 16/16 biopsies with low...

  8. Glutathione transferases are structural and functional outliers in the thioredoxin fold.

    Science.gov (United States)

    Atkinson, Holly J; Babbitt, Patricia C

    2009-11-24

    Glutathione transferases (GSTs) are ubiquitous scavengers of toxic compounds that fall, structurally and functionally, within the thioredoxin fold suprafamily. The fundamental catalytic capability of GSTs is catalysis of the nucleophilic addition or substitution of glutathione at electrophilic centers in a wide range of small electrophilic compounds. While specific GSTs have been studied in detail, little else is known about the structural and functional relationships between different groupings of GSTs. Through a global analysis of sequence and structural similarity, it was determined that variation in the binding of glutathione between the two major subgroups of cytosolic (soluble) GSTs results in a different mode of glutathione activation. Additionally, the convergent features of glutathione binding between cytosolic GSTs and mitochondrial GST kappa are described. The identification of these structural and functional themes helps to illuminate some of the fundamental contributions of the thioredoxin fold to catalysis in the GSTs and clarify how the thioredoxin fold can be modified to enable new functions.

  9. Glutathione-binding site of a bombyx mori theta-class glutathione transferase.

    Directory of Open Access Journals (Sweden)

    M D Tofazzal Hossain

    Full Text Available The glutathione transferase (GST superfamily plays key roles in the detoxification of various xenobiotics. Here, we report the isolation and characterization of a silkworm protein belonging to a previously reported theta-class GST family. The enzyme (bmGSTT catalyzes the reaction of glutathione with 1-chloro-2,4-dinitrobenzene, 1,2-epoxy-3-(4-nitrophenoxy-propane, and 4-nitrophenethyl bromide. Mutagenesis of highly conserved residues in the catalytic site revealed that Glu66 and Ser67 are important for enzymatic function. These results provide insights into the catalysis of glutathione conjugation in silkworm by bmGSTT and into the metabolism of exogenous chemical agents.

  10. Identification of Protein-Protein Interactions with Glutathione-S-Transferase (GST) Fusion Proteins.

    Science.gov (United States)

    Einarson, Margret B; Pugacheva, Elena N; Orlinick, Jason R

    2007-08-01

    INTRODUCTIONGlutathione-S-transferase (GST) fusion proteins have had a wide range of applications since their introduction as tools for synthesis of recombinant proteins in bacteria. GST was originally selected as a fusion moiety because of several desirable properties. First and foremost, when expressed in bacteria alone, or as a fusion, GST is not sequestered in inclusion bodies (in contrast to previous fusion protein systems). Second, GST can be affinity-purified without denaturation because it binds to immobilized glutathione, which provides the basis for simple purification. Consequently, GST fusion proteins are routinely used for antibody generation and purification, protein-protein interaction studies, and biochemical analysis. This article describes the use of GST fusion proteins as probes for the identification of protein-protein interactions.

  11. Serum glutathione transferase does not respond to indole-3-carbinol: A pilot study

    Directory of Open Access Journals (Sweden)

    Daniel R McGrath

    2010-05-01

    Full Text Available Daniel R McGrath1, Hamid Frydoonfar2, Joshua J Hunt3, Chris J Dunkley3, Allan D Spigelman41Ipswich Hospital, Ipswich, UK; 2Hunter Pathology Service, New South Wales; 3Royal Newcastle Centre, Newcastle; 4St Vincent’s Clinical School, Sydney, AustraliaBackground: Despite the well recognized protective effect of cruciferous vegetables against various cancers, including human colorectal cancers, little is known about how this effect is conferred. It is thought that some phytochemicals found only in these vegetables confer the protection. These compounds include the glucosinolates, of which indole-3-carbinol is one. They are known to induce carcinogen-metabolizing (phase II enzymes, including the glutathione S-transferase (GST family. Other effects in humans are not well documented. We wished to assess the effect of indole-3-carbinol on GST enzymes.Methods: We carried out a placebo-controlled human volunteer study. All patients were given 400 mg daily of indole-3-carbinol for three months, followed by placebo. Serum samples were tested for the GSTM1 genotype by polymerase chain reaction. Serum GST levels were assessed using enzyme-linked immunosorbent assay and Western Blot methodologies.Results: Forty-nine volunteers completed the study. GSTM1 genotypes were obtained for all but two volunteers. A slightly greater proportion of volunteers were GSTM1-positive, in keeping with the general population. GST was detected in all patients. Total GST level was not affected by indole-3-carbinol dosing compared with placebo. Although not statistically significant, the GSTM1 genotype affected the serum GST level response to indole-3-carbinol.Conclusion: Indole-3-carbinol does not alter total serum GST levels during prolonged dosing.Keywords: pilot study, colorectal cancer, glutathione transferase, human, indole-3-carbinol

  12. Antioxidant farnesylated hydroquinones from Ganoderma capense.

    Science.gov (United States)

    Peng, Xingrong; Li, Lei; Wang, Xia; Zhu, Guolei; Li, Zhongrong; Qiu, Minghua

    2016-06-01

    Phytochemical investigation of the fruiting bodies of Ganoderma capense led to isolation of eight aromatic meroterpenoids (1-8). Ganocapensins A and B (1, 2) possessed a thirteen-membered and a fourteen-membered ether rings, respectively. The structures of new isolates including absolute configuration were elucidated on the basis of extensive spectroscopic technologies and Mosher's method. All isolated compounds showed significant antioxidant effects with IC50 values ranging from 6.00±0.11 to 8.20±0.30μg/ml in the DPPH radical scavenging assay. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age X SNP interaction and Cardiometabolic Disease Associations

    NARCIS (Netherlands)

    Middelberg, R.P.S.; Benyamin, B.; de Moor, M.H.M.; Warrington, N.M.; Gordon, S.; Henders, A.K.; Medland, S.E.; Nyholt, DR; de Geus, E.J.C.; Hottenga, J.J.; Willemsen, G.; Beilin, L.J.; Mori, T.A.; Wright, M.J.; Heath, A.C.; Madden, P.A.F.; Boomsma, D.I.; Pennell, C.E.; Montgomery, G.W.; Martin, N.G.; Whitfield, J.B.

    2012-01-01

    Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in

  14. Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

    DEFF Research Database (Denmark)

    Palner, Mikael; McCormick, Patrick; Parkes, Jun

    2010-01-01

    R-[(11)C]-SKF 82957 is a high-affinity and potent dopamine D(1) receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, f...

  15. Glutathione S-transferase M1 and T1, CYP1A2-2467T/delT ...

    African Journals Online (AJOL)

    The present study investigated the impact of metabolic gene polymorphisms in modulating lung cancer risk susceptibility. Gene polymorphisms encoding Cytochrome 1A2 (CYP1A2) and Glutathione-S-transferases (GSTT1 and GSTM1) are involved in the bioactivation and detoxification of tobacco carcinogens and may ...

  16. Mapping important nucleotides in the peptidyl transferase centre of 23 S rRNA using a random mutagenesis approach

    DEFF Research Database (Denmark)

    Porse, B T; Garrett, R A

    1995-01-01

    Random mutations were generated in the lower half of the peptidyl transferase loop in domain V of 23 S rRNA from Escherichia coli using a polymerase chain reaction (PCR) approach, a rapid procedure for identifying mutants and a plasmid-based expression system. The effects of 21 single-site mutati...

  17. Cloning and characterization of a glutathione S-transferase homologue from the plant pathogenic fungus Botrytis cinerea

    NARCIS (Netherlands)

    Prins, T.W.; Wagemakers, L.; Schouten, A.; Kan, van J.A.L.

    2000-01-01

    A gene was cloned from Botrytis cinerea that encodes a protein homologous to glutathione S-transferase (GST). The gene, denominated Bcgst1, is present in a single copy and represents the first example of such a gene from a filamentous fungus. The biochemical function of GSTs is to conjugate toxic

  18. The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome.

    Science.gov (United States)

    Poulsen, S M; Karlsson, M; Johansson, L B; Vester, B

    2001-09-01

    The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs are strong inhibitors of peptidyl transferase and interact with domain V of 23S RNA, giving clear chemical footprints at nucleotides A2058-9, U2506 and U2584-5. Most of these nucleotides are highly conserved phylogenetically and functionally important, and all of them are at or near the peptidyl transferase centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer.

  19. The interdomain flexible linker of the polypeptide GalNAc transferases dictates their long-range glycosylation preferences

    DEFF Research Database (Denmark)

    Rivas, Matilde De Las; Lira-Navarrete, Erandi; Daniel, Earnest James Paul

    2017-01-01

    The polypeptide GalNAc-transferases (GalNAc-Ts), that initiate mucin-type O-glycosylation, consist of a catalytic and a lectin domain connected by a flexible linker. In addition to recognizing polypeptide sequence, the GalNAc-Ts exhibit unique long-range N- A nd/or C-terminal prior glycosylation ...

  20. Transmutation of human glutathione transferase A2-2 with peroxidase activity into an efficient steroid isomerase.

    Science.gov (United States)

    Pettersson, Par L; Johansson, Ann-Sofie; Mannervik, Bengt

    2002-08-16

    A major goal in protein engineering is the tailor-making of enzymes for specified chemical reactions. Successful attempts have frequently been based on directed molecular evolution involving libraries of random mutants in which variants with desired properties were identified. For the engineering of enzymes with novel functions, it would be of great value if the necessary changes of the active site could be predicted and implemented. Such attempts based on the comparison of similar structures with different substrate selectivities have previously met with limited success. However, the present work shows that the knowledge-based redesign restricted to substrate-binding residues in human glutathione transferase A2-2 can introduce high steroid double-bond isomerase activity into the enzyme originally characterized by glutathione peroxidase activity. Both the catalytic center activity (k(cat)) and catalytic efficiency (k(cat)/K(m)) match the values of the naturally evolved glutathione transferase A3-3, the most active steroid isomerase known in human tissues. The substrate selectivity of the mutated glutathione transferase was changed 7000-fold by five point mutations. This example demonstrates the functional plasticity of the glutathione transferase scaffold as well as the potential of rational active-site directed mutagenesis as a complement to DNA shuffling and other stochastic methods for the redesign of proteins with novel functions.

  1. The association of alcohol intake with gamma-glutamyl transferase (GGT) levels: Evidence for correlated genetic effects

    NARCIS (Netherlands)

    van Beek, J.H.D.A.; de Moor, M.H.M.; Geels, L.M.; Sinke, M.R.T.; de Geus, E.J.C.; Lubke, G.H.; Kluft, C.; Neuteboom, J.; Vink, J.M.; Willemsen, G.; Boomsma, D.I.

    2014-01-01

    Background: Blood levels of gamma-glutamyl transferase (GGT) are used as a marker for (heavy) alcohol use. The role of GGT in the anti-oxidant defense mechanism that is part of normal metabolism supposes a causal effect of alcohol intake on GGT. However, there is variability in the response of GGT

  2. Cooperation of terminal deoxynucleotidyl transferase with DNA polymerase α in the replication of ultraviolet-irradiated DNA

    International Nuclear Information System (INIS)

    Yoshida, S.; Masaki, S.; Nakamura, H.; Morita, T.

    1981-01-01

    The amount of DNA synthesis in vitro with the ultraviolet-irradiated poly(dT).oligo(rA) template initiators catalysed by DNA polymerase α (Masaki, S. and Yoshida, S., Biochim. Biophys. Acta 521, 74-88) decreased with the dose of ultraviolet-irradiation. The ultraviolet irradiation to the template, however, did not affect the rate of incorporation of incorrect deoxynucleotides into the newly synthesized poly(dA). The addition of terminal deoxynucleotidyl transferase to this system enhanced the DNA synthesis to a level which is comparable to that of the control and it concomitantly increased the incorporation of the mismatched deoxynucleotide into the newly synthesized poly(dA) strands. On the other hand, with an unirradiated template initiator, the misincorporation was only slightly enhanced by the addition of terminal deoxynucleotidyl transferase. The sizes of newly synthesized DNA measured by the sedimentation velocities were found to be smaller with the ultraviolet-irradiated templates but they increased to the control level with the addition of terminal deoxynucleotidyl transferase to the systems. These results suggest that terminal deoxynucleotidyl transferase can help DNA polymerase α to bypass thymine dimers in vitro by the formation of mismatched regions at the positions opposite to pyrimidine dimers on the template. (Auth.)

  3. Mutations in N-acetylglucosamine (O-GlcNAc) transferase in patients with X-linked intellectual disability

    NARCIS (Netherlands)

    Willems, A.P.; Gundogdu, M.; Kempers, M.J.E.; Giltay, J.C.; Pfundt, R.P.; Elferink, M.; Loza, B.F.; Fuijkschot, J.; Ferenbach, A.T.; Gassen, K.L. van; Aalten, D.M.F. van; Lefeber, D.J.

    2017-01-01

    N-Acetylglucosamine (O-GlcNAc) transferase (OGT) regulates protein O-GlcNAcylation, an essential and dynamic post-translational modification. The O-GlcNAc modification is present on numerous nuclear and cytosolic proteins and has been implicated in essential cellular functions such as signaling and

  4. Function and phylogeny of bacterial butyryl-CoA:acetate transferases and their diversity in the proximal colon of swine

    Science.gov (United States)

    Studying the host-associated butyrate-producing bacterial community is important because butyrate is essential for colonic homeostasis and gut health. Previous research has identified the butyryl-coA:acetate transferase (2.3.8.3) as a the main gene for butyrate production in intestinal ecosystems; h...

  5. Oral contraceptives induced hepatotoxicity

    OpenAIRE

    B. Akshaya Srikanth; V. Manisree

    2013-01-01

    Oral Contraceptives are the pharmacological agents used to prevent pregnancy. These are divided as the combined and progestogen methods and are administered orally, transdermally, systemically and via vaginal route. All these methods contain both oestrogen and progestogen. Vigorous usage of oral contraceptives and anabolic steroids as associated with cholestasis, vascular lesions and hepatic neoplasm. Benign hepatic neoplasms are clearly associated with oral contraceptives. In this article we...

  6. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  7. Oral vaccination of fish

    NARCIS (Netherlands)

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen

  8. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... to detect oral cancer during your routine dental examinations. Don't risk it. Perform an oral cancer ... oral cancer self-exam each month. An oral examination is performed using a bright light and a ...

  9. Contribution of liver mitochondrial membrane-bound glutathione transferase to mitochondrial permeability transition pores

    International Nuclear Information System (INIS)

    Hossain, Quazi Sohel; Ulziikhishig, Enkhbaatar; Lee, Kang Kwang; Yamamoto, Hideyuki; Aniya, Yoko

    2009-01-01

    We recently reported that the glutathione transferase in rat liver mitochondrial membranes (mtMGST1) is activated by S-glutathionylation and the activated mtMGST1 contributes to the mitochondrial permeability transition (MPT) pore and cytochrome c release from mitochondria [Lee, K.K., Shimoji, M., Quazi, S.H., Sunakawa, H., Aniya, Y., 2008. Novel function of glutathione transferase in rat liver mitochondrial membrane: role for cytochrome c release from mitochondria. Toxcol. Appl. Pharmacol. 232, 109-118]. In the present study we investigated the effect of reactive oxygen species (ROS), generator gallic acid (GA) and GST inhibitors on mtMGST1 and the MPT. When rat liver mitochondria were incubated with GA, mtMGST1 activity was increased to about 3 fold and the increase was inhibited with antioxidant enzymes and singlet oxygen quenchers including 1,4-diazabicyclo [2,2,2] octane (DABCO). GA-mediated mtMGST1 activation was prevented by GST inhibitors such as tannic acid, hematin, and cibacron blue and also by cyclosporin A (CsA). In addition, GA induced the mitochondrial swelling which was also inhibited by GST inhibitors, but not by MPT inhibitors CsA, ADP, and bongkrekic acid. GA also released cytochrome c from the mitochondria which was inhibited completely by DABCO, moderately by GST inhibitors, and somewhat by CsA. Ca 2+ -mediated mitochondrial swelling and cytochrome c release were inhibited by MPT inhibitors but not by GST inhibitors. When the outer mitochondrial membrane was isolated after treatment of mitochondria with GA, mtMGST1 activity was markedly increased and oligomer/aggregate of mtMGST1 was observed. These results indicate that mtMGST1 in the outer mitochondrial membrane is activated by GA through thiol oxidation leading to protein oligomerization/aggregation, which may contribute to the formation of ROS-mediated, CsA-insensitive MPT pore, suggesting a novel mechanism for regulation of the MPT by mtMGST1

  10. Inhibition of the recombinant cattle tick Rhipicephalus (Boophilus) annulatus glutathione S-transferase.

    Science.gov (United States)

    Guneidy, Rasha A; Shahein, Yasser E; Abouelella, Amira M K; Zaki, Eman R; Hamed, Ragaa R

    2014-09-01

    Rhipicephalus (Boophilus) annulatus is a bloodsucking ectoparasite that causes severe production losses in the cattle industry. This study aims to evaluate the in vitro effects of tannic acid, hematin (GST inhibitors) and different plant extracts (rich in tannic acid) on the activity of the recombinant glutathione S-transferase enzyme of the Egyptian cattle tick R. annulatus (rRaGST), in order to confirm their ability to inhibit the parasitic essential detoxification enzyme glutathione S-transferase. Extraction with 70% ethanol of Hibiscus cannabinus (kenaf flowers), Punica granatum (red and white pomegranate peel), Musa acuminata (banana peel) (Musaceae), Medicago sativa (alfalfa seeds), Tamarindus indicus (seed) and Cuminum cyminum (cumin seed) were used to assess: (i) inhibitory capacities of rRaGST and (ii) their phenolic and flavonoid contents. Ethanol extraction of red pomegranate peel contained the highest content of phenolic compounds (29.95mg gallic acid/g dry tissue) compared to the other studied plant extracts. The highest inhibition activities of rRaGST were obtained with kenaf and red pomegranate peel (P. granatum) extracts with IC50 values of 0.123 and 0.136mg dry tissue/ml, respectively. Tannic acid was the more effective inhibitor of rRaGST with an IC50 value equal to 4.57μM compared to delphinidine-HCl (IC50=14.9±3.1μM). Gossypol had a weak inhibitory effect (IC50=43.7μM), and caffeic acid had almost no effect on tick GST activity. The IC50 values qualify ethacrynic acid as a potent inhibitor of rRaGST activity (IC50=0.034μM). Cibacron blue and hematin showed a considerable inhibition effect on rRaGST activity, and their IC50 values were 0.13μM and 7.5μM, respectively. The activity of rRaGST was highest for CDNB (30.2μmol/min/mg protein). The enzyme had also a peroxidatic activity (the specific activity equals 26.5μmol/min/mg protein). Both tannic acid and hematin inhibited rRaGST activity non-competitively with respect to GSH and

  11. Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

    Energy Technology Data Exchange (ETDEWEB)

    Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas [UC Irvine, 2212 Natural Sciences I, Irvine, CA 92697 (United States); Goulding, Celia W., E-mail: celia.goulding@uci.edu [UC Irvine, 2212 Natural Sciences I, Irvine, CA 92697 (United States); UC Irvine, 2302 Natural Sciences I, Irvine, CA 92697 (United States)

    2014-04-01

    The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully

  12. Structural snapshots along the reaction pathway of Yersinia pestis RipA, a putative butyryl-CoA transferase

    International Nuclear Information System (INIS)

    Torres, Rodrigo; Lan, Benson; Latif, Yama; Chim, Nicholas; Goulding, Celia W.

    2014-01-01

    The crystal structures of Y. pestis RipA mutants were determined to provide insights into the CoA transferase reaction pathway. Yersinia pestis, the causative agent of bubonic plague, is able to survive in both extracellular and intracellular environments within the human host, although its intracellular survival within macrophages is poorly understood. A novel Y. pestis three-gene rip (required for intracellular proliferation) operon, and in particular ripA, has been shown to be essential for survival and replication in interferon γ-induced macrophages. RipA was previously characterized as a putative butyryl-CoA transferase proposed to yield butyrate, a known anti-inflammatory shown to lower macrophage-produced NO levels. RipA belongs to the family I CoA transferases, which share structural homology, a conserved catalytic glutamate which forms a covalent CoA-thioester intermediate and a flexible loop adjacent to the active site known as the G(V/I)G loop. Here, functional and structural analyses of several RipA mutants are presented in an effort to dissect the CoA transferase mechanism of RipA. In particular, E61V, M31G and F60M RipA mutants show increased butyryl-CoA transferase activities when compared with wild-type RipA. Furthermore, the X-ray crystal structures of E61V, M31G and F60M RipA mutants, when compared with the wild-type RipA structure, reveal important conformational changes orchestrated by a conserved acyl-group binding-pocket phenylalanine, Phe85, and the G(V/I)G loop. Binary structures of M31G RipA and F60M RipA with two distinct CoA substrate conformations are also presented. Taken together, these data provide CoA transferase reaction snapshots of an open apo RipA, a closed glutamyl-anhydride intermediate and an open CoA-thioester intermediate. Furthermore, biochemical analyses support essential roles for both the catalytic glutamate and the flexible G(V/I)G loop along the reaction pathway, although further research is required to fully

  13. Essentials of oral cancer.

    Science.gov (United States)

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators.

  14. Screening for oral cancer.

    Science.gov (United States)

    Jitender, Solanki; Sarika, Gupta; Varada, Hiremath R; Omprakash, Yadav; Mohsin, Khan

    2016-11-01

    Oral cancer is considered as a serious health problem resulting in high morbidity and mortality. Early detection and prevention play a key role in controlling the burden of oral cancer worldwide. The five-year survival rate of oral cancer still remains low and delayed diagnosis is considered as one of the major reasons. This increases the demand for oral screening. Currently, screening of oral cancer is largely based on visual examination. Various evidence strongly suggest the validity of visual inspection in reducing mortality in patients at risk for oral cancer. Simple visual examination is accompanied with adjunctive techniques for subjective interpretation of dysplastic changes. These include toluidine blue staining, brush biopsy, chemiluminescence and tissue autofluorescence. This review highlights the efficacy of various diagnostic methods in screening of oral cancer. © 2016 Old City Publishing, Inc.

  15. Expression profiling of selected glutathione transferase genes in Zea mays (L.) seedlings infested with cereal aphids.

    Science.gov (United States)

    Sytykiewicz, Hubert; Chrzanowski, Grzegorz; Czerniewicz, Paweł; Sprawka, Iwona; Łukasik, Iwona; Goławska, Sylwia; Sempruch, Cezary

    2014-01-01

    The purpose of this report was to evaluate the expression patterns of selected glutathione transferase genes (gst1, gst18, gst23 and gst24) in the tissues of two maize (Zea mays L.) varieties (relatively resistant Ambrozja and susceptible Tasty Sweet) that were colonized with oligophagous bird cherry-oat aphid (Rhopalosiphum padi L.) or monophagous grain aphid (Sitobion avenae L.). Simultaneously, insect-triggered generation of superoxide anion radicals (O2•-) in infested Z. mays plants was monitored. Quantified parameters were measured at 1, 2, 4, 8, 24, 48 and 72 h post-initial aphid infestation (hpi) in relation to the non-infested control seedlings. Significant increases in gst transcript amounts were recorded in aphid-stressed plants in comparison to the control seedlings. Maximal enhancement in the expression of the gst genes in aphid-attacked maize plants was found at 8 hpi (gst23) or 24 hpi (gst1, gst18 and gst24) compared to the control. Investigated Z. mays cultivars formed excessive superoxide anion radicals in response to insect treatments, and the highest overproduction of O2•- was noted 4 or 8 h after infestation, depending on the aphid treatment and maize genotype. Importantly, the Ambrozja variety could be characterized as having more profound increments in the levels of gst transcript abundance and O2•- generation in comparison with the Tasty Sweet genotype.

  16. In-vitro effect of flavonoids from Solidago canadensis extract on glutathione S-transferase.

    Science.gov (United States)

    Apáti, Pál; Houghton, Peter J; Kite, Geoffrey; Steventon, Glyn B; Kéry, Agnes

    2006-02-01

    Solidago canadensis is typical of a flavonoid-rich herb and the effect of an aqueous ethanol extract on glutathione-S-transferase (GST) activity using HepG2 cells was compared with those of the flavonol quercetin and its glycosides quercitrin and rutin, found as major constituents. The composition of the extract was determined by HPLC and rutin was found to be the major flavonoidal component of the extract. Total GST activity was assessed using 1-chloro-2,4-dinitrobenzene as a substrate. The glycosides rutin and quercitrin gave dose-dependent increases in GST activity, with a 50% and 24.5% increase at 250 mM, respectively, while the aglycone quercetin inhibited the enzyme by 30% at 250 mM. The total extract of the herb gave an overall dose-dependent increase, the fractions corresponding to the flavonoids showed activating effects while those containing caffeic acid derivatives were inhibitory. The activity observed corresponds to that reported for similar compounds in-vivo using rats, thus the HepG2 cell line could serve as a more satisfactory method of assessing the effects of extracts and compounds on GST.

  17. Terminal deoxynucleotidyl transferase in the diagnosis of leukemia and malignant lymphoma.

    Science.gov (United States)

    Kung, P C; Long, J C; McCaffrey, R P; Ratliff, R L; Harrison, T A; Baltimore, D

    1978-05-01

    Neoplastic cells from 253 patients with leukemia and 46 patients with malignant lymphoma were studied for the presence of terminal deoxynucleotidyl transferase (TdT) by biochemical and fluorescent antibody technics. TdT was detected in circulating blast cells from 73 of 77 patients with acute lymphoblastic leukemia, 24 of 72 patients with chronic myelogenous leukemia examined during the blastic phase of the disorder and in cell suspensions of lymph nodes from nine of nine patients with diffuse lymphoblastic lymphoma. Blast cells from six of 10 patients with acute undifferentiated leukemia were TdT positive, but the enzyme was found in only two of 55 patients with acute myeloblastic leukemia. TdT was not detected in other lymphocytic or granulocytic leukemias or in other types of malignant lymphomas. The fluorescent antibody assay for TdT permits rapid and specific identification of the enzyme in single cells. The TdT assay is clinically useful in confirming the diagnosis of acute lymphoblastic leukemia, evaluating patients with blastic chronic myelogenous leukemia, and distinguishing patients with lymphoblastic lymphoma, whose natural history includes rapid extranodal dissemination, from patients with other poorly differentiated malignant lymphomas.

  18. Lack of Ach1 CoA-Transferase Triggers Apoptosis and Decreases Chronological Lifespan in Yeast

    International Nuclear Information System (INIS)

    Orlandi, Ivan; Casatta, Nadia; Vai, Marina

    2012-01-01

    ACH1 encodes a mitochondrial enzyme of Saccharomyces cerevisiae endowed with CoA-transferase activity. It catalyzes the CoASH transfer from succinyl-CoA to acetate generating acetyl-CoA. It is known that ACH1 inactivation results in growth defects on media containing acetate as a sole carbon and energy source which are particularly severe at low pH. Here, we show that chronological aging ach1Δ cells which accumulate a high amount of extracellular acetic acid display a reduced chronological lifespan. The faster drop of cell survival is completely abrogated by alleviating the acid stress either by a calorie restricted regimen that prevents acetic acid production or by transferring chronologically aging mutant cells to water. Moreover, the short-lived phenotype of ach1Δ cells is accompanied by reactive oxygen species accumulation, severe mitochondrial damage, and an early insurgence of apoptosis. A similar pattern of endogenous severe oxidative stress is observed when ach1Δ cells are cultured using acetic acid as a carbon source under acidic conditions. On the whole, our data provide further evidence of the role of acetic acid as cell-extrinsic mediator of cell death during chronological aging and highlight a primary role of Ach1 enzymatic activity in acetic acid detoxification which is important for mitochondrial functionality.

  19. Serum γ-Glutamyl Transferase Is Inversely Associated with Bone Mineral Density Independently of Alcohol Consumption

    Directory of Open Access Journals (Sweden)

    Han Seok Choi

    2016-03-01

    Full Text Available Backgroundγ-Glutamyl transferase (GGT is a well-known marker of chronic alcohol consumption or hepatobiliary diseases. A number of studies have demonstrated that serum levels of GGT are independently associated with cardiovascular and metabolic disorders. The purpose of this study was to test if serum GGT levels are associated with bone mineral density (BMD in Korean adults.MethodsA total of 462 subjects (289 men and 173 women, who visited Severance Hospital for medical checkup, were included in this study. BMD was measured using dual energy X-ray absorptiometry. Cross-sectional association between serum GGT and BMD was evaluated.ResultsAs serum GGT levels increased from the lowest tertile (tertile 1 to the highest tertile (tertile 3, BMD decreased after adjusting for confounders such as age, body mass index, amount of alcohol consumed, smoking, regular exercise, postmenopausal state (in women, hypertension, diabetes mellitus, and hypercholesterolemia. A multiple linear regression analysis showed a negative association between log-transformed serum GGT levels and BMD. In a multiple logistic regression analysis, tertile 3 of serum GGT level was associated with an increased risk for low bone mass compared to tertile 1 (odds ratio, 2.271; 95% confidence interval, 1.340 to 3.850; P=0.002.ConclusionSerum GGT level was inversely associated with BMD in Korean adults. Further study is necessary to fully elucidate the mechanism of the inverse relationship.

  20. The dyad palindromic glutathione transferase P enhancer binds multiple factors including AP1.

    Science.gov (United States)

    Diccianni, M B; Imagawa, M; Muramatsu, M

    1992-10-11

    Glutathione Transferase P (GST-P) gene expression is dominantly regulated by an upstream enhancer (GPEI) consisting of a dyad of palindromically oriented imperfect TPA (12-O-tetradecanoyl-phorbol-13-acetate)-responsive elements (TRE). GPEI is active in AP1-lacking F9 cells as well in AP1-containing HeLa cells. Despite GPEI's similarity to a TRE, c-jun co-transfection has only a minimal effect on transactivation. Antisense c-jun and c-fos co-transfection experiments further demonstrate the lack of a role for AP1 in GPEI mediated trans-activation in F9 cells, although endogenously present AP1 can influence GPEI in HeLa cells. Co-transfection of delta fosB with c-jun, which forms an inactive c-Jun/delta FosB heterodimer that binds TRE sequences, inhibits GPEI-mediated transcription in AP1-lacking F9 cells as well as AP1-containing HeLa cells. These data suggest novel factor(s) other than AP1 are influencing GPEI. Binding studies reveal multiple nucleoproteins bind to GPEI. These factors are likely responsible for the high level of GPEI-mediated transcription observed in the absence of AP1 and during hepatocarcinogenesis.

  1. Expression Profiling of Selected Glutathione Transferase Genes in Zea mays (L.) Seedlings Infested with Cereal Aphids

    Science.gov (United States)

    Sytykiewicz, Hubert; Chrzanowski, Grzegorz; Czerniewicz, Paweł; Sprawka, Iwona; Łukasik, Iwona; Goławska, Sylwia; Sempruch, Cezary

    2014-01-01

    The purpose of this report was to evaluate the expression patterns of selected glutathione transferase genes (gst1, gst18, gst23 and gst24) in the tissues of two maize (Zea mays L.) varieties (relatively resistant Ambrozja and susceptible Tasty Sweet) that were colonized with oligophagous bird cherry-oat aphid (Rhopalosiphum padi L.) or monophagous grain aphid (Sitobion avenae L.). Simultaneously, insect-triggered generation of superoxide anion radicals (O2 •−) in infested Z. mays plants was monitored. Quantified parameters were measured at 1, 2, 4, 8, 24, 48 and 72 h post-initial aphid infestation (hpi) in relation to the non-infested control seedlings. Significant increases in gst transcript amounts were recorded in aphid-stressed plants in comparison to the control seedlings. Maximal enhancement in the expression of the gst genes in aphid-attacked maize plants was found at 8 hpi (gst23) or 24 hpi (gst1, gst18 and gst24) compared to the control. Investigated Z. mays cultivars formed excessive superoxide anion radicals in response to insect treatments, and the highest overproduction of O2 •− was noted 4 or 8 h after infestation, depending on the aphid treatment and maize genotype. Importantly, the Ambrozja variety could be characterized as having more profound increments in the levels of gst transcript abundance and O2 •− generation in comparison with the Tasty Sweet genotype. PMID:25365518

  2. Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients

    Directory of Open Access Journals (Sweden)

    Pandey Sanjay

    2012-01-01

    Full Text Available BACKGROUND: Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. Due to the different pathophysiology of anemia in thalassemia and sickle cell disease, there are significant differences in the pathophysiology of iron overload and iron-related complications in these disorders. OBJECTIVE: The aim of this study was to estimate the frequency of the GSTM1 and GSTT1 genotypes in sickle cell disease patients and their effect on iron status. METHODS: Forty sickle cell anemia and sixty sickle ß-thalassemia patients and 100 controls were evaluated to determine the frequency of GST gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography with DNA extraction by the phenol-chloroform method. The GST null genotype was determined using multiplex polymerase chain reaction and serum ferritin was measured using an ELISA kit. Statistical analysis was by EpiInfo and GraphPad statistics software. RESULTS: An increased frequency of the GSTT1 null genotype (p-value = 0.05 was seen in the patients. The mean serum ferritin level was higher in patients with the GST genotypes than in controls; this was statistically significant for all genotypes except GSTM1, however the higher levels of serum ferritin were due to blood transfusions in patients. CONCLUSION: GST deletions do not play a direct role in iron overload of sickle cell patients.

  3. Characterization and evolutionary implications of the triad Asp-Xxx-Glu in group II phosphopantetheinyl transferases.

    Science.gov (United States)

    Wang, Yue-Yue; Li, Yu-Dong; Liu, Jian-Bo; Ran, Xin-Xin; Guo, Yuan-Yang; Ren, Ni-Ni; Chen, Xin; Jiang, Hui; Li, Yong-Quan

    2014-01-01

    Phosphopantetheinyl transferases (PPTases), which play an essential role in both primary and secondary metabolism, are magnesium binding enzymes. In this study, we characterized the magnesium binding residues of all known group II PPTases by biochemical and evolutionary analysis. Our results suggested that group II PPTases could be classified into two subgroups, two-magnesium-binding-residue-PPTases containing the triad Asp-Xxx-Glu and three-magnesium-binding-residue-PPTases containing the triad Asp-Glu-Glu. Mutations of two three-magnesium-binding-residue-PPTases and one two-magnesium-binding-residue-PPTase indicate that the first and the third residues in the triads are essential to activities; the second residues in the triads are non-essential. Although variations of the second residues in the triad Asp-Xxx-Glu exist throughout the whole phylogenetic tree, the second residues are conserved in animals, plants, algae, and most prokaryotes, respectively. Evolutionary analysis suggests that: the animal group II PPTases may originate from one common ancestor; the plant two-magnesium-binding-residue-PPTases may originate from one common ancestor; the plant three-magnesium-binding-residue-PPTases may derive from horizontal gene transfer from prokaryotes.

  4. Characterization of glutathione S-transferase and its immunodiagnostic potential for detecting Taenia multiceps.

    Science.gov (United States)

    Sun, Ying; Wang, Yu; Huang, Xing; Gu, Xiaobing; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

    2017-08-15

    Taenia multiceps is a widespread zoonotic tapeworm parasite which infects cloven-hoofed animals around the world. Animal infection with Coenurus cerebralis, the coenurus larvae of T. multiceps (Tm), is often fatal, which is a major cause of economic losses in stockbreeding. This study amplified the glutathione S-transferase (GST) gene from the total RNA of C. cerebralis. The resulting protein, Tm-GST, consisted of 201 amino acids, and had a predicted molecular mass of 23.1kDa. Its amino acid sequence shares 77.61% similarity with Echinococcus granulosus GST. Recombinant Tm-GST (rTm-GST) was expressed in Escherichia coli. The protein reacted with serum from goats infected with T. multiceps. Immunofluorescence signals indicated that Tm-GST was largely localized in the parenchymatous area of adult T. multiceps; in addition, it was also apparent in the coenurus. An enzyme-linked immunosorbent assay based on rTm-GST showed specificity of 92.8% (13/14) and sensitivity of 90% (18/20) in detecting anti-GST antibodies in serum from naturally infected animals. This study suggests that Tm-GST has the potential to be used as a diagnostic antigen for Coenurosis. Copyright © 2017. Published by Elsevier B.V.

  5. A glutathione S-transferase gene associated with antioxidant properties isolated from Apis cerana cerana

    Science.gov (United States)

    Liu, Shuchang; Liu, Feng; Jia, Haihong; Yan, Yan; Wang, Hongfang; Guo, Xingqi; Xu, Baohua

    2016-06-01

    Glutathione S-transferases (GSTs) are an important family of multifunctional enzymes in aerobic organisms. They play a crucial role in the detoxification of exogenous compounds, especially insecticides, and protection against oxidative stress. Most previous studies of GSTs in insects have largely focused on their role in insecticide resistance. Here, we isolated a theta class GST gene designated AccGSTT1 from Apis cerana cerana and aimed to explore its antioxidant and antibacterial attributes. Analyses of homology and phylogenetic relationships suggested that the predicted amino acid sequence of AccGSTT1 shares a high level of identity with the other hymenopteran GSTs and that it was conserved during evolution. Quantitative real-time PCR showed that AccGSTT1 is most highly expressed in adult stages and that the expression profile of this gene is significantly altered in response to various abiotic stresses. These results were confirmed using western blot analysis. Additionally, a disc diffusion assay showed that a recombinant AccGSTT1 protein may be roughly capable of inhibiting bacterial growth and that it reduces the resistance of Escherichia coli cells to multiple adverse stresses. Taken together, these data indicate that AccGSTT1 may play an important role in antioxidant processes under adverse stress conditions.

  6. Glutathione S-Transferases: Role in Combating Abiotic Stresses Including Arsenic Detoxification in Plants

    Directory of Open Access Journals (Sweden)

    Smita Kumar

    2018-06-01

    Full Text Available Arsenic (As, naturally occurring metalloid and a potential hazardous material, is found in low concentrations in the environment and emerges from natural sources and anthropogenic activities. The presence of As in ground water, which is used for irrigation, is a matter of great concern since it affects crop productivity and contaminates food chain. In plants, As alters various metabolic pathways in cells including the interaction of substrates/enzymes with the sulfhydryl groups of proteins and the replacement of phosphate in ATP for energy. In addition, As stimulates the generation of free radicals and reactive oxygen species (ROS, resulting in oxidative stress. Glutathione S-transferases (GSTs quench reactive molecules with the addition of glutathione (GSH and protect the cell from oxidative damage. GSTs are a multigene family of isozymes, known to catalyze the conjugation of GSH to miscellany of electrophilic and hydrophobic substrates. GSTs have been reported to be associated with plant developmental processes and are responsive to multitude of stressors. In past, several studies suggested involvement of plant GST gene family in As response due to the requirement of sulfur and GSH in the detoxification of this toxic metalloid. This review provides updated information about the role of GSTs in abiotic and biotic stresses with an emphasis on As uptake, metabolism, and detoxification in plants. Further, the genetic manipulations that helped in enhancing the understanding of the function of GSTs in abiotic stress response and heavy metal detoxification has been reviewed.

  7. The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?

    Science.gov (United States)

    Levine, Zebulon G; Walker, Suzanne

    2016-06-02

    O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.

  8. Solution Structural Studies of GTP:Adenosylcobinamide-Phosphateguanylyl Transferase (CobY from Methanocaldococcus jannaschii.

    Directory of Open Access Journals (Sweden)

    Kiran K Singarapu

    Full Text Available GTP:adenosylcobinamide-phosphate (AdoCbi-P guanylyl transferase (CobY is an enzyme that transfers the GMP moiety of GTP to AdoCbi yielding AdoCbi-GDP in the late steps of the assembly of Ado-cobamides in archaea. The failure of repeated attempts to crystallize ligand-free (apo CobY prompted us to explore its 3D structure by solution NMR spectroscopy. As reported here, the solution structure has a mixed α/β fold consisting of seven β-strands and five α-helices, which is very similar to a Rossmann fold. Titration of apo-CobY with GTP resulted in large changes in amide proton chemical shifts that indicated major structural perturbations upon complex formation. However, the CobY:GTP complex as followed by 1H-15N HSQC spectra was found to be unstable over time: GTP hydrolyzed and the protein converted slowly to a species with an NMR spectrum similar to that of apo-CobY. The variant CobYG153D, whose GTP complex was studied by X-ray crystallography, yielded NMR spectra similar to those of wild-type CobY in both its apo- state and in complex with GTP. The CobYG153D:GTP complex was also found to be unstable over time.

  9. [Synthesis of vitamin K2 by isopentenyl transferase NovA in Pichia pastoris Gpn12].

    Science.gov (United States)

    Wu, Xihua; Li, Zhemin; Liu, Hui; Wang, Peng; Wang, Li; Fang, Xue; Sun, Xiaowen; Ni, Wenfeng; Yang, Qiang; Zheng, Zhiming; Zhao, Genhai

    2018-01-25

    The effect of methanol addition on the heterologous expression of isoprenyl transferase NovQ was studied in Pichia pastoris Gpn12, with menadione and isopentenol as precursors to catalyze vitamin K2 (MK-3) synthesis. The expression of NovQ increased by 36% when 2% methanol was added every 24 h. The influence of initial pH, temperature, methanol addition, precursors (menadione, isopentenol) addition, catalytic time and cetyltrimethyl-ammonium bromide (CTAB) addition were explored in the P. pastoris whole-cell catalytic synthesis process of MK-3 in shaking flask. Three significant factors were then studied by response surface method. The optimal catalytic conditions obtained were as follows: catalytic temperature 31.56 ℃, menadione 295.54 mg/L, catalytic time 15.87 h. Consistent with the response surface prediction results, the optimized yield of MK-3 reached 98.47 mg/L in shaking flask, 35% higher than that of the control group. On this basis, the production in a 30-L fermenter reached 189.67 mg/L when the cell catalyst of 220 g/L (dry weight) was used to catalyze the synthesis for 24 h. This method laid the foundation for the large-scale production of MK-3 by P. pastoris Gpn12.

  10. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis.

    Science.gov (United States)

    Anderson, N M; Li, D; Peng, H L; Laroche, F J F; Mansour, M R; Gjini, E; Aioub, M; Helman, D J; Roderick, J E; Cheng, T; Harrold, I; Samaha, Y; Meng, L; Amsterdam, A; Neuberg, D S; Denton, T T; Sanda, T; Kelliher, M A; Singh, A; Look, A T; Feng, H

    2016-06-01

    Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development. DLST is the E2 transferase of the α-ketoglutarate (α-KG) dehydrogenase complex (KGDHC), which converts α-KG to succinyl-CoA in the TCA cycle. RNAi knockdown of DLST led to decreased cell viability and induction of apoptosis in human T-ALL cell lines. Polar metabolomics profiling revealed that the TCA cycle was disrupted by DLST knockdown in human T-ALL cells, as demonstrated by an accumulation of α-KG and a decrease of succinyl-CoA. Addition of succinate, the downstream TCA cycle intermediate, to human T-ALL cells was sufficient to rescue defects in cell viability caused by DLST inactivation. Together, our studies uncovered an important role for DLST in MYC-mediated leukemogenesis and demonstrated the metabolic dependence of T-lymphoblasts on the TCA cycle, thus providing implications for targeted therapy.

  11. Corneal aldehyde dehydrogenase and glutathione S-transferase activity after excimer laser keratectomy in guinea pigs.

    Science.gov (United States)

    Bilgihan, K; Bilgihan, A; Hasanreisoğlu, B; Turkozkan, N

    1998-03-01

    The free radical balance of the eye may be changed by excimer laser keratectomy. Previous studies have demonstrated that excimer laser keratectomy increases the corneal temperature, decreases the superoxide dismutase activity of the aqueous, and induces lipid peroxidation in the superficial corneal stroma. Aldehyde dehydrogenase (ALDH) and glutathione S-transferase (GST) are known to play an important role in corneal metabolism, particularly in detoxification of aldehydes, which are generated from free radical reactions. In three groups of guinea pigs mechanical corneal de-epithelialisation was performed in group I, superficial corneal photoablation in group II, and deep corneal photoablation in group III, and the corneal ALDH and GST activities measured after 48 hours. The mean ALDH and GST activities of group I and II showed no differences compared with the controls (p > 0.05). The corneal ALDH activities were found to be significantly decreased (p < 0.05) and GST activities increased (p < 0.05) in group III. These results suggest that excimer laser treatment of high myopia may change the ALDH and GST activities, metabolism, and free radical balance of the cornea.

  12. Isozyme-specific fluorescent inhibitor of glutathione s-transferase omega 1.

    Science.gov (United States)

    Son, Junghyun; Lee, Jae-Jung; Lee, Jun-Seok; Schüller, Andreas; Chang, Young-Tae

    2010-05-21

    Recently, the glutathione S-transferase omega 1 (GSTO1) is suspected to be involved in certain cancers and neurodegenerative diseases. However, profound investigation on the pathological roles of GSTO1 has been hampered by the lack of specific methods to determine or modulate its activity in biological systems containing other isoforms with similar catalytic function. Here, we report a fluorescent compound that is able to inhibit and monitor the activity of GSTO1. We screened 43 fluorescent chemicals and found a compound (6) that binds specifically to the active site of GSTO1. We observed that compound 6 inhibits GSTO1 by covalent modification but spares other isoforms in HEK293 cells and demonstrated that compound 6 could report the activity of GSTO1 in NIH/3T3 or HEK293 cells by measuring the fluorescence intensity of the labeled amount of GSTO1 in SDS-PAGE. Compound 6 is a useful tool to study GSTO1, applicable as a specific inhibitor and an activity reporter.

  13. Identification and characterisation of multiple glutathione S-transferase genes from the diamondback moth, Plutella xylostella.

    Science.gov (United States)

    Chen, Xi'en; Zhang, Ya-lin

    2015-04-01

    The diamondback moth (DBM), Plutella xylostella, is one of the most harmful insect pests on crucifer crops worldwide. In this study, 19 cDNAs encoding glutathione S-transferases (GSTs) were identified from the genomic and transcriptomic database for DBM (KONAGAbase) and further characterized. Phylogenetic analysis showed that the 19 GSTs were classified into six different cytosolic classes, including four in delta, six in epsilon, three in omega, two in sigma, one in theta and one in zeta. Two GSTs were unclassified. RT-PCR analysis revealed that most GST genes were expressed in all developmental stages, with higher expression in the larval stages. Six DBM GSTs were expressed at the highest levels in the midgut tissue. Twelve purified recombinant GSTs showed varied enzymatic properties towards 1-chloro-2,4-dinitrobenzene and glutathione, whereas rPxGSTo2, rPxGSTz1 and rPxGSTu2 had no activity. Real-time quantitative PCR revealed that expression levels of the 19 DBM GST genes were varied and changed after exposure to acephate, indoxacarb, beta-cypermethrin and spinosad. PxGSTd3 was significantly overexpressed, while PxGSTe3 and PxGSTs2 were significantly downregulated by all four insecticide exposures. The changes in DBM GST gene expression levels exposed to different insecticides indicate that they may play individual roles in tolerance to insecticides and xenobiotics. © 2014 Society of Chemical Industry.

  14. Electrochemical DNA biosensor based on grafting-to mode of terminal deoxynucleoside transferase-mediated extension.

    Science.gov (United States)

    Chen, Jinyuan; Liu, Zhoujie; Peng, Huaping; Zheng, Yanjie; Lin, Zhen; Liu, Ailin; Chen, Wei; Lin, Xinhua

    2017-12-15

    Previously reported electrochemical DNA biosensors based on in-situ polymerization approach reveal that terminal deoxynucleoside transferase (TdTase) has good amplifying performance and promising application in the design of electrochemical DNA biosensor. However, this method, in which the background is significantly affected by the amount of TdTase, suffers from being easy to produce false positive result and poor stability. Herein, we firstly present a novel electrochemical DNA biosensor based on grafting-to mode of TdTase-mediated extension, in which DNA targets are polymerized in homogeneous solution and then hybridized with DNA probes on BSA-based DNA carrier platform. It is surprising to find that the background in the grafting-to mode of TdTase-based electrochemical DNA biosensor have little interference from the employed TdTase. Most importantly, the proposed electrochemical DNA biosensor shows greatly improved detection performance over the in-situ polymerization approach-based electrochemical DNA biosensor. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Relation of serum γ-glutamyl transferase activity with copper in an adult population.

    Science.gov (United States)

    Peng, You-Fan; Wang, Chun-Fang; Pan, Guo-Gang

    2017-10-26

    The aim of this study was to evaluate the relationship between serum γ-glutamyl transferase (γ-GGT) activity and serum copper in an adult population. We analyzed 281 adult subjects who regularly attended the physical examination center at the Affiliated Hospital of Youjiang Medical University for Nationalities. The demographic and laboratory data of the participants were divided into two groups according to the median of serum γ-GGT activity. Serum copper concentrations in individuals with higher γ-GGT levels were significantly increased compared with those with lower γ-GGT concentrations (9.9±2.41 vs. 11.2±3.36 μmol/L, pcopper in all eligible subjects (r=0.198, p=0.001). Further, serum γ-GGT maintained a positive correlation with serum copper in both males and females (r=0.322, pcopper after adjusting for multiple potential confounders (b=0.464, p=0.001). This study suggests that serum γ-GGT activity is correlated with copper in the study population, indicating that serum γ-GGT may be a biomarker to evaluate serum copper levels in an adult population.

  16. Legionella shows a diverse secondary metabolism dependent on a broad spectrum Sfp-type phosphopantetheinyl transferase

    Directory of Open Access Journals (Sweden)

    Nicholas J. Tobias

    2016-11-01

    Full Text Available Several members of the genus Legionella cause Legionnaires’ disease, a potentially debilitating form of pneumonia. Studies frequently focus on the abundant number of virulence factors present in this genus. However, what is often overlooked is the role of secondary metabolites from Legionella. Following whole genome sequencing, we assembled and annotated the Legionella parisiensis DSM 19216 genome. Together with 14 other members of the Legionella, we performed comparative genomics and analysed the secondary metabolite potential of each strain. We found that Legionella contains a huge variety of biosynthetic gene clusters (BGCs that are potentially making a significant number of novel natural products with undefined function. Surprisingly, only a single Sfp-like phosphopantetheinyl transferase is found in all Legionella strains analyzed that might be responsible for the activation of all carrier proteins in primary (fatty acid biosynthesis and secondary metabolism (polyketide and non-ribosomal peptide synthesis. Using conserved active site motifs, we predict some novel compounds that are probably involved in cell-cell communication, differing to known communication systems. We identify several gene clusters, which may represent novel signaling mechanisms and demonstrate the natural product potential of Legionella.

  17. Glutathione S-transferase P influences redox and migration pathways in bone marrow.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available To interrogate why redox homeostasis and glutathione S-transferase P (GSTP are important in regulating bone marrow cell proliferation and migration, we isolated crude bone marrow, lineage negative and bone marrow derived-dendritic cells (BMDDCs from both wild type (WT and knockout (Gstp1/p2(-/- mice. Comparison of the two strains showed distinct thiol expression patterns. WT had higher baseline and reactive oxygen species-induced levels of S-glutathionylated proteins, some of which (sarco-endoplasmic reticulum Ca2(+-ATPase regulate Ca(2+ fluxes and subsequently influence proliferation and migration. Redox status is also a crucial determinant in the regulation of the chemokine system. CXCL12 chemotactic response was stronger in WT cells, with commensurate alterations in plasma membrane polarization/permeability and intracellular calcium fluxes; activities of the downstream kinases, ERK and Akt were also higher in WT. In addition, expression levels of the chemokine receptor CXCR4 and its associated phosphatase, SHP-2, were higher in WT. Inhibition of CXCR4 or SHP2 decreased the extent of CXCL12-induced migration in WT BMDDCs. The differential surface densities of CXCR4, SHP-2 and inositol trisphosphate receptor in WT and Gstp1/p2(-/- cells correlated with the differential CXCR4 functional activities, as measured by the extent of chemokine-induced directional migration and differences in intracellular signaling. These observed differences contribute to our understanding of how genetic ablation of GSTP causes different levels of myeloproliferation and migration [corrected

  18. Recognition and Detoxification of the Insecticide DDT by Drosophila melanogaster Glutathione S-Transferase D1

    Energy Technology Data Exchange (ETDEWEB)

    Low, Wai Yee; Feil, Susanne C.; Ng, Hooi Ling; Gorman, Michael A.; Morton, Craig J.; Pyke, James; McConville, Malcolm J.; Bieri, Michael; Mok, Yee-Foong; Robin, Charles; Gooley, Paul R.; Parker, Michael W.; Batterham, Philip (SVIMR-A); (Melbourne)

    2010-06-14

    GSTD1 is one of several insect glutathione S-transferases capable of metabolizing the insecticide DDT. Here we use crystallography and NMR to elucidate the binding of DDT and glutathione to GSTD1. The crystal structure of Drosophila melanogaster GSTD1 has been determined to 1.1 {angstrom} resolution, which reveals that the enzyme adopts the canonical GST fold but with a partially occluded active site caused by the packing of a C-terminal helix against one wall of the binding site for substrates. This helix would need to unwind or be displaced to enable catalysis. When the C-terminal helix is removed from the model of the crystal structure, DDT can be computationally docked into the active site in an orientation favoring catalysis. Two-dimensional {sup 1}H,{sup 15}N heteronuclear single-quantum coherence NMR experiments of GSTD1 indicate that conformational changes occur upon glutathione and DDT binding and the residues that broaden upon DDT binding support the predicted binding site. We also show that the ancestral GSTD1 is likely to have possessed DDT dehydrochlorinase activity because both GSTD1 from D. melanogaster and its sibling species, Drosophila simulans, have this activity.

  19. Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

    Directory of Open Access Journals (Sweden)

    Michela Pasello

    2011-01-01

    Full Text Available Recent studies have indicated that targeting glutathione-S-transferase (GST isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthiohexanol (NBDHEX has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST. NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

  20. Terminal deoxynucleotidyl transferase activity in the regenerating thymus of X-irradiated mice

    International Nuclear Information System (INIS)

    Daculsi, R.; Astier, T.; Legrand, E.; Duplan, J.F.

    1982-01-01

    The distribution of terminal deoyxnucleotidyl transferase (TdT) enzyme activity (EU per 10 8 cells) between peaks I and II was followed for a period of 42 days in regenerating thymus of lethally irradiated (9 Gy) C3H mice restored with 10 6 (C3H x AKR) F1 bone marrow cells. The detection of Thy-1.1 and Thy-1.2 surface antigens allowed for the discrimination between host and donor cells, and the main subpopulations of thymic cells were characterized by their sensitivity to H-2sup(k) antiserum and to dexamethazone. Two peaks of TdT activity could be detected on phosphocellulose chromatographic separation. The distribution of TdT activity between these two peaks was followed during the two periods of thymic endo- and exoregeneration. Peak I TdT activity was closely correlated with the variation in the percentage of the high H-2 population. Peak II activity was mostly related to low H-2 cells. The per cell content of both peak I and peak II activities exceeded the norm in rapidly expanding populations. Finally between days 10 and 14 the TdT activity of the endoregenerating population was apparently not different from that of the exoregenerating population between days 14 and 22. (Auth.)

  1. Oral biopsy: Oral pathologist′s perspective

    Directory of Open Access Journals (Sweden)

    K L Kumaraswamy

    2012-01-01

    Full Text Available Many oral lesions may need to be diagnosed by removing a sample of tissue from the oral cavity. Biopsy is widely used in the medical field, but the practice is not quite widespread in dental practice. As oral pathologists, we have found many artifacts in the tissue specimen because of poor biopsy technique or handling, which has led to diagnostic pitfalls and misery to both the patient and the clinician. This article aims at alerting the clinicians about the clinical faults arising preoperatively, intraoperatively and postoperatively while dealing with oral biopsy that may affect the histological assessment of the tissue and, therefore, the diagnosis. It also reviews the different techniques, precautions and special considerations necessary for specific lesions.

  2. The pleuromutilin drugs tiamulin and valnemulin bind to the RNA at the peptidyl transferase centre on the ribosome

    DEFF Research Database (Denmark)

    Poulsen, S M; Karlsson, M; Johansson, L B

    2001-01-01

    The pleuromutilin antibiotic derivatives, tiamulin and valnemulin, inhibit protein synthesis by binding to the 50S ribosomal subunit of bacteria. The action and binding site of tiamulin and valnemulin was further characterized on Escherichia coli ribosomes. It was revealed that these drugs...... centre and have been associated with binding of several antibiotics. Competitive footprinting shows that tiamulin and valnemulin can bind concurrently with the macrolide erythromycin but compete with the macrolide carbomycin, which is a peptidyl transferase inhibitor. We infer from these and previous...... results that tiamulin and valnemulin interact with the rRNA in the peptidyl transferase slot on the ribosomes in which they prevent the correct positioning of the CCA-ends of tRNAs for peptide transfer....

  3. A model to environmental monitoring based on glutathione-S-transferase activity and branchial lesions in catfish

    Science.gov (United States)

    Neta, Raimunda Nonata Fortes Carvalho; Torres, Audalio Rebelo

    2017-11-01

    In this work, we validate the glutathione-S-transferase and branchial lesions as biomarkers in catfish Sciades herzbergii to obtain a predictive model of the environmental impact effects in a harbor of Brazil. The catfish were sampled from a port known to be contaminated with heavy metals and organic compounds and from a natural reserve in São Marcos Bay, Maranhão. Two biomarkers, hepatic glutathione S-transferase (GST) activity and branchial lesions were analyzed. The values for GST activity were modeled with the occurrence of branchial lesions by fitting a third order polynomial. Results from the mathematical model indicate that GST activity has a strong polynomial relationship with the occurrence of branchial lesions in both the wet and the dry seasons, but only at the polluted port site. Our mathematic model indicates that when the GST ceases to act, serious branchial lesions are observed in the catfish of the contaminated port area.

  4. Glutathione S-Transferase of Brown Planthoppers (Nilaparvata lugens) Is Essential for Their Adaptation to Gramine-Containing Host Plants

    OpenAIRE

    Sun, Xiao-Qin; Zhang, Mao-Xin; Yu, Jing-Ya; Jin, Yu; Ling, Bing; Du, Jin-Ping; Li, Gui-Hua; Qin, Qing-Ming; Cai, Qing-Nian

    2013-01-01

    Plants have evolved complex processes to ward off attacks by insects. In parallel, insects have evolved mechanisms to thwart these plant defenses. To gain insight into mechanisms that mediate this arms race between plants and herbivorous insects, we investigated the interactions between gramine, a toxin synthesized by plants of the family Gramineae, and glutathione S transferase (GST), an enzyme found in insects that is known to detoxify xenobiotics. Here, we demonstrate that rice (Oryza sati...

  5. The activity of glutathione S-transferase in hepatopancreas of Procambarus clarkii: seasonal variations and the influence of environmental pollutants.

    Science.gov (United States)

    Nies, E; Almar, M M; Hermenegildo, C; Monsalve, E; Romero, F J

    1991-01-01

    1. The glutathione S-transferase activity in hepatopancreas of the American red crayfish Procambarus clarkii after 15 days' acclimatization in tap water aquaria was measured in specimens collected monthly for a whole year, and shows seasonal variation. 2. Previous data on the environmental pollution of Lake Albufera suggest a possible correlation with the activity tested in the different seasons of the year considering the results of non-acclimatized animals.

  6. β(1,3-glucanosyl-transferase activity is essential for cell wall integrity and viability of Schizosaccharomyces pombe.

    Directory of Open Access Journals (Sweden)

    María de Medina-Redondo

    Full Text Available BACKGROUND: The formation of the cell wall in Schizosaccharomyces pombe requires the coordinated activity of enzymes involved in the biosynthesis and modification of β-glucans. The β(1,3-glucan synthase complex synthesizes linear β(1,3-glucans, which remain unorganized until they are cross-linked to other β(1,3-glucans and other cell wall components. Transferases of the GH72 family play important roles in cell wall assembly and its rearrangement in Saccharomyces cerevisiae and Aspergillus fumigatus. Four genes encoding β(1,3-glucanosyl-transferases -gas1(+, gas2(+, gas4(+ and gas5(+- are present in S. pombe, although their function has not been analyzed. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report the characterization of the catalytic activity of gas1p, gas2p and gas5p together with studies directed to understand their function during vegetative growth. From the functional point of view, gas1p is essential for cell integrity and viability during vegetative growth, since gas1Δ mutants can only grow in osmotically supported media, while gas2p and gas5p play a minor role in cell wall construction. From the biochemical point of view, all of them display β(1,3-glucanosyl-transferase activity, although they differ in their specificity for substrate length, cleavage point and product size. In light of all the above, together with the differences in expression profiles during the life cycle, the S. pombe GH72 proteins may accomplish complementary, non-overlapping functions in fission yeast. CONCLUSIONS/SIGNIFICANCE: We conclude that β(1,3-glucanosyl-transferase activity is essential for viability in fission yeast, being required to maintain cell integrity during vegetative growth.

  7. Meat consumption, N-acetyl transferase 1 and 2 polymorphism and risk of breast cancer, in Danish postmenopausal women

    DEFF Research Database (Denmark)

    Egeberg, Rikke; Olsen, Anja; Autrup, Herman

    2008-01-01

    The aim of this study was to investigate whether polymorphisms in N-acetyl transferase 1 and 2 modify the association between meat consumption and risk of breast cancer. A nested case-control study was conducted among 24697 postmenopausal women included in the 'Diet, Cancer and Health' cohort study...... (1993-2000). Three hundred and seventy-eight breast cancer cases were identified and matched to 378 controls. The incidence rate ratio (95% confidence interval) for breast cancer was 1.09 (1.02-1.17) for total meat, 1.15 (1.01-1.31) for red meat and 1.23 (1.04-1.45) for processed meat per 25 g daily...... total meat intake and red meat intake and breast cancer risk were confined to intermediate/fast N-acetyl transferase 2 acetylators (P-interaction=0.03 and 0.04). Our findings support an association between meat consumption and breast cancer risk and that N-acetyl transferase 2 polymorphism has...

  8. Structures of a putative ζ-class glutathione S-transferase from the pathogenic fungus Coccidioides immitis

    International Nuclear Information System (INIS)

    Edwards, Thomas E.; Bryan, Cassie M.; Leibly, David J.; Dieterich, Shellie H.; Abendroth, Jan; Sankaran, Banumathi; Sivam, Dhileep; Staker, Bart L.; Van Voorhis, Wesley C.; Myler, Peter J.; Stewart, Lance J.

    2011-01-01

    The pathogenic fungus C. immitis causes coccidioidomycosis, a potentially fatal disease. Here, apo and glutathione-bound crystal structures of a previously uncharacterized protein from C. immitis that appears to be a ζ-class glutathione S-transferase are presented. Coccidioides immitis is a pathogenic fungus populating the southwestern United States and is a causative agent of coccidioidomycosis, sometimes referred to as Valley Fever. Although the genome of this fungus has been sequenced, many operons are not properly annotated. Crystal structures are presented for a putative uncharacterized protein that shares sequence similarity with ζ-class glutathione S-transferases (GSTs) in both apo and glutathione-bound forms. The apo structure reveals a nonsymmetric homodimer with each protomer comprising two subdomains: a C-terminal helical domain and an N-terminal thioredoxin-like domain that is common to all GSTs. Half-site binding is observed in the glutathione-bound form. Considerable movement of some components of the active site relative to the glutathione-free form was observed, indicating an induced-fit mechanism for cofactor binding. The sequence homology, structure and half-site occupancy imply that the protein is a ζ-class glutathione S-transferase, a maleylacetoacetate isomerase (MAAI)

  9. Oral manifestations of lupus.

    Science.gov (United States)

    Menzies, S; O'Shea, F; Galvin, S; Wynne, B

    2018-02-01

    Mucosal involvement is commonly seen in patients with lupus; however, oral examination is often forgotten. Squamous cell carcinoma arising within oral lupoid plaques has been described, emphasizing the importance of identifying and treating oral lupus. We undertook a retrospective single-centre study looking at oral findings in patients attending our multidisciplinary lupus clinic between January 2015 and April 2016. A total of 42 patients were included. The majority of patients were female (88%) and had a diagnosis of discoid lupus erythematosus (62%). Half of the patients had positive oral findings, 26% had no oral examination documented, and 24% had documented normal oral examinations. Our findings suggest that oral pathology is common in this cohort of patients. Regular oral examination is warranted to identify oral lupus and provide treatment. Associated diseases such as Sjogren's syndrome may also be identified. Patients should be encouraged to see their general dental practitioners on a regular basis for mucosal review. Any persistent ulcer that fails to respond to treatment or hard lump needs urgent histopathological evaluation to exclude malignant transformation to squamous cell carcinoma.

  10. Neuroantibodies (NAB) in African-American Children: Associations with Gender, Glutathione-S-Transferase (GST)Pi Polymorphisms (SNP) and Heavy Metals

    Science.gov (United States)

    CONTACT (NAME ONLY): Hassan El-Fawal Abstract Details PRESENTATION TYPE: Platform or Poster CURRENT CATEGORY: Neurodegenerative Disease | Biomarkers | Neurotoxicity, Metals KEYWORDS: Autoantibodies, Glutathione-S-Transferase, DATE/TIME LAST MODIFIED: DATE/TIME SUBMITTED: Abs...

  11. Evaluation of antioxidant and antimicrobial activity of seaweed ( Sargassum sp.) extract: A study on inhibition of glutathione-S-transferase Activity

    Digital Repository Service at National Institute of Oceanography (India)

    Patra, J.K.; Rath, S.K.; Jena, K.B.; Rathod, V.K.; Thatoi, H.

    In the present study, the free radical scavenging potentials (DPPH radical and hydroxyl radical), inhibition of lipid peroxidation, and glutathione-S-transferase and antimicrobial properties of Sargassum sp. extract were investigated. The tested...

  12. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  13. Oral microbiota and cancer

    OpenAIRE

    Meurman, Jukka H.

    2010-01-01

    Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the...

  14. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Conklin, Daniel J., E-mail: dj.conklin@louisville.edu [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Merchant, Michael L. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Division of Nephrology, Department of Medicine, University of Louisville, Louisville, KY 40292 (United States); Prough, Russell A. [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States); Williams, Jessica D. [University of Cincinnati College of Medicine, Internal Medicine, Cincinnati, OH 45267 (United States); Prabhu, Sumanth D. [Division of Cardiovascular Disease, University of Alabama-Birmingham, Birmingham, AL 35294 (United States); Bhatnagar, Aruni [Diabetes and Obesity Center, University of Louisville, Louisville, KY 40292 (United States); Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40292 (United States); Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY 40292 (United States)

    2015-06-01

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  15. Glutathione S-transferase P protects against cyclophosphamide-induced cardiotoxicity in mice

    International Nuclear Information System (INIS)

    Conklin, Daniel J.; Haberzettl, Petra; Jagatheesan, Ganapathy; Baba, Shahid; Merchant, Michael L.; Prough, Russell A.; Williams, Jessica D.; Prabhu, Sumanth D.; Bhatnagar, Aruni

    2015-01-01

    High-dose chemotherapy regimens using cyclophosphamide (CY) are frequently associated with cardiotoxicity that could lead to myocyte damage and congestive heart failure. However, the mechanisms regulating the cardiotoxic effects of CY remain unclear. Because CY is converted to an unsaturated aldehyde acrolein, a toxic, reactive CY metabolite that induces extensive protein modification and myocardial injury, we examined the role of glutathione S-transferase P (GSTP), an acrolein-metabolizing enzyme, in CY cardiotoxicity in wild-type (WT) and GSTP-null mice. Treatment with CY (100–300 mg/kg) increased plasma levels of creatine kinase-MB isoform (CK·MB) and heart-to-body weight ratio to a significantly greater extent in GSTP-null than WT mice. In addition to modest yet significant echocardiographic changes following acute CY-treatment, GSTP insufficiency was associated with greater phosphorylation of c-Jun and p38 as well as greater accumulation of albumin and protein–acrolein adducts in the heart. Mass spectrometric analysis revealed likely prominent modification of albumin, kallikrein-1-related peptidase, myoglobin and transgelin-2 by acrolein in the hearts of CY-treated mice. Treatment with acrolein (low dose, 1–5 mg/kg) also led to increased heart-to-body weight ratio and myocardial contractility changes. Acrolein induced similar hypotension in GSTP-null and WT mice. GSTP-null mice also were more susceptible than WT mice to mortality associated with high-dose acrolein (10–20 mg/kg). Collectively, these results suggest that CY cardiotoxicity is regulated, in part, by GSTP, which prevents CY toxicity by detoxifying acrolein. Thus, humans with low cardiac GSTP levels or polymorphic forms of GSTP with low acrolein-metabolizing capacity may be more sensitive to CY toxicity. - Graphical abstract: Cyclophosphamide (CY) treatment results in P450-mediated metabolic formation of phosphoramide mustard and acrolein (3-propenal). Acrolein is either metabolized and

  16. The poplar phi class glutathione transferase: expression, activity and structure of GSTF1

    Directory of Open Access Journals (Sweden)

    Henri ePégeot

    2014-12-01

    Full Text Available Glutathione transferases (GSTs constitute a superfamily of enzymes with essential roles in cellular detoxification and secondary metabolism in plants as in other organisms. Several plant GSTs, including those of the Phi class (GSTFs, require a conserved catalytic serine residue to perform glutathione (GSH-conjugation reactions. Genomic analyses revealed that terrestrial plants have around 10 GSTFs, 8 in the Populus trichocarpa genome, but their physiological functions and substrates are mostly unknown. Transcript expression analyses showed a predominant expression of all genes both in reproductive (female flowers, fruits, floral buds and vegetative organs (leaves, petioles. Here, we show that the recombinant poplar GSTF1 (PttGSTF1 possesses peroxidase activity towards cumene hydroperoxide and GSH-conjugation activity towards model substrates such as 2,4-dinitrochlorobenzene, benzyl and phenetyl isothiocyanate, 4-nitrophenyl butyrate and 4-hydroxy-2-nonenal but interestingly not on previously identified GSTF-class substrates. In accordance to analytical gel filtration data, crystal structure of PttGSTF1 showed a canonical dimeric organization with bound GSH or MES molecules. The structure of these protein-substrate complexes allowed delineating the residues contributing to both the G and H sites that form the active site cavity. In sum, the presence of GSTF1 transcripts and proteins in most poplar organs especially those rich in secondary metabolites such as flowers and fruits, together with its GSH-conjugation activity and its documented stress-responsive expression suggest that its function is associated with the catalytic transformation of metabolites and/or peroxide removal rather than with ligandin properties as previously reported for other GSTFs.

  17. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide.

    Directory of Open Access Journals (Sweden)

    Alexandra Audemard-Verger

    Full Text Available To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs in lupus nephritis (LN treated with cyclophosphamide (CYC. CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST.We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR was defined as proteinuria ≤0.33g/day and serum creatinine ≤124 µmol/l. Partial remission (PR was defined as proteinuria ≤1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline.Most patients were women (84% and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile→105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile→105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR (OR = 5.01 95% CI [1.02-24.51] and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]. No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed.This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

  18. Glutathione-supported arsenate reduction coupled to arsenolysis catalyzed by ornithine carbamoyl transferase

    International Nuclear Information System (INIS)

    Nemeti, Balazs; Gregus, Zoltan

    2009-01-01

    Three cytosolic phosphorolytic/arsenolytic enzymes, (purine nucleoside phosphorylase [PNP], glycogen phosphorylase, glyceraldehyde-3-phosphate dehydrogenase) have been shown to mediate reduction of arsenate (AsV) to the more toxic arsenite (AsIII) in a thiol-dependent manner. With unknown mechanism, hepatic mitochondria also reduce AsV. Mitochondria possess ornithine carbamoyl transferase (OCT), which catalyzes phosphorolytic or arsenolytic citrulline cleavage; therefore, we examined if mitochondrial OCT facilitated AsV reduction in presence of glutathione. Isolated rat liver mitochondria were incubated with AsV, and AsIII formed was quantified. Glutathione-supplemented permeabilized or solubilized mitochondria reduced AsV. Citrulline (substrate for OCT-catalyzed arsenolysis) increased AsV reduction. The citrulline-stimulated AsV reduction was abolished by ornithine (OCT substrate inhibiting citrulline cleavage), phosphate (OCT substrate competing with AsV), and the OCT inhibitor norvaline or PALO, indicating that AsV reduction is coupled to OCT-catalyzed arsenolysis of citrulline. Corroborating this conclusion, purified bacterial OCT mediated AsV reduction in presence of citrulline and glutathione with similar responsiveness to these agents. In contrast, AsIII formation by intact mitochondria was unaffected by PALO and slightly stimulated by citrulline, ornithine, and norvaline, suggesting minimal role for OCT in AsV reduction in intact mitochondria. In addition to OCT, mitochondrial PNP can also mediate AsIII formation; however, its role in AsV reduction appears severely limited by purine nucleoside supply. Collectively, mitochondrial and bacterial OCT promote glutathione-dependent AsV reduction with coupled arsenolysis of citrulline, supporting the hypothesis that AsV reduction is mediated by phosphorolytic/arsenolytic enzymes. Nevertheless, because citrulline cleavage is disfavored physiologically, OCT may have little role in AsV reduction in vivo.

  19. The effect of chemical carcinogenesis on rat glutathione S-transferase P1 gene transcriptional regulation.

    Science.gov (United States)

    Liu, D; Liao, M; Zuo, J; Henner, W D; Fan, F

    2001-03-01

    To investigate mechanisms of rat glutathione S-transferase P1 gene (rGSTP1) expression regulation during chemical carcinogenesis. we studied enhancer elements located in the region between -2.5 kb to -2.2 kb. The region was upstream from the start site of transcription and was divided into two major fragments, GPEI and GPEII. The GPEII fragment was further divided into two smaller fragments, GPEII- I and GPEII-2. Using a luciferase reporter system, we identified a strong enhancer of GPEI and a weak enhancer of GPEII in HeLa and a rat hepatoma cell line CBRH79 19 cell. The enhancer of GPEII was located within the GPEII-I region. Chemical stimulation by glycidyl methatylate (GMA) and phorbol 12-o-tetradecanoate 13-acetate (TPA) analysis revealed that induction of rGSTP1 expression was mainly through GPEI. Although H2O2 could enhance GPEII enhancer activity, the enhancement is not mediated by the NF-kappaB factor that bound the NF-kappaB site in GPEII. Using electrophoretic mobility shift assays (EMSA) and the UV cross-linking assays, we found that HeLa and CBRH7919 cells had proteins that specifically bound GPEI core sequence and a 64 kDa protein that interacted with GPEII-1. The cells from normal rat liver did not express the binding proteins. Therefore, the trans-acting factors seem to be closely related to GPEI, GPEII enhancer activities and may play an important role in high expression of rGSTPI gene.

  20. Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells

    International Nuclear Information System (INIS)

    Scharmach, E.; Hessel, S.; Niemann, B.; Lampen, A.

    2009-01-01

    The human colon adenocarcinoma cell line Caco-2 is frequently used to study human intestinal metabolism and transport of xenobiotica. Previous studies have shown that both Caco-2 cells and human colon cells constitutively express the multigene family of detoxifying enzymes glutathione S-transferases (GSTs), particularly GST alpha and GST pi. GSTs may play a fundamental role in the molecular interplay between phase I, II enzymes and ABC-transporters. The gut fermentation product, butyrate, can modulate the potential for detoxification. The aim of this study was to investigate the basal expression of further cytosolic GSTs in Caco-2 cells during cell differentiation. In addition, a comparison was made with expression levels in MCF-7 and HepG2, two other cell types with barrier functions. Finally, the butyrate-mediated modulation of gene and protein expression was determined by real time PCR and western blot analysis. In Caco-2, gene and protein expression levels of GST alpha increased during cell differentiation. High levels of GSTO1 and GSTP1 were constantly expressed. No expression of GSTM5 and GSTT1 was detected. HepG2 expressed GSTO1 and MCF-7 GSTZ1 most intensively. No expression of GSTA5, GSTM5, or GSTP1 was detected in either cell. Incubation of Caco-2 cells with butyrate (5 mM) significantly induced GSTA1 and GSTM2 in proliferating Caco-2 cells. In differentiated cells, butyrate tended to increase GSTO1 and GSTP1. The results of this study show that a differentiation-dependent expression of GSTs in Caco-2 cells may reflect the in vivo situation and indicate the potential of butyrate to modify intestinal metabolism. GSTA1-A4 have been identified as good markers for cell differentiation. The Caco-2 cell line is a useful model for assessing the potential of food-related substances to modulate the GST expression pattern.

  1. Menadione stress in Saccharomyces cerevisiae strains deficient in the glutathione transferases.

    Science.gov (United States)

    Castro, F A V; Herdeiro, R S; Panek, A D; Eleutherio, E C A; Pereira, M D

    2007-02-01

    Using S. cerevisiae as a eukaryotic cell model we have analyzed the involvement of both glutathione transferase isoforms, Gtt1 and Gtt2, in constitutive resistance and adaptive response to menadione, a quinone which can exert its toxicity as redox cycling and/or electrophiles. The detoxification properties, of these enzymes, have also been analyzed by the appearance of S-conjugates in the media. Direct exposure to menadione (20 mM/60 min) showed to be lethal for cells deficient on both Gtt1 and Gtt2 isoforms. However, after pre-treatment with a low menadione concentration, cells deficient in Gtt2 displayed reduced ability to acquire tolerance when compared with the control and the Gtt1 deficient strains. Analyzing the toxic effects of menadione we observed that the gtt2 mutant showed no reduction in lipid peroxidation levels. Moreover, measuring the levels of intracellular oxidation during menadione stress we have shown that the increase of this oxidative stress parameter was due to the capacity menadione possesses in generating reactive oxygen species (ROS) and that both GSH and Gtt2 isoform were required to enhance ROS production. Furthermore, the efflux of the menadione-GSH conjugate, which is related with detoxification of xenobiotic pathways, was not detected in the gtt2 mutant. Taken together, these results suggest that acquisition of tolerance against stress generated by menadione and the process of detoxification through S-conjugates are dependent upon Gtt2 activity. This assessment was corroborated by the increase of GTT2 expression, and not of GTT1, after menadione treatment.

  2. Characterization and expression profiling of glutathione S-transferases in the diamondback moth, Plutella xylostella (L.).

    Science.gov (United States)

    You, Yanchun; Xie, Miao; Ren, Nana; Cheng, Xuemin; Li, Jianyu; Ma, Xiaoli; Zou, Minming; Vasseur, Liette; Gurr, Geoff M; You, Minsheng

    2015-03-05

    Glutathione S-transferases (GSTs) are multifunctional detoxification enzymes that play important roles in insects. The completion of several insect genome projects has enabled the identification and characterization of GST genes over recent years. This study presents a genome-wide investigation of the diamondback moth (DBM), Plutella xylostella, a species in which the GSTs are of special importance because this pest is highly resistant to many insecticides. A total of 22 putative cytosolic GSTs were identified from a published P. xylostella genome and grouped into 6 subclasses (with two unclassified). Delta, Epsilon and Omega GSTs were numerically superior with 5 genes for each of the subclasses. The resulting phylogenetic tree showed that the P. xylostella GSTs were all clustered into Lepidoptera-specific branches. Intron sites and phases as well as GSH binding sites were strongly conserved within each of the subclasses in the GSTs of P. xylostella. Transcriptome-, RNA-seq- and qRT-PCR-based analyses showed that the GST genes were developmental stage- and strain-specifically expressed. Most of the highly expressed genes in insecticide resistant strains were also predominantly expressed in the Malpighian tubules, midgut or epidermis. To date, this is the most comprehensive study on genome-wide identification, characterization and expression profiling of the GST family in P. xylostella. The diversified features and expression patterns of the GSTs are inferred to be associated with the capacity of this species to develop resistance to a wide range of pesticides and biological toxins. Our findings provide a base for functional research on specific GST genes, a better understanding of the evolution of insecticide resistance, and strategies for more sustainable management of the pest.

  3. Thermal- and urea-induced unfolding processes of glutathione S-transferase by molecular dynamics simulation.

    Science.gov (United States)

    Li, Jiahuang; Chen, Yuan; Yang, Jie; Hua, Zichun

    2015-05-01

    The Schistosoma juponicum 26 kDa glutathione S-transferase (sj26GST) consists of the N-terminal domain (N-domain), containing three alpha-helices (named H1-H3) and four anti-parallel beta-strands (S1-S4), and the C-terminal domain (C-domain), comprising five alpha-helices (named H4-H8). In present work, molecular dynamics simulations and fluorescence spectroscopic were used to gain insights into the unfolding process of sj26GST. The molecular dynamics simulations on sj26GST subunit both in water and in 8 M urea were carried out at 300 K, 400 K and 500 K, respectively. Spectroscopic measurements were employed to monitor structural changes. Molecular dynamics simulations of sj26GST subunit induced by urea and temperature showed that the initial unfolding step of sj26GST both in water and urea occurred on N-domain, involving the disruption of helices H2, H3 and strands S3 and S4, whereas H6 was the last region exposed to solution and was the last helix to unfold. Moreover, simulations analyses combining with fluorescence and circular dichroism spectra indicated that N-domain could not fold independent, suggesting that correct folding of N-domain depended on its interactions with C-domain. We further proposed that the folding of GSTs could begin with the hydrophobic collapse of C-domain whose H4, H5, H6 and H7 could move close to each other and form a hydrophobic core, especially H6 wrapped in the hydrophobic center and beginning spontaneous formation of the helix. S3, S4, H3, and H2 could form in the wake of the interaction between C-domain and N-domain. The paper can offer insights into the molecular mechanism of GSTs unfolding. © 2014 Wiley Periodicals, Inc.

  4. Glutathione S-transferase genotypes modify lung function decline in the general population: SAPALDIA cohort study

    Directory of Open Access Journals (Sweden)

    Ackermann-Liebrich Ursula

    2007-01-01

    Full Text Available Abstract Background Understanding the environmental and genetic risk factors of accelerated lung function decline in the general population is a first step in a prevention strategy against the worldwide increasing respiratory pathology of chronic obstructive pulmonary disease (COPD. Deficiency in antioxidative and detoxifying Glutathione S-transferase (GST gene has been associated with poorer lung function in children, smokers and patients with respiratory diseases. In the present study, we assessed whether low activity variants in GST genes are also associated with accelerated lung function decline in the general adult population. Methods We examined with multiple regression analysis the association of polymorphisms in GSTM1, GSTT1 and GSTP1 genes with annual decline in FEV1, FVC, and FEF25–75 during 11 years of follow-up in 4686 subjects of the prospective SAPALDIA cohort representative of the Swiss general population. Effect modification by smoking, gender, bronchial hyperresponisveness and age was studied. Results The associations of GST genotypes with FEV1, FVC, and FEF25–75 were comparable in direction, but most consistent for FEV1. GSTT1 homozygous gene deletion alone or in combination with GSTM1 homozygous gene deletion was associated with excess decline in FEV1 in men, but not women, irrespective of smoking status. The additional mean annual decline in FEV1 in men with GSTT1 and concurrent GSTM1 gene deletion was -8.3 ml/yr (95% confidence interval: -12.6 to -3.9 relative to men without these gene deletions. The GSTT1 effect on the FEV1 decline comparable to the observed difference in FEV1 decline between never and persistent smoking men. Effect modification by gender was statistically significant. Conclusion Our results suggest that genetic GSTT1 deficiency is a prevalent and strong determinant of accelerated lung function decline in the male general population.

  5. Enhanced tolerance and remediation of anthracene by transgenic tobacco plants expressing a fungal glutathione transferase gene

    Energy Technology Data Exchange (ETDEWEB)

    Dixit, Prachy; Mukherjee, Prasun K.; Sherkhane, Pramod D.; Kale, Sharad P. [Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Eapen, Susan, E-mail: eapenhome@yahoo.com [Nuclear Agriculture and Biotechnology Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2011-08-15

    Highlights: {yields} Transgenic plants expressing a TvGST gene were tested for tolerance, uptake and degradation of anthracene. {yields} Transgenic plants were more tolerant to anthracene and take up more anthracene from soil and solutions compared to control plants. {yields} Using in vitro T{sub 1} seedlings, we showed that anthracene-a three fused benzene ring compound was phytodegraded to naphthalene derivatives, having two benzene rings. {yields} This is the first time that a transgenic plant was shown to have the potential to phytodegrade anthracene. - Abstract: Plants can be used for remediation of polyaromatic hydrocarbons, which are known to be a major concern for human health. Metabolism of xenobiotic compounds in plants occurs in three phases and glutathione transferases (GST) mediate phase II of xenobiotic transformation. Plants, although have GSTs, they are not very efficient for degradation of exogenous recalcitrant xenobiotics including polyaromatic hydrocarbons. Hence, heterologous expression of efficient GSTs in plants may improve their remediation and degradation potential of xenobiotics. In the present study, we investigated the potential of transgenic tobacco plants expressing a Trichoderma virens GST for tolerance, remediation and degradation of anthracene-a recalcitrant polyaromatic hydrocarbon. Transgenic plants with fungal GST showed enhanced tolerance to anthracene compared to control plants. Remediation of {sup 14}C uniformly labeled anthracene from solutions and soil by transgenic tobacco plants was higher compared to wild-type plants. Transgenic plants (T{sub 0} and T{sub 1}) degraded anthracene to naphthalene derivatives, while no such degradation was observed in wild-type plants. The present work has shown that in planta expression of a fungal GST in tobacco imparted enhanced tolerance as well as higher remediation potential of anthracene compared to wild-type plants.

  6. Determination of the serine palmitoyl transferase inhibitor myriocin by electrospray and Q-trap mass spectrometry.

    Science.gov (United States)

    Campisi, Giuseppe Matteo; Signorelli, Paola; Rizzo, Jessica; Ghilardi, Claudio; Antognetti, Jacopo; Caretti, Anna; Lazarević, Jelena S; Strettoi, Enrica; Novelli, Elena; Ghidoni, Riccardo; Rubino, Federico Maria; Paroni, Rita

    2017-12-01

    Myriocin is a potent inhibitor of serine-palmitoyl-transferase, the first and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure myriocin in minute specimens of animal tissue. The chemical analog 14-OH-myriocin was used as the internal standard. The two molecules were extracted from the tissue homogenate by solid-phase extraction, separated by gradient reversed-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole. Detection was accomplished by multiple reaction monitoring, employing the most representative transitions, 400@104 and 402@104 for myriocin and 14-OH-myriocin, respectively. The typical limit of detection and lower limit of quantitation of the optimized method were 0.9 pmol/mL (~0.016 pmol injected) and 2.3 pmol/mL, respectively, and the method was linear up to 250 pmol/mL range (r 2  = 0.9996). The intra- and between-day repeatability afforded a coefficient of variation ≤7.0%. Applications included quantification of myriocin in mouse lungs after 24 h from administration of ~4 nmol by intra-tracheal delivery. Measured levels ranged from 4.11 (median; 2.3-7.4 IQR, n = 4) to 11.7 (median; 7.6-22.7 interquartile range (IQR), n = 6) pmol/lung depending on the different formulations used. Myriocin was also measured in retinas of mice treated by intravitreal injection and ranged from 0.045 (less than the limit of detection) to 0.35 pmol/retina. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Cloning of a glutathione S-transferase decreasing during differentiation of HL60 cell line

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Chul; Park, In Kyu; Lee, Kyu Bo; Sohn, Sang Kyun; Kim, Moo Kyu; Kim, Jung Chul [College of Medicine, Kyungpook National Univ., Taegu (Korea, Republic of)

    1999-06-01

    By sequencing the Expressed Sequence Tags of human dermal papilla cDNA library, we identified a clone named K872 of which the expression decreased during differentiation of HL60 cell line. K872 plasmid DNA was isolated according to QIA plasmid extraction kit (Qiagen GmbH, Germany). The nucleotide sequencing was performed by Sanger's method with K872 plasmid DNA. The most updated GenBank EMBL necleic acid banks were searched through the internet by using BLAST (Basic Local Alignment Search Tools) program. Northern bots were performed using RNA isolated from various human tissues and cancer cell lines. The gene expression of the fusion protein was achieved by His-Patch Thiofusion expression system and the protein product was identified on SDS-PAGE. K872 clone is 1006 nucleotides long, and has a coding region of 675 nucleotides and a 3' non-coding region of 280 nucleotides. The presumed open reading frame starting at the 5' terminus of K872 encodes 226 amino acids, including the initiation methionine residue. The amino acid sequence deduced from the open reading frame of K872 shares 70% identity with that of rat glutathione S-transferase kappa 1 (rGSTK1). The transcripts were expressed inh a variety of human tissues and cancer cells. The levels of transcript were relatively high in those tissues such as heart, skeletal muscle, and peripheral blood leukocyte. It is noteworthy that K872 was found to be abundantly expressed in colorectal cancer and melanoma cell lines. Homology search result suggests that K872 clone is the human homolog of the rGSTK1 which is known to be involved in the resistance of cytotoxic therapy. We propose that meticulous functional analysis should be followed to confirm that.

  8. Constitutive NADPH-dependent electron transferase activity of the Nox4 dehydrogenase domain.

    Science.gov (United States)

    Nisimoto, Yukio; Jackson, Heather M; Ogawa, Hisamitsu; Kawahara, Tsukasa; Lambeth, J David

    2010-03-23

    NADPH oxidase 4 (Nox4) is constitutively active, while Nox2 requires the cytosolic regulatory subunits p47(phox) and p67(phox) and activated Rac with activation by phorbol 12-myristate 13-acetate (PMA). This study was undertaken to identify the domain on Nox4 that confers constitutive activity. Lysates from Nox4-expressing cells exhibited constitutive NADPH- but not NADH-dependent hydrogen peroxide production with a K(m) for NADPH of 55 +/- 10 microM. The concentration of Nox4 in cell lysates was estimated using Western blotting and allowed calculation of a turnover of approximately 200 mol of H(2)O(2) min(-1) (mol of Nox4)(-1). A chimeric protein (Nox2/4) consisting of the Nox2 transmembrane (TM) domain and the Nox4 dehydrogenase (DH) domain showed H(2)O(2) production in the absence of cytosolic regulatory subunits. In contrast, chimera Nox4/2, consisting of the Nox4 TM and Nox2 DH domains, exhibited PMA-dependent activation that required coexpression of regulatory subunits. Nox DH domains from several Nox isoforms were purified and evaluated for their electron transferase activities. Nox1 DH, Nox2 DH, and Nox5 DH domains exhibited barely detectable activities toward artificial electron acceptors, while the Nox4 DH domain exhibited significant rates of reduction of cytochrome c (160 min(-1), largely superoxide dismutase-independent), ferricyanide (470 min(-1)), and other electron acceptors (artificial dyes and cytochrome b(5)). Rates were similar to those observed for H(2)O(2) production by the Nox4 holoenzyme in cell lysates. The activity required added FAD and was seen with NADPH but not NADH. These results indicate that the Nox4 DH domain exists in an intrinsically activated state and that electron transfer from NADPH to FAD is likely to be rate-limiting in the NADPH-dependent reduction of oxygen by holo-Nox4.

  9. Glutathione-S-transferase profiles in the emerald ash borer, Agrilus planipennis.

    Science.gov (United States)

    Rajarapu, Swapna Priya; Mittapalli, Omprakash

    2013-05-01

    The emerald ash borer, Agrilus planipennis Fairmaire is a recently discovered invasive insect pest of ash, Fraxinus spp. in North America. Glutathione-S-transferases (GST) are a multifunctional superfamily of enzymes which function in conjugating toxic compounds to less toxic and excretable forms. In this study, we report the molecular characterization and expression patterns of different classes of GST genes in different tissues and developmental stages plus their specific activity. Multiple sequence alignment of all six A. planipennis GSTs (ApGST-E1, ApGST-E2, ApGST-E3, ApGST-O1, ApGST-S1 and ApGST-μ1) revealed conserved features of insect GSTs and a phylogenetic analysis grouped the GSTs within the epsilon, sigma, omega and microsomal classes of GSTs. Real time quantitative PCR was used to study field collected samples. In larval tissues high mRNA levels for ApGST-E1, ApGST-E3 and ApGST-O1 were obtained in the midgut and Malpighian tubules. On the other hand, ApGST-E2 and ApGST-S1 showed high mRNA levels in fat body and ApGST-μ1 showed constitutive levels in all the tissues assayed. During development, mRNA levels for ApGST-E2 were observed to be the highest in feeding instars, ApGST-S1 in prepupal instars; while the others showed constitutive patterns in all the developmental stages examined. At the enzyme level, total GST activity was similar in all the tissues and developmental stages assayed. Results obtained suggest that A. planipennis is potentially primed with GST-driven detoxification to metabolize ash allelochemicals. To our knowledge this study represents the first report of GSTs in A. planipennis and also in the family of wood boring beetles. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Enhanced tolerance and remediation of anthracene by transgenic tobacco plants expressing a fungal glutathione transferase gene

    International Nuclear Information System (INIS)

    Dixit, Prachy; Mukherjee, Prasun K.; Sherkhane, Pramod D.; Kale, Sharad P.; Eapen, Susan

    2011-01-01

    Highlights: → Transgenic plants expressing a TvGST gene were tested for tolerance, uptake and degradation of anthracene. → Transgenic plants were more tolerant to anthracene and take up more anthracene from soil and solutions compared to control plants. → Using in vitro T 1 seedlings, we showed that anthracene-a three fused benzene ring compound was phytodegraded to naphthalene derivatives, having two benzene rings. → This is the first time that a transgenic plant was shown to have the potential to phytodegrade anthracene. - Abstract: Plants can be used for remediation of polyaromatic hydrocarbons, which are known to be a major concern for human health. Metabolism of xenobiotic compounds in plants occurs in three phases and glutathione transferases (GST) mediate phase II of xenobiotic transformation. Plants, although have GSTs, they are not very efficient for degradation of exogenous recalcitrant xenobiotics including polyaromatic hydrocarbons. Hence, heterologous expression of efficient GSTs in plants may improve their remediation and degradation potential of xenobiotics. In the present study, we investigated the potential of transgenic tobacco plants expressing a Trichoderma virens GST for tolerance, remediation and degradation of anthracene-a recalcitrant polyaromatic hydrocarbon. Transgenic plants with fungal GST showed enhanced tolerance to anthracene compared to control plants. Remediation of 14 C uniformly labeled anthracene from solutions and soil by transgenic tobacco plants was higher compared to wild-type plants. Transgenic plants (T 0 and T 1 ) degraded anthracene to naphthalene derivatives, while no such degradation was observed in wild-type plants. The present work has shown that in planta expression of a fungal GST in tobacco imparted enhanced tolerance as well as higher remediation potential of anthracene compared to wild-type plants.

  11. Genetic polymorphism in three glutathione s-transferase genes and breast cancer risk

    Energy Technology Data Exchange (ETDEWEB)

    Woldegiorgis, S.; Ahmed, R.C.; Zhen, Y.; Erdmann, C.A.; Russell, M.L.; Goth-Goldstein, R.

    2002-04-01

    The role of the glutathione S-transferase (GST) enzyme family is to detoxify environmental toxins and carcinogens and to protect organisms from their adverse effects, including cancer. The genes GSTM1, GSTP1, and GSTT1 code for three GSTs involved in the detoxification of carcinogens, such as polycyclic aromatic hydrocarbons (PAHs) and benzene. In humans, GSTM1 is deleted in about 50% of the population, GSTT1 is absent in about 20%, whereas the GSTP1 gene has a single base polymorphism resulting in an enzyme with reduced activity. Epidemiological studies indicate that GST polymorphisms increase the level of carcinogen-induced DNA damage and several studies have found a correlation of polymorphisms in one of the GST genes and an increased risk for certain cancers. We examined the role of polymorphisms in genes coding for these three GST enzymes in breast cancer. A breast tissue collection consisting of specimens of breast cancer patients and non-cancer controls was analyzed by polymerase chain reaction (PCR) for the presence or absence of the GSTM1 and GSTT1 genes and for GSTP1 single base polymorphism by PCR/RFLP. We found that GSTM1 and GSTT1 deletions occurred more frequently in cases than in controls, and GSTP1 polymorphism was more frequent in controls. The effective detoxifier (putative low-risk) genotype (defined as presence of both GSTM1 and GSTT1 genes and GSTP1 wild type) was less frequent in cases than controls (16% vs. 23%, respectively). The poor detoxifier (putative high-risk) genotype was more frequent in cases than controls. However, the sample size of this study was too small to provide conclusive results.

  12. OGT (O-GlcNAc Transferase) Selectively Modifies Multiple Residues Unique to Lamin A.

    Science.gov (United States)

    Simon, Dan N; Wriston, Amanda; Fan, Qiong; Shabanowitz, Jeffrey; Florwick, Alyssa; Dharmaraj, Tejas; Peterson, Sherket B; Gruenbaum, Yosef; Carlson, Cathrine R; Grønning-Wang, Line M; Hunt, Donald F; Wilson, Katherine L

    2018-05-17

    The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails. Using mass spectrometry, we identified 11 O -GlcNAc sites in a 'sweet spot' unique to lamin A, with up to seven sugars per peptide. Most sites were unpredicted by current algorithms. Double-mutant (S612A/T643A) lamin A tails were still robustly O -GlcNAc-modified at seven sites. By contrast, O -GlcNAcylation was undetectable on tails bearing deletion Δ50, which causes Hutchinson⁻Gilford progeria syndrome, and greatly reduced by deletion Δ35. We conclude that residues deleted in progeria are required for substrate recognition and/or modification by OGT in vitro. Interestingly, deletion Δ35, which does not remove the majority of identified O -GlcNAc sites, does remove potential OGT-association motifs (lamin A residues 622⁻625 and 639⁻645) homologous to that in mouse Tet1. These biochemical results are significant because they identify a novel molecular pathway that may profoundly influence lamin A function. The hypothesis that lamin A is selectively regulated by OGT warrants future testing in vivo, along with two predictions: genetic variants may contribute to disease by perturbing OGT-dependent regulation, and nutrient or other stresses might cause OGT to misregulate wildtype lamin A.

  13. O-GlcNAc transferase regulates transcriptional activity of human Oct4.

    Science.gov (United States)

    Constable, Sandii; Lim, Jae-Min; Vaidyanathan, Krithika; Wells, Lance

    2017-10-01

    O-linked β-N-acetylglucosamine (O-GlcNAc) is a single sugar modification found on many different classes of nuclear and cytoplasmic proteins. Addition of this modification, by the enzyme O-linked N-acetylglucosamine transferase (OGT), is dynamic and inducible. One major class of proteins modified by O-GlcNAc is transcription factors. O-GlcNAc regulates transcription factor properties through a variety of different mechanisms including localization, stability and transcriptional activation. Maintenance of embryonic stem (ES) cell pluripotency requires tight regulation of several key transcription factors, many of which are modified by O-GlcNAc. Octamer-binding protein 4 (Oct4) is one of the key transcription factors required for pluripotency of ES cells and more recently, the generation of induced pluripotent stem (iPS) cells. The action of Oct4 is modulated by the addition of several post-translational modifications, including O-GlcNAc. Previous studies in mice found a single site of O-GlcNAc addition responsible for transcriptional regulation. This study was designed to determine if this mechanism is conserved in humans. We mapped 10 novel sites of O-GlcNAc attachment on human Oct4, and confirmed a role for OGT in transcriptional activation of Oct4 at a site distinct from that found in mouse that allows distinction between different Oct4 target promoters. Additionally, we uncovered a potential new role for OGT that does not include its catalytic function. These results confirm that human Oct4 activity is being regulated by OGT by a mechanism that is distinct from mouse Oct4. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells.

    Science.gov (United States)

    Scharmach, E; Hessel, S; Niemann, B; Lampen, A

    2009-11-30

    The human colon adenocarcinoma cell line Caco-2 is frequently used to study human intestinal metabolism and transport of xenobiotica. Previous studies have shown that both Caco-2 cells and human colon cells constitutively express the multigene family of detoxifying enzymes glutathione S-transferases (GSTs), particularly GST alpha and GST pi. GSTs may play a fundamental role in the molecular interplay between phase I, II enzymes and ABC-transporters. The gut fermentation product, butyrate, can modulate the potential for detoxification. The aim of this study was to investigate the basal expression of further cytosolic GSTs in Caco-2 cells during cell differentiation. In addition, a comparison was made with expression levels in MCF-7 and HepG2, two other cell types with barrier functions. Finally, the butyrate-mediated modulation of gene and protein expression was determined by real time PCR and western blot analysis. In Caco-2, gene and protein expression levels of GST alpha increased during cell differentiation. High levels of GSTO1 and GSTP1 were constantly expressed. No expression of GSTM5 and GSTT1 was detected. HepG2 expressed GSTO1 and MCF-7 GSTZ1 most intensively. No expression of GSTA5, GSTM5, or GSTP1 was detected in either cell. Incubation of Caco-2 cells with butyrate (5 mM) significantly induced GSTA1 and GSTM2 in proliferating Caco-2 cells. In differentiated cells, butyrate tended to increase GSTO1 and GSTP1. The results of this study show that a differentiation-dependent expression of GSTs in Caco-2 cells may reflect the in vivo situation and indicate the potential of butyrate to modify intestinal metabolism. GSTA1-A4 have been identified as good markers for cell differentiation. The Caco-2 cell line is a useful model for assessing the potential of food-related substances to modulate the GST expression pattern.

  15. Primary and secondary structural analyses of glutathione S-transferase pi from human placenta.

    Science.gov (United States)

    Ahmad, H; Wilson, D E; Fritz, R R; Singh, S V; Medh, R D; Nagle, G T; Awasthi, Y C; Kurosky, A

    1990-05-01

    The primary structure of glutathione S-transferase (GST) pi from a single human placenta was determined. The structure was established by chemical characterization of tryptic and cyanogen bromide peptides as well as automated sequence analysis of the intact enzyme. The structural analysis indicated that the protein is comprised of 209 amino acid residues and gave no evidence of post-translational modifications. The amino acid sequence differed from that of the deduced amino acid sequence determined by nucleotide sequence analysis of a cDNA clone (Kano, T., Sakai, M., and Muramatsu, M., 1987, Cancer Res. 47, 5626-5630) at position 104 which contained both valine and isoleucine whereas the deduced sequence from nucleotide sequence analysis identified only isoleucine at this position. These results demonstrated that in the one individual placenta studied at least two GST pi genes are coexpressed, probably as a result of allelomorphism. Computer assisted consensus sequence evaluation identified a hydrophobic region in GST pi (residues 155-181) that was predicted to be either a buried transmembrane helical region or a signal sequence region. The significance of this hydrophobic region was interpreted in relation to the mode of action of the enzyme especially in regard to the potential involvement of a histidine in the active site mechanism. A comparison of the chemical similarity of five known human GST complete enzyme structures, one of pi, one of mu, two of alpha, and one microsomal, gave evidence that all five enzymes have evolved by a divergent evolutionary process after gene duplication, with the microsomal enzyme representing the most divergent form.

  16. Towards understanding oral health.

    Science.gov (United States)

    Zaura, Egija; ten Cate, Jacob M

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term 'oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain microbial community stability in health. However, the oral ecosystem itself is not stable: throughout life an individual undergoes multiple physiological changes while progressing through infancy, childhood, adolescence, adulthood and old age. Recent discussions on the definition of general health have led to the proposal that health is the ability of the individual to adapt to physiological changes, a condition known as allostasis. In this paper the allostasis principle is applied to the oral ecosystem. The multidimensionality of the host factors contributing to allostasis in the oral cavity is illustrated with an example on changes occurring in puberty. The complex phenomenon of oral health and the processes that prevent the ecosystem from collapsing during allostatic changes in the entire body are far from being understood. As yet individual components (e.g. hard tissues, microbiome, saliva, host response) have been investigated, while only by consolidating these and assessing their multidimensional interactions should we be able to obtain a comprehensive understanding of the ecosystem, which in turn could serve to develop rational schemes to maintain health. Adapting such a 'system approach' comes with major practical challenges for the entire research field and will require vast resources and large-scale multidisciplinary collaborations. 2015 S. Karger AG, Basel

  17. Global Oral Health Inequalities

    Science.gov (United States)

    Garcia, I.; Tabak, L.A.

    2011-01-01

    Despite impressive worldwide improvements in oral health, inequalities in oral health status among and within countries remain a daunting public health challenge. Oral health inequalities arise from a complex web of health determinants, including social, behavioral, economic, genetic, environmental, and health system factors. Eliminating these inequalities cannot be accomplished in isolation of oral health from overall health, or without recognizing that oral health is influenced at multiple individual, family, community, and health systems levels. For several reasons, this is an opportune time for global efforts targeted at reducing oral health inequalities. Global health is increasingly viewed not just as a humanitarian obligation, but also as a vehicle for health diplomacy and part of the broader mission to reduce poverty, build stronger economies, and strengthen global security. Despite the global economic recession, there are trends that portend well for support of global health efforts: increased globalization of research and development, growing investment from private philanthropy, an absolute growth of spending in research and innovation, and an enhanced interest in global health among young people. More systematic and far-reaching efforts will be required to address oral health inequalities through the engagement of oral health funders and sponsors of research, with partners from multiple public and private sectors. The oral health community must be “at the table” with other health disciplines and create opportunities for eliminating inequalities through collaborations that can harness both the intellectual and financial resources of multiple sectors and institutions. PMID:21490232

  18. Oral microbiota and cancer

    Directory of Open Access Journals (Sweden)

    Jukka H. Meurman

    2010-08-01

    Full Text Available Inflammation caused by infections may be the most important preventable cause of cancer in general. However, in the oral cavity the role of microbiota in carcinogenesis is not known. Microbial populations on mouth mucosa differ between healthy and malignant sites and certain oral bacterial species have been linked with malignancies but the evidence is still weak in this respect. Nevertheless, oral microorganisms inevitably up-regulate cytokines and other inflammatory mediators that affect the complex metabolic pathways and may thus be involved in carcinogenesis. Poor oral health associates statistically with prevalence of many types of cancer, such as pancreatic and gastrointestinal cancer. Furthermore, several oral micro-organisms are capable of converting alcohol to carcinogenic acetaldehyde which also may partly explain the known association between heavy drinking, smoking, poor oral health and the prevalence of oral and upper gastrointestinal cancer. A different problem is the cancer treatment-caused alterations in oral microbiota which may lead to the emergence of potential pathogens and subsequent other systemic health problems to the patients. Hence clinical guidelines and recommendations have been presented to control oral microbiota in patients with malignant disease, but also in this area the scientific evidence is weak. More controlled studies are needed for further conclusion.

  19. African Journal of Oral Health Sciences

    African Journals Online (AJOL)

    The African Journal of Oral Health Sciences is devoted to research into oral diseases and encourages a multidisciplinary approach. Emphasis is on oral pathology, oral microbiology, oral medicine, oral physiology and biochemistry and related clinical sciences.

  20. Oral candidosis in relation to oral immunity.

    Science.gov (United States)

    Feller, L; Khammissa, R A G; Chandran, R; Altini, M; Lemmer, J

    2014-09-01

    Symptomatic oral infection with Candida albicans is characterized by invasion of the oral epithelium by virulent hyphae that cause tissue damage releasing the inflammatory mediators that initiate and sustain local inflammation. Candida albicans triggers pattern-recognition receptors of keratinocytes, macrophages, monocytes and dendritic cells, stimulating the production of IL-1β, IL-6 and IL-23. These cytokines induce the differentiation of Th17 cells and the generation of IL-17- and/or IL-22-mediated antifungal protective immuno-inflammatory responses in infected mucosa. Some immune cells including NKT cells, γδ T cells and lymphoid cells that are innate to the oral mucosa have the capacity to produce large quantities of IL-17 in response to C. albicans, sufficient to mediate effective protective immunity against C. albicans. On the other hand, molecular structures of commensal C. albicans blastoconidia, although detected by pattern-recognition receptors, are avirulent, do not invade the oral epithelium, do not elicit inflammatory responses in a healthy host, but induce regulatory immune responses that maintain tissue tolerance to the commensal fungi. The type, specificity and sensitivity of the protective immune response towards C. albicans is determined by the outcome of the integrated interactions between the intracellular signalling pathways of specific combinations of activated pattern-recognition receptors (TLR2, TLR4, Dectin-1 and Dectin-2). IL-17-mediated protective immune response is essential for oral mucosal immunity to C. albicans infection. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Sarcoidosis: Oral and extra-oral manifestation

    Directory of Open Access Journals (Sweden)

    Sanjay Gupta

    2015-01-01

    Full Text Available Sarcoidosis is a multisystem granulomatous disease, which is usually associated with the formation of noncaseating granulomas in affected tissues and organs. It is mostly present with bilateral hilar lymphadenopathy, pulmonary infiltration, ocular, and cutaneous lesions. Oral manifestations of this disease are relatively rare. The present case report shows a 40-year-old male with lesions in the soft tissue of oral cavity (buccal mucosa, gingiva, and palate and a diagnosis of sarcoidosis was established following hematological, biochemical and pulmonary function tests, chest radiograph, and histopathological investigation.

  2. Oral cavity and jaw

    International Nuclear Information System (INIS)

    Solntsev, A.M.; Koval', G.Yu.

    1984-01-01

    Radioanatome of oral cavity and jaw is described. Diseases of the teeth, jaw, large salivary glands, temporo-mandibular articulation are considered. Roentgenograms of oral cacity and jaw of healthy people are presented and analyzed as well as roentgenograms in the above-mentioned diseases

  3. Oral Microbiology and Immunology

    DEFF Research Database (Denmark)

    Dahlén, Gunnar; Fiehn, Nils-Erik; Olsen, Ingar

    , dental assistants and trainees may find it a useful source of reference. The contents are based on general microbiology and immunology. Oral microbiology is given particular attention, with examples relevant to oral infectious diseases. Each chapter opens with a relatively short pre-reading section...

  4. Brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Monzen, Yoshio; Ajimu, Akira; Morikawa, Minoru; Hayashi, Nobuyuki; Yoshida, Shintarou; Ashizawa, Kazuto; Hayashi, Kuniaki; Ikenaga, Kouji; Sakamoto, Ichirou.

    1988-01-01

    13 cases with oral cancer were treated using brachytherapy at the Department of Radiology, Nagasaki University Hospital from September 1985 to February 1988. Among 11 cases of tongue cancer, T1 and T2 cases were well controlled by radiation therapy using 226 Ra needles. Cancer of oral floor and buccal mucosa were controlled by the use of 192 Au grains. (author)

  5. Lonafarnib is a potential inhibitor for neovascularization.

    Directory of Open Access Journals (Sweden)

    Linlin Sun

    Full Text Available Atherosclerosis is a common cardiovascular disease that involves the build-up of plaque on the inner walls of the arteries. Intraplaque neovacularization has been shown to be essential in the pathogenesis of atherosclerosis. Previous studies showed that small-molecule compounds targeting farnesyl transferase have the ability to prevent atherosclerosis in apolipoprotein E-deficient mice, but the underlying mechanism remains to be elucidated. In this study, we found that lonafarnib, a specific inhibitor of farnesyl transferase, elicits inhibitory effect on vascular endothelial capillary assembly in vitro in a dose-dependent manner. In addition, we showed that lonafarnib treatment led to a dose-dependent decrease in scratch wound closure in vitro, whereas it had little effect on endothelial cell proliferation. These data indicate that lonafarnib inhibits neovascularization via directly targeting endothelial cells and disturbing their motility. Moreover, we demonstrated that pharmacological inhibition of farnesyl transferase by lonafarnib significantly impaired centrosome reorientation toward the leading edge of endothelial cells. Mechanistically, we found that the catalytic β subunit of farnesyl transferase associated with a cytoskeletal protein important for the establishment and maintenance of cell polarity. Additionally, we showed that lonafarnib remarkably inhibited the expression of the cytoskeletal protein and interrupted its interaction with farnesyl transferase. Our findings thus offer novel mechanistic insight into the protective effect of farnesyl transferase inhibitors on atherosclerosis and provide encouraging evidence for the potential use of this group of agents in inhibiting plaque neovascularization.

  6. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral Surgeries Facial Cosmetic Surgery Facial Injury / Trauma Surgery Obstructive Sleep Apnea (OSA) Oral, Head and Neck Pathology TMJ and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons are ...

  7. American Academy of Oral Medicine

    Science.gov (United States)

    ... Statements Newsletters AAOM: Representing the Discipline of Oral Medicine Oral Medicine is the discipline of dentistry concerned with the ... offers credentialing, resources and professional community for oral medicine practitioners. Our membership provides care to thousands. We ...

  8. What Is an Oral Piercing?

    Science.gov (United States)

    ... to your desktop! more... What Is an Oral Piercing? Article Chapters What Is an Oral Piercing? print full article print this chapter email this article Oral piercing can cause pain, swelling, infection, drooling, taste loss, ...

  9. Literatura Oral Hispanica (Hispanic Oral Literature).

    Science.gov (United States)

    McAlpine, Dave

    As part of a class in Hispanic Oral Literature, students collected pieces of folklore from various Hispanic residents in the region known as "Siouxland" in Iowa. Consisting of some of the folklore recorded from the residents, this paper includes 18 "cuentos y leyendas" (tales and legends), 48 "refranes" (proverbs), 17…

  10. In vivo induction of phase II detoxifying enzymes, glutathione transferase and quinone reductase by citrus triterpenoids

    Directory of Open Access Journals (Sweden)

    Ahmad Hassan

    2010-09-01

    Full Text Available Abstract Background Several cell culture and animal studies demonstrated that citrus bioactive compounds have protective effects against certain types of cancer. Among several classes of citrus bioactive compounds, limonoids were reported to prevent different types of cancer. Furthermore, the structures of citrus limonoids were reported to influence the activity of phase II detoxifying enzymes. The purpose of the study was to evaluate how variations in the structures of citrus limonoids (namely nomilin, deacetyl nomilin, and isoobacunoic acid and a mixture of limonoids would influence phase II enzyme activity in excised tissues from a mouse model. Methods In the current study, defatted sour orange seed powder was extracted with ethyl acetate and subjected to silica gel chromatography. The HPLC, NMR and mass spectra were used to elucidate the purity and structure of compounds. Female A/J mice were treated with three limonoids and a mixture in order to evaluate their effect on phase II enzymes in four different tissues. Assays for glutathione S-transferase and NAD(PH: quinone reductase (QR were used to evaluate induction of phase II enzymatic activity. Results The highest induction of GST against 1-chloro-2,4-dinitrobenzene (CDNB was observed in stomach (whole, 58% by nomilin, followed by 25% isoobacunoic acid and 19% deacetyl nomilin. Deacetyl nomilin in intestine (small as well as liver significantly reduced GST activity against CDNB. Additionally isoobacunoic acid and the limonoid mixture in liver demonstrated a significant reduction of GST activity against CDNB. Nomilin significantly induced GST activity against 4-nitroquinoline 1-oxide (4NQO, intestine (280% and stomach (75% while deacetyl nomilin showed significant induction only in intestine (73%. Induction of GST activity was also observed in intestine (93% and stomach (45% treated with the limonoid mixture. Finally, a significant induction of NAD(PH: quinone reductase (QR activity was

  11. Glutathione S-transferase activity in follicular fluid from women undergoing ovarian stimulation: role in maturation.

    Science.gov (United States)

    Meijide, Susana; Hernández, M Luisa; Navarro, Rosaura; Larreategui, Zaloa; Ferrando, Marcos; Ruiz-Sanz, José Ignacio; Ruiz-Larrea, M Begoña

    2014-10-01

    Female infertility involves an emotional impact for the woman, often leading to a state of anxiety and low self-esteem. The assisted reproduction techniques (ART) are used to overcome the problem of infertility. In a first step of the in vitro fertilization therapy women are subjected to an ovarian stimulation protocol to obtain mature oocytes, which will result in competent oocytes necessary for fertilization to occur. Ovarian stimulation, however, subjects the women to a high physical and psychological stress, thus being essential to improve ART and to find biomarkers of dysfunction and fertility. GSH is an important antioxidant, and is also used in detoxification reactions, catalysed by glutathione S-transferases (GST). In the present work, we have investigated the involvement of GST in follicular maturation. Patients with fertility problems and oocyte donors were recruited for the study. From each woman follicles at two stages of maturation were extracted at the preovulatory stage. Follicular fluid was separated from the oocyte by centrifugation and used as the enzyme source. GST activity was determined based on its conjugation with 3,4-dichloronitrobenzene and the assay was adapted to a 96-well microplate reader. The absorbance was represented against the incubation time and the curves were adjusted to linearity (R(2)>0.990). Results showed that in both donors and patients GST activity was significantly lower in mature oocytes compared to small ones. These results suggest that GST may play a role in the follicle maturation by detoxifying xenobiotics, thus contributing to the normal development of the oocyte. Supported by FIS/FEDER (PI11/02559), Gobierno Vasco (Dep. Educación, Universiades e Investigación, IT687-13), and UPV/EHU (CLUMBER UFI11/20 and PES13/58). The work was approved by the Ethics Committee of the UPV/EHU (CEISH/96/2011/RUIZLARREA), and performed according to the UPV/EHU and IVI-Bilbao agreement (Ref. 2012/01). Copyright © 2014. Published by

  12. Clonorchis sinensis omega-class glutathione transferases are reliable biomarkers for serodiagnosis of clonorchiasis and opisthorchiasis.

    Science.gov (United States)

    Kim, J-G; Ahn, C-S; Sripa, B; Eom, K S; Kang, I; Sohn, W-M; Nawa, Y; Kong, Y

    2018-04-09

    To determine the potential for immunodiagnostic application of two recombinant forms of Clonorchis sinensis omega-class glutathione transferases (rCsGSTo1 and rCsGSTo2) against human small liver-fluke C. sinensis and Opisthorchis viverrini infections. Specific antibody levels against rCsGSTo1 and rCsGSTo2 in patients' sera of egg-positive opisthorchiasis (n = 87) and clonorchiasis (n = 120), as well as those in sera from patients with other helminthic infections (n = 252) and healthy controls (n = 40) were retrospectively analysed by ELISA. We observed highly positive correlation coefficients between specific antibody levels against rCsGSTo1 and rCsGSTo2 and egg counts per gramme of faeces (EPG) of patients with opisthorchiasis (n = 87; r = 0.88 for rCsGSTo1 and r = 0.90 for rCsGSTo2). Sera from opisthorchiasis patients whose EPG counts >100 (n = 43) revealed high antibody titres against both antigens. Patients' sera with low EPG counts (<100, n = 44) also exhibited reliable sensitivities of 93.2% and 97.7% for rCsGSTo1 and rCsGSTo2, respectively. Sera from clonorchiasis patients showed sensitivities of 90% (108/120 samples) and 89.2% (107/120 sera) for rCsGSTo1 and rCsGSTo2. Overall diagnostic sensitivities for liver-fluke infections were 92.3% for rCsGSTo1 (191/207 samples) and 93.2% for rCsGSTo2 (193/207 samples). Specificities were 89.7% (rCsGSTo1) and 97.6% (rCsGSTo2). Detection of specific antibody levels against rCsGSTo1 or rCsGSTo2 might be promising for the serodiagnosis of patients infected with these two phylogenetically close carcinogenic liver-flukes. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  13. SERUM GAMMA-GLUTAMYL TRANSFERASE AS A BIOMARKER OF TYPE-2 DM AMONG CIGARETTE SMOKERS

    Directory of Open Access Journals (Sweden)

    K. Suganthy

    2017-03-01

    Full Text Available BACKGROUND Smoking is one of the most common addictions of modern times and needs to be studied in a community as a public health issue. Also, smoking is a modifiable risk factor for type-2 DM. The smoking-related diseases share common pathophysiologies of imbalance of systemic oxidants and antioxidant status, increased inflammatory reactions, insulin resistance and dyslipidaemia. Biochemical assay of serum Gamma-Glutamyl Transferase (GGT activity is a low cost and highly sensitive laboratory test. Studies have indicated GGT is moderately elevated before the onset of other traditional risk factors for type-2 DM. So, among hepatic markers, the baseline GGT analysis can be an early risk marker of type 2 diabetes in cigarette smokers has to be studied. MATERIALS AND METHODS This is a case-control study on male cigarette smokers. 57 smokers were studied clinically and biochemically for plasma insulin, glucose and liver enzymes including GGT using standard biochemical methods and compared with 42 age and sex matched non-smokers as controls. RESULTS The mean serum GGT in smokers (25.45 ± 10.8 was increased compared to non-smokers (18.8 ± 5.8. Smokers GGT (r=0.396 and HOMA-IR (r=0.352 showed significant positive association with duration of smoking (p24 IU/L. Regression analysis showed none of the diabetic risk factors were observed to be dependent on GGT including other liver enzymes. Regression analysis showed GGT is not an independent risk factor for DM. Although, the mean fasting blood glucose (91.4 ± 21.3, BMI (26.1 ± 9.3 and HOMA-IR (7.3 ± 2.3 was increased among cigarette smokers with GGT >24 IU/L. CONCLUSION The baseline GGT assay in cigarette smokers might be associated with the proinflammatory status or be a marker of oxidative stress of smoke toxins. Smokers with baseline GGT >24 IU/L develop insulin resistance should be investigated in future longitudinal studies for prediabetes to consider cigarette smoking as an important modifiable

  14. Effects of imidacloprid on detoxifying enzyme glutathione S-transferase on Folsomia candida (Collembola).

    Science.gov (United States)

    Sillapawattana, Panwad; Schäffer, Andreas

    2017-04-01

    Chemical analyses of the environment can document contamination by various xenobiotics, but it is also important to understand the effect of pollutants on living organisms. Thus, in the present work, we investigated the effect of the pesticide imidacloprid on the detoxifying enzyme glutathione S-transferase (GST) from Folsomia candida (Collembola), a standard test organism for estimating the effects of pesticides and environmental pollutants on non-target soil arthropods. Test animals were treated with different concentrations of imidacloprid for 48 h. Changes in steady-state levels of GST messenger RNA (mRNA) and GST enzyme activity were investigated. Extracted proteins were separated according to their sizes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the resolved protein bands were detected by silver staining. The size of the glutathione (GSH) pool in Collembola was also determined. A predicted protein sequence of putative GSTs was identified with animals from control group. A 3-fold up-regulation of GST steady-state mRNA levels was detected in the samples treated with 5.0 mg L -1 imidacloprid compared to the control, while a 2.5- and 2.0- fold up-regulation was found in organisms treated with 2.5 and 7.5 mg L -1 imidacloprid, respectively. GST activity increased with increasing imidacloprid amounts from an initial activity of 0.11 μmol min -1  mg -1 protein in the control group up to 0.25 μmol min -1  mg -1 protein in the sample treated with the 5.0 mg L -1 of pesticide. By contrast, the total amount of GSH decreased with increasing imidacloprid concentration. The results suggest that the alteration of GST activity, steady-state level of GST mRNA, and GSH level may be involved in the response of F. candida to the exposure of imidacloprid and can be used as biomarkers to monitor the toxic effects of imidacloprid and other environmental pollutants on Collembola.

  15. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    Energy Technology Data Exchange (ETDEWEB)

    Sakaidani, Yuta [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ichiyanagi, Naoki [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Saito, Chika; Nomura, Tomoko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Ito, Makiko [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Nishio, Yosuke [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Nadano, Daita; Matsuda, Tsukasa [Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan); Furukawa, Koichi [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Okajima, Tetsuya, E-mail: tokajima@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Applied Molecular Biosciences, Nagoya University Graduate School of Bioagricultural Sciences, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer We characterized A130022J15Rik (Eogt1)-a mouse gene homologous to Drosophila Eogt. Black-Right-Pointing-Pointer Eogt1 encodes EGF domain O-GlcNAc transferase. Black-Right-Pointing-Pointer Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. Black-Right-Pointing-Pointer O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-{beta}-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  16. O-linked-N-acetylglucosamine modification of mammalian Notch receptors by an atypical O-GlcNAc transferase Eogt1

    International Nuclear Information System (INIS)

    Sakaidani, Yuta; Ichiyanagi, Naoki; Saito, Chika; Nomura, Tomoko; Ito, Makiko; Nishio, Yosuke; Nadano, Daita; Matsuda, Tsukasa; Furukawa, Koichi; Okajima, Tetsuya

    2012-01-01

    Highlights: ► We characterized A130022J15Rik (Eogt1)—a mouse gene homologous to Drosophila Eogt. ► Eogt1 encodes EGF domain O-GlcNAc transferase. ► Expression of Eogt1 in Drosophila rescued the cell-adhesion defect in the Eogt mutant. ► O-GlcNAcylation reaction in the secretory pathway is conserved through evolution. -- Abstract: O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a unique cytoplasmic and nuclear protein modification that is common in nearly all eukaryotes, including filamentous fungi, plants, and animals. We had recently reported that epidermal growth factor (EGF) repeats of Notch and Dumpy are O-GlcNAcylated by an atypical O-GlcNAc transferase, EOGT, in Drosophila. However, no study has yet shown whether O-GlcNAcylation of extracellular proteins is limited to insects such as Drosophila or whether it occurs in other organisms, including mammals. Here, we report the characterization of A130022J15Rik, a mouse gene homolog of Drosophila Eogt (Eogt 1). Enzymatic analysis revealed that Eogt1 has a substrate specificity similar to that of Drosophila EOGT, wherein the Thr residue located between the fifth and sixth conserved cysteines of the folded EGF-like domains is modified. This observation is supported by the fact that the expression of Eogt1 in Drosophila rescued the cell-adhesion defect caused by Eogt downregulation. In HEK293T cells, Eogt1 expression promoted modification of Notch1 EGF repeats by O-GlcNAc, which was further modified, at least in part, by galactose to generate a novel O-linked-N-acetyllactosamine structure. These results suggest that Eogt1 encodes EGF domain O-GlcNAc transferase and that O-GlcNAcylation reaction in the secretory pathway is a fundamental biochemical process conserved through evolution.

  17. Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

    Science.gov (United States)

    POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

    2015-01-01

    Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

  18. The Fusarium oxysporum gnt2, Encoding a Putative N-Acetylglucosamine Transferase, Is Involved in Cell Wall Architecture and Virulence

    Science.gov (United States)

    López-Fernández, Loida; Ruiz-Roldán, Carmen; Pareja-Jaime, Yolanda; Prieto, Alicia; Khraiwesh, Husam; Roncero, M. Isabel G.

    2013-01-01

    With the aim to decipher the molecular dialogue and cross talk between Fusarium oxysporum f.sp. lycopersci and its host during infection and to understand the molecular bases that govern fungal pathogenicity, we analysed genes presumably encoding N-acetylglucosaminyl transferases, involved in glycosylation of glycoproteins, glycolipids, proteoglycans or small molecule acceptors in other microorganisms. In silico analysis revealed the existence of seven putative N-glycosyl transferase encoding genes (named gnt) in F. oxysporum f.sp. lycopersici genome. gnt2 deletion mutants showed a dramatic reduction in virulence on both plant and animal hosts. Δgnt2 mutants had αalterations in cell wall properties related to terminal αor β-linked N-acetyl glucosamine. Mutant conidia and germlings also showed differences in structure and physicochemical surface properties. Conidial and hyphal aggregation differed between the mutant and wild type strains, in a pH independent manner. Transmission electron micrographs of germlings showed strong cell-to-cell adherence and the presence of an extracellular chemical matrix. Δgnt2 cell walls presented a significant reduction in N-linked oligosaccharides, suggesting the involvement of Gnt2 in N-glycosylation of cell wall proteins. Gnt2 was localized in Golgi-like sub-cellular compartments as determined by fluorescence microscopy of GFP::Gnt2 fusion protein after treatment with the antibiotic brefeldin A or by staining with fluorescent sphingolipid BODIPY-TR ceramide. Furthermore, density gradient ultracentrifugation allowed co-localization of GFP::Gnt2 fusion protein and Vps10p in subcellular fractions enriched in Golgi specific enzymatic activities. Our results suggest that N-acetylglucosaminyl transferases are key components for cell wall structure and influence interactions of F. oxysporum with both plant and animal hosts during pathogenicity. PMID:24416097

  19. The Fusarium oxysporum gnt2, encoding a putative N-acetylglucosamine transferase, is involved in cell wall architecture and virulence.

    Directory of Open Access Journals (Sweden)

    Loida López-Fernández

    Full Text Available With the aim to decipher the molecular dialogue and cross talk between Fusarium oxysporum f.sp. lycopersci and its host during infection and to understand the molecular bases that govern fungal pathogenicity, we analysed genes presumably encoding N-acetylglucosaminyl transferases, involved in glycosylation of glycoproteins, glycolipids, proteoglycans or small molecule acceptors in other microorganisms. In silico analysis revealed the existence of seven putative N-glycosyl transferase encoding genes (named gnt in F. oxysporum f.sp. lycopersici genome. gnt2 deletion mutants showed a dramatic reduction in virulence on both plant and animal hosts. Δgnt2 mutants had αalterations in cell wall properties related to terminal αor β-linked N-acetyl glucosamine. Mutant conidia and germlings also showed differences in structure and physicochemical surface properties. Conidial and hyphal aggregation differed between the mutant and wild type strains, in a pH independent manner. Transmission electron micrographs of germlings showed strong cell-to-cell adherence and the presence of an extracellular chemical matrix. Δgnt2 cell walls presented a significant reduction in N-linked oligosaccharides, suggesting the involvement of Gnt2 in N-glycosylation of cell wall proteins. Gnt2 was localized in Golgi-like sub-cellular compartments as determined by fluorescence microscopy of GFP::Gnt2 fusion protein after treatment with the antibiotic brefeldin A or by staining with fluorescent sphingolipid BODIPY-TR ceramide. Furthermore, density gradient ultracentrifugation allowed co-localization of GFP::Gnt2 fusion protein and Vps10p in subcellular fractions enriched in Golgi specific enzymatic activities. Our results suggest that N-acetylglucosaminyl transferases are key components for cell wall structure and influence interactions of F. oxysporum with both plant and animal hosts during pathogenicity.

  20. Alterations at the peptidyl transferase centre of the ribosome induced by the synergistic action of the streptogramins dalfopristin and quinupristin

    Directory of Open Access Journals (Sweden)

    Fucini Paola

    2004-04-01

    Full Text Available Abstract Background The bacterial ribosome is a primary target of several classes of antibiotics. Investigation of the structure of the ribosomal subunits in complex with different antibiotics can reveal the mode of inhibition of ribosomal protein synthesis. Analysis of the interactions between antibiotics and the ribosome permits investigation of the specific effect of modifications leading to antimicrobial resistances. Streptogramins are unique among the ribosome-targeting antibiotics because they consist of two components, streptogramins A and B, which act synergistically. Each compound alone exhibits a weak bacteriostatic activity, whereas the combination can act bactericidal. The streptogramins A display a prolonged activity that even persists after removal of the drug. However, the mode of activity of the streptogramins has not yet been fully elucidated, despite a plethora of biochemical and structural data. Results The investigation of the crystal structure of the 50S ribosomal subunit from Deinococcus radiodurans in complex with the clinically relevant streptogramins quinupristin and dalfopristin reveals their unique inhibitory mechanism. Quinupristin, a streptogramin B compound, binds in the ribosomal exit tunnel in a similar manner and position as the macrolides, suggesting a similar inhibitory mechanism, namely blockage of the ribosomal tunnel. Dalfopristin, the corresponding streptogramin A compound, binds close to quinupristin directly within the peptidyl transferase centre affecting both A- and P-site occupation by tRNA molecules. Conclusions The crystal structure indicates that the synergistic effect derives from direct interaction between both compounds and shared contacts with a single nucleotide, A2062. Upon binding of the streptogramins, the peptidyl transferase centre undergoes a significant conformational transition, which leads to a stable, non-productive orientation of the universally conserved U2585. Mutations of this r

  1. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral and maxillofacial surgeons surgically treat the soft tissues of the face, mouth ... involving skin, muscle, bone and cartilage finely attune the oral and maxillofacial ...

  2. Examining the association between oral health and oral HPV infection.

    Science.gov (United States)

    Bui, Thanh Cong; Markham, Christine M; Ross, Michael Wallis; Mullen, Patricia Dolan

    2013-09-01

    Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25-1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.

  3. Expression of an enzymatically active Yb3 glutathione S-transferase in Escherichia coli and identification of its natural form in rat brain.

    Science.gov (United States)

    Abramovitz, M; Ishigaki, S; Felix, A M; Listowsky, I

    1988-11-25

    Glutathione S-transferases containing Yb3 subunits are relatively uncommon forms that are expressed in a tissue-specific manner and have not been identified unequivocally or characterized. A cDNA clone containing the entire coding sequence of Yb3 glutathione S-transferase mRNA was incorporated into a pIN-III expression vector used to transform Escherichia coli. A fusion Yb3-protein containing 14 additional amino acid residues at its N terminus was purified to homogeneity. Recombinant Yb3 was enzymatically active with both 1-chloro-2,4-dinitrobenzene and 1,2-dichloro-4-nitrobenzene as substrates but lacked glutathione peroxidase activity. Substrate specificity patterns of recombinant Yb3 were more limited than those of glutathione S-transferase isoenzymes containing Yb1- or Yb2-type subunits. Peptides corresponding to unique amino acid sequences of Yb3 as well as a peptide from a region of homology with Yb1 and Yb2 subunits were synthesized. These synthetic peptides were used to raise antibodies specific to Yb3 and others that cross-reacted with all Yb forms. Immunoblotting was utilized to identify the natural counterpart of recombinant Yb3 among rat glutathione transferases. Brain and testis glutathione S-transferases were rich in Yb3 subunits, but very little was found in liver or kidney. Physical properties, substrate specificities, and binding patterns of the recombinant protein paralleled properties of the natural isoenzyme isolated from brain.

  4. Prevention of gingival trauma : Oral hygiene devices and oral piercings

    NARCIS (Netherlands)

    Hoenderdos, N.L.

    2017-01-01

    Maintaining healthy teeth and soft oral tissues for life is important. Oral hygiene devices and oral piercings can damage the soft oral tissues. This thesis investigates the safety of manual toothbrushes, interdental brushes and rubber bristles interdental cleaners by analysing the gingival abrasion

  5. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

  6. Cromolyn Oral Inhalation

    Science.gov (United States)

    ... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

  7. Intravenous versus oral etoposide

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

    2018-01-01

    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

  8. Fostering oral presentation performance

    NARCIS (Netherlands)

    Ginkel, van Stan; Gulikers, Judith; Biemans, Harm; Mulder, Martin

    2017-01-01

    Previous research revealed significant differences in the effectiveness of various feedback sources for encouraging students’ oral presentation performance. While former studies emphasised the superiority of teacher feedback, it remains unclear whether the quality of feedback actually differs

  9. Oral Cancer Foundation

    Science.gov (United States)

    ... Get involved Understanding Dental Research People Resources About Understanding Events Get involved Dental Research Resources Contact Sitemap The Oral Cancer Foundation admin 2017-11-12T16:49:25+ ...

  10. Crystallization and preliminary X-ray diffraction analysis of a glutathione S-transferase from Xylella fastidiosa

    International Nuclear Information System (INIS)

    Garcia, Wanius; Travensolo, Regiane F.; Rodrigues, Nathalia C.; Muniz, João R. C.; Caruso, Célia S.; Lemos, Eliana G. M.; Araujo, Ana Paula U.; Carrilho, Emanuel

    2008-01-01

    Glutathione S-transferase from X. fastidiosa (xfGST) has been overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 2.23 Å. Glutathione S-transferases (GSTs) form a group of multifunctional isoenzymes that catalyze the glutathione-dependent conjugation and reduction reactions involved in the cellular detoxification of xenobiotic and endobiotic compounds. GST from Xylella fastidiosa (xfGST) was overexpressed in Escherichia coli and purified by conventional affinity chromatography. In this study, the crystallization and preliminary X-ray analysis of xfGST is described. The purified protein was crystallized by the vapour-diffusion method, producing crystals that belonged to the triclinic space group P1. The unit-cell parameters were a = 47.73, b = 87.73, c = 90.74 Å, α = 63.45, β = 80.66, γ = 94.55°. xfGST crystals diffracted to 2.23 Å resolution on a rotating-anode X-ray source

  11. Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

    International Nuclear Information System (INIS)

    LaCourse, E. James; Hernandez-Viadel, Mariluz; Jefferies, James R.; Svendsen, Claus; Spurgeon, David J.; Barrett, John; John Morgan, A.; Kille, Peter; Brophy, Peter M.

    2009-01-01

    The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

  12. Glutathione transferase (GST) as a candidate molecular-based biomarker for soil toxin exposure in the earthworm Lumbricus rubellus

    Energy Technology Data Exchange (ETDEWEB)

    LaCourse, E. James, E-mail: james.la-course@liverpool.ac.u [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Hernandez-Viadel, Mariluz; Jefferies, James R. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); Svendsen, Claus; Spurgeon, David J. [Centre for Ecology and Hydrology, Huntingdon PE28 2LS (United Kingdom); Barrett, John [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom); John Morgan, A.; Kille, Peter [Biosciences, University of Cardiff, Cardiff CF10 3TL (United Kingdom); Brophy, Peter M. [Institute of Biological, Environmental, and Rural Sciences, Aberystwyth University, Aberystwyth SY23 3DA (United Kingdom)

    2009-08-15

    The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. - This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

  13. The role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations.

    LENUS (Irish Health Repository)

    Flanagan, J M

    2010-02-01

    Classical or transferase-deficient galactosaemia is an inherited metabolic disorder caused by mutation in the human Galactose-1-phosphate uridyl transferase (GALT) gene. Of some 170 causative mutations reported, fewer than 10% are observed in more than one geographic region or ethnic group. To better understand the population history of the common GALT mutations, we have established a haplotyping system for the GALT locus incorporating eight single nucleotide polymorphisms and three short tandem repeat markers. We analysed haplotypes associated with the three most frequent GALT gene mutations, Q188R, K285N and Duarte-2 (D2), and estimated their age. Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations. The Q188R mutation arose in central Europe within the last 20 000 years, with its observed east-west cline of increasing relative allele frequency possibly being due to population expansion during the re-colonization of Europe by Homo sapiens in the Mesolithic age. K285N was found to be a younger mutation that originated in Eastern Europe and is probably more geographically restricted as it arose after all major European population expansions. The D2 variant was found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

  14. Acute cadmium intoxication induces alpha-class glutathione S-transferase protein synthesis and enzyme activity in rat liver

    International Nuclear Information System (INIS)

    Casalino, Elisabetta; Sblano, Cesare; Calzaretti, Giovanna; Landriscina, Clemente

    2006-01-01

    Acute cadmium intoxication affects glutathione S-transferase (GST) in rat liver. It has been found that 24 h after i.p. cadmium administration to rats, at a dose of 2.5 mg CdCl 2 kg -1 body weight, the activity of this enzyme in liver cytosol increased by 40%. A less stimulatory effect persisted till 48 h and thereafter the enzyme activity normalized. Since, GST isoenzymes belong to different classes in mammalian tissues, we used quantitative immunoassays to verify which family of GST isoenzymes is influenced by this intoxication. Only alpha-class glutathione S-transferase (α-GST) proteins were detected in rat liver cytosol and their level increased by about 25%, 24 h after cadmium treatment. No pi-GST isoforms were found in liver cytosol from either normal or cadmium-treated rats. Co-administration of actinomycin D with cadmium normalized both the protein level and the activity of α-GST, suggesting that some effect occurs on enzyme transcription of these isoenzymes by this metal. On the other hand, it seems unlikely that the stimulatory effect is due to the high level of peroxides caused by lipid peroxidation, since Vitamin E administration strongly reduced the TBARS level, but did not cause any GST activity decrease

  15. Crystallization and preliminary X-ray diffraction analysis of a glutathione S-transferase from Xylella fastidiosa

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Wanius, E-mail: wanius@if.sc.usp.br [Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Travensolo, Regiane F. [Grupo de Bioanalítica, Microfabricação e Separações, Instituto de Química de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Rodrigues, Nathalia C.; Muniz, João R. C. [Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Caruso, Célia S. [Grupo de Bioanalítica, Microfabricação e Separações, Instituto de Química de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Lemos, Eliana G. M. [Laboratório de Bioquímica de Microrganismos e de Plantas, Departamento de Tecnologia, UNESP, Jaboticabal (Brazil); Araujo, Ana Paula U. [Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Carrilho, Emanuel, E-mail: wanius@if.sc.usp.br [Grupo de Bioanalítica, Microfabricação e Separações, Instituto de Química de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil); Laboratório de Biofísica Molecular ‘Sérgio Mascarenhas’, Instituto de Física de São Carlos, Universidade de São Paulo (USP), São Carlos (Brazil)

    2008-02-01

    Glutathione S-transferase from X. fastidiosa (xfGST) has been overexpressed in E. coli, purified and crystallized. Diffraction data were collected to 2.23 Å. Glutathione S-transferases (GSTs) form a group of multifunctional isoenzymes that catalyze the glutathione-dependent conjugation and reduction reactions involved in the cellular detoxification of xenobiotic and endobiotic compounds. GST from Xylella fastidiosa (xfGST) was overexpressed in Escherichia coli and purified by conventional affinity chromatography. In this study, the crystallization and preliminary X-ray analysis of xfGST is described. The purified protein was crystallized by the vapour-diffusion method, producing crystals that belonged to the triclinic space group P1. The unit-cell parameters were a = 47.73, b = 87.73, c = 90.74 Å, α = 63.45, β = 80.66, γ = 94.55°. xfGST crystals diffracted to 2.23 Å resolution on a rotating-anode X-ray source.

  16. Activity-Based Probes for Isoenzyme- and Site-Specific Functional Characterization of Glutathione S -Transferases

    Energy Technology Data Exchange (ETDEWEB)

    Stoddard, Ethan G. [Chemical Biology and Exposure; Killinger, Bryan J. [Chemical Biology and Exposure; Nair, Reji N. [Chemical Biology and Exposure; Sadler, Natalie C. [Chemical Biology and Exposure; Volk, Regan F. [Chemical Biology and Exposure; Purvine, Samuel O. [Chemical Biology and Exposure; Shukla, Anil K. [Chemical Biology and Exposure; Smith, Jordan N. [Chemical Biology and Exposure; Wright, Aaron T. [Chemical Biology and Exposure

    2017-11-01

    Glutathione S-transferases (GSTs) comprise a highly diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione to various endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured by colorimetric assays, measurement of the individual contribution from specific isoforms and their contribution to the detoxification of xenobiotics in complex biological samples has not been possible. For this reason, we have developed two activity-based probes that characterize active glutathione transferases in mammalian tissues. The GST active site is comprised of a glutathione binding “G site” and a distinct substrate binding “H site”. Therefore, we developed (1) a glutathione-based photoaffinity probe (GSH-ABP) to target the “G site”, and (2) a probe designed to mimic a substrate molecule and show “H site” activity (GST-ABP). The GSH-ABP features a photoreactive moiety for UV-induced covalent binding to GSTs and glutathione-binding enzymes. The GST-ABP is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competitors in liver homogenates. Herein, we present robust tools for the novel characterization of enzyme- and active site-specific GST activity in mammalian model systems.

  17. Cantharidin Impedes Activity of Glutathione S-Transferase in the Midgut of Helicoverpa armigera Hübner

    Directory of Open Access Journals (Sweden)

    Ya Lin Zhang

    2013-03-01

    Full Text Available Previous investigations have implicated glutathione S-transferases (GSTs as one of the major reasons for insecticide resistance. Therefore, effectiveness of new candidate compounds depends on their ability to inhibit GSTs to prevent metabolic detoxification by insects. Cantharidin, a terpenoid compound of insect origin, has been developed as a bio-pesticide in China, and proves highly toxic to a wide range of insects, especially lepidopteran. In the present study, we test cantharidin as a model compound for its toxicity, effects on the mRNA transcription of a model Helicoverpa armigera glutathione S-transferase gene (HaGST and also for its putative inhibitory effect on the catalytic activity of GSTs, both in vivo and in vitro in Helicoverpa armigera, employing molecular and biochemical methods. Bioassay results showed that cantharidin was highly toxic to H. armigera. Real-time qPCR showed down-regulation of the HaGST at the mRNA transcript ranging from 2.5 to 12.5 folds while biochemical assays showed in vivo inhibition of GSTs in midgut and in vitro inhibition of rHaGST. Binding of cantharidin to HaGST was rationalized by homology and molecular docking simulations using a model GST (1PN9 as a template structure. Molecular docking simulations also confirmed accurate docking of the cantharidin molecule to the active site of HaGST impeding its catalytic activity.

  18. Maintaining women's oral health.

    Science.gov (United States)

    McCann, A L; Bonci, L

    2001-07-01

    Women must adopt health-promoting strategies for both general health and the oral cavity, because the health of a woman's body and oral cavity are bidirectional. For general health-maintenance strategies, dental practitioners should actively advise women to minimize alcohol use, abstain from or cease smoking, stay physically active, and choose the right foods to nourish both the body and mind. For oral health-maintenance strategies, dental practitioners should advise women on how to prevent or control oral infections, particularly dental caries and periodontal diseases. Specifically, women need to know how to remove plaque from the teeth mechanically, use appropriate chemotherapeutic agents and dentifrices, use oral irrigation, and control halitosis. Dental practitioners also need to stress the importance of regular maintenance visits for disease prevention. Adolescent women are more prone to gingivitis and aphthous ulcers when they begin their menstrual cycles and need advice about cessation of tobacco use, mouth protection during athletic activities, cleaning orthodontic appliances, developing good dietary habits, and avoiding eating disorders. Women in early to middle adulthood may be pregnant or using oral contraceptives with concomitant changes in oral tissues. Dental practitioners need to advise them how to take care of the oral cavity during these changes and how to promote the health of their infants, including good nutrition. Older women experience the onset of menopause and increased vulnerability to osteoporosis. They may also experience xerostomia and burning mouth syndrome. Dental practitioners need to help women alleviate these symptoms and encourage them to continue good infection control and diet practices.

  19. ON ORAL CANCER

    Directory of Open Access Journals (Sweden)

    P. V. Svetitsky

    2012-01-01

    Full Text Available The paper analyzes a rise in the incidence of oral cancer in the Rostov Region since the 1990s. The study has indicated that this rise is associated with regional population growth due to the forced migrants after the collapse of the USSR. Financial problems, unbalanced nutrition, poor oral hygiene, and depression in this group of patients have contributed to the higher incidence of precancers and cancers.

  20. Oral vs. salivary diagnostics

    Science.gov (United States)

    Marques, Joana; Corby, Patricia M.; Barber, Cheryl A.; Abrams, William R.; Malamud, Daniel

    2015-05-01

    The field of "salivary diagnostics" includes studies utilizing samples obtained from a variety of sources within the oral cavity. These samples include; whole unstimulated saliva, stimulated whole saliva, duct saliva collected directly from the parotid, submandibular/sublingual glands or minor salivary glands, swabs of the buccal mucosa, tongue or tonsils, and gingival crevicular fluid. Many publications state "we collected saliva from subjects" without fully describing the process or source of the oral fluid. Factors that need to be documented in any study include the time of day of the collection, the method used to stimulate and collect the fluid, and how much fluid is being collected and for how long. The handling of the oral fluid during and post-collection is also critical and may include addition of protease or nuclease inhibitors, centrifugation, and cold or frozen storage prior to assay. In an effort to create a standard protocol for determining a biomarker's origin we carried out a pilot study collecting oral fluid from 5 different sites in the mouth and monitoring the concentrations of pro- and anti-inflammatory cytokines detected using MesoScaleDiscovery (MSD) electrochemiluminesence assays. Our data suggested that 3 of the cytokines are primarily derived from the submandibular gland, while 7 of the cytokines come from a source other than the major salivary glands such as the minor salivary glands or cells in the oral mucosae. Here we review the literature on monitoring biomarkers in oral samples and stress the need for determining the blood/saliva ratio when a quantitative determination is needed and suggest that the term oral diagnostic be used if the source of an analyte in the oral cavity is unknown.

  1. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  2. Glutathione S transferase polymorphisms influence on iron overload in β-thalassemia patients

    Directory of Open Access Journals (Sweden)

    Serena Sclafani

    2013-11-01

    Full Text Available In patients with β-thalassemia iron overload that leads to damage to vital organs is observed. Glutathione S transferase (GST enzymes have an antioxidant role in detoxification processes of toxic substances. This role is determined genetically. In this study, we correlated GSTT1 and GSTM1 genotypes with iron overload measured with direct and indirect non-invasive methods; in particular, we used serum ferritin and signal intensity of the magnetic resonance image (MRI in 42 patients with β-thalassemia, which were regularly subjected to chelation and transfusion therapy. Multiplex polymerase chain reaction was used to determine the genotype. The loss of both alleles leads to a decreased value of liver and heart MRI-signal intensity with a consequent iron accumulation in these organs; the loss of only one allele doesn’t lead to relevant overload. Serum ferritin doesn’t appear to be correlated to iron overload instead. 对于β-地中海贫血患者,由于铁过量而造成重要器官受损的情况也在观察之中。谷胱甘肽S转移酶(GST 酶类在对有毒物质进行解毒的过程中有着抗氧化剂的作用。该作用是由基因决定的。 在这份研究中,我们运用了直接和间接非侵入性的方法对基因型铁过量GSTT1 和GSTM1进行了相关性测量;特别地,我们对42位定期接受螯合和输血治疗的β-地中海贫血患者进行了血清铁蛋白和磁共振强度图像(MRI 的测试。 多重聚合酶链反应的测试也被运用来确定该基因型。 该两种等位基因的缺失,导致了肝功能减损及心脏磁共振强度的下降,并造成了在这些器官中铁含量的积累;其中一种等位基因的缺失并不会导致过度的铁含量。血清蛋白和铁过量之间,看起来并不存在相关性。

  3. Determinants of Oral Health: Does Oral Health Literacy Matter?

    OpenAIRE

    Naghibi Sistani, Mohammad Mehdi; Yazdani, Reza; Virtanen, Jorma; Pakdaman, Afsaneh; Murtomaa, Heikki

    2013-01-01

    Objective. To evaluate oral health literacy, independent of other oral health determinants, as a risk indicator for self-reported oral health. Methods. A cross-sectional population-based survey conducted in Tehran, Iran. Multiple logistic regression analysis served to estimate the predictive effect of oral health literacy on self-reported oral health status (good versus poor) controlling for socioeconomic and demographic factors and tooth-brushing behavior. Results. In all, among 1031 partici...

  4. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    OpenAIRE

    Tanaka, Takuji; Tanaka, Mayu; Tanaka, Takahiro

    2011-01-01

    Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important adv...

  5. Oral microbiome and oral and gastrointestinal cancer risk

    OpenAIRE

    Ahn, Jiyoung; Chen, Calvin Y.; Hayes, Richard B.

    2012-01-01

    A growing body of evidence implicates human oral bacteria in the etiology of oral and gastrointestinal cancers. Epidemiological studies consistently report increased risks of these cancers in men and women with periodontal disease or tooth loss, conditions caused by oral bacteria. More than 700 bacterial species inhabit the oral cavity, including at least 11 bacterial phyla and 70 genera. Oral bacteria may activate alcohol and smoking-related carcinogens locally or act systemically, through c...

  6. Ethnicity and oral cancer.

    Science.gov (United States)

    Scully, C; Bedi, R

    2000-09-01

    Oral squamous-cell carcinoma, the main type of oral cancer, is among the ten most common cancers in the world. The aims of this paper were first, to consider whether there was evidence of marked ethnic variations in the incidence, management, and survival of oral cancer, and then, to review possible explanations for these variations. Evidence from the literature suggests that there is marked, inter-country variation in both the incidence and mortality from oral cancer. There is also growing evidence of intracountry ethnic differences, mostly reported in the UK and USA. These variations among ethnic groups have been attributed mainly to specific risk factors, such as alcohol and tobacco (smoking and smokeless), but dietary factors and the existence of genetic predispositions may also play a part. Variations in access to care services are also an apparent factor. The extent of ethnic differences in oral cancer is masked by the scarcity of information available. Where such data are accessible, there are clear disparities in both incidence and mortality of oral cancer between ethnic groups.

  7. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ...

  8. Head, Neck, and Oral Cancer

    Science.gov (United States)

    ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ... find out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ...

  9. Strengthening of oral health systems

    DEFF Research Database (Denmark)

    Petersen, Poul Erik

    2014-01-01

    is either due to low availability and accessibility of oral health care or because oral health care is costly. In all countries, the poor and disadvantaged population groups are heavily affected by a high burden of oral disease compared to well-off people. Promotion of oral health and prevention of oral...... diseases must be provided through financially fair primary health care and public health intervention. Integrated approaches are the most cost-effective and realistic way to close the gap in oral health between rich and poor. The World Health Organization (WHO) Oral Health Programme will work......Around the globe many people are suffering from oral pain and other problems of the mouth or teeth. This public health problem is growing rapidly in developing countries where oral health services are limited. Significant proportions of people are underserved; insufficient oral health care...

  10. ORAL MYIASIS CONVERTING TO ORAL SQUAMOUS CELL CARCINOMA

    Directory of Open Access Journals (Sweden)

    Akshay

    2015-10-01

    Full Text Available INTRODUCTION: Oral Myiasis, a condition of infestation of the body by fly larvae (maggots is a rare pathology in humans. It is associated with poor oral hygiene, alcoholism, senility, suppurating lesions, severe halitosis. It is seen frequently in tropical countries and hot climatic regions. The reported cases in literature of oral Myiasis associated with oral cancer are few. The treatment is a mechanical removal of the maggots but a systemic treatment with Ivermectin, a semi - synthetic macrolide antibiotic, has been used successfully for treatment for oral m yiasis. We present a case of 55 yr old male alcoholic patient with oral myiasis with extensive proliferative growth of oral cavity. Our patient was managed with manual debridement and administration of systemic ivermect in along with antibiotic coverage. Incisional biopsy of the proliferative lesion showed well differentiated squamous cell carcinoma. Thus our patient showed presence of oral myiasis in association with oral squamous cell carcinoma.

  11. Communication among Oral Bacteria

    Science.gov (United States)

    Kolenbrander, Paul E.; Andersen, Roxanna N.; Blehert, David S.; Egland, Paul G.; Foster, Jamie S.; Palmer, Robert J.

    2002-01-01

    Human oral bacteria interact with their environment by attaching to surfaces and establishing mixed-species communities. As each bacterial cell attaches, it forms a new surface to which other cells can adhere. Adherence and community development are spatiotemporal; such order requires communication. The discovery of soluble signals, such as autoinducer-2, that may be exchanged within multispecies communities to convey information between organisms has emerged as a new research direction. Direct-contact signals, such as adhesins and receptors, that elicit changes in gene expression after cell-cell contact and biofilm growth are also an active research area. Considering that the majority of oral bacteria are organized in dense three-dimensional biofilms on teeth, confocal microscopy and fluorescently labeled probes provide valuable approaches for investigating the architecture of these organized communities in situ. Oral biofilms are readily accessible to microbiologists and are excellent model systems for studies of microbial communication. One attractive model system is a saliva-coated flowcell with oral bacterial biofilms growing on saliva as the sole nutrient source; an intergeneric mutualism is discussed. Several oral bacterial species are amenable to genetic manipulation for molecular characterization of communication both among bacteria and between bacteria and the host. A successful search for genes critical for mixed-species community organization will be accomplished only when it is conducted with mixed-species communities. PMID:12209001

  12. [Oral health in pregnancy].

    Science.gov (United States)

    Blagojević, Duska; Brkanić, Tatjana; Stojić, Sinisa

    2002-01-01

    Good oral health care during pregnancy is essential but often overlooked factor of dental growth as well as of other structures of oral cavity. Pregnancy is the time when conscious approach to preventive oral care should increase. Preventive measures during pregnancy mean usage of fluorides, special dietary measures and increased oral hygiene habits. Preventive measures in pregnant women have one goal: providing conditions for development of fetal teeth as well as preventing tooth decay in pregnant women. The optimal period for introducing preventive measures is the first trimester of pregnancy. Because of hormonal alterations there is an increased incidence of dental diseases: gingivitis and low salivary pH (inflammation and bleeding gums). Eating habits of pregnant women may lead to frequent snacking on candy or other decay-promoting foods, thereby increasing the risk of caries. However, very poor oral health, possible dental complications and their consequences to the health as well as emotional status represent very strong reasons for activation of dental health care in this period.

  13. The Oral Microbiota.

    Science.gov (United States)

    Arweiler, Nicole B; Netuschil, Lutz

    2016-01-01

    The oral microbiota represents an important part of the human microbiota, and includes several hundred to several thousand diverse species. It is a normal part of the oral cavity and has an important function to protect against colonization of extrinsic bacteria which could affect systemic health. On the other hand, the most common oral diseases caries, gingivitis and periodontitis are based on microorganisms. While (medical) research focused on the planktonic phase of bacteria over the last 100 years, it is nowadays generally known, that oral microorganisms are organised as biofilms. On any non-shedding surfaces of the oral cavity dental plaque starts to form, which meets all criteria for a microbial biofilm and is subject to the so-called succession. When the sensitive ecosystem turns out of balance - either by overload or weak immune system - it becomes a challenge for local or systemic health. Therefore, the most common strategy and the golden standard for the prevention of caries, gingivitis and periodontitis is the mechanical removal of this biofilms from teeth, restorations or dental prosthesis by regular toothbrushing.

  14. Oral health during pregnancy.

    Science.gov (United States)

    Silk, Hugh; Douglass, Alan B; Douglass, Joanna M; Silk, Laura

    2008-04-15

    Oral health care in pregnancy is often avoided and misunderstood by physicians, dentists, and patients. Evidence-based practice guidelines are still being developed. Research suggests that some prenatal oral conditions may have adverse consequences for the child. Periodontitis is associated with preterm birth and low birth weight, and high levels of cariogenic bacteria in mothers can lead to increased dental caries in the infant. Other oral lesions, such as gingivitis and pregnancy tumors, are benign and require only reassurance and monitoring. Every pregnant woman should be screened for oral risks, counseled on proper oral hygiene, and referred for dental treatment when necessary. Dental procedures such as diagnostic radiography, periodontal treatment, restorations, and extractions are safe and are best performed during the second trimester. Xylitol and chlorhexidine may be used as adjuvant therapy for high-risk mothers in the early postpartum period to reduce transmission of cariogenic bacteria to their infants. Appropriate dental care and prevention during pregnancy may reduce poor prenatal outcomes and decrease infant caries.

  15. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  16. Degenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions

    International Nuclear Information System (INIS)

    Baldi, D.; Izzotti, A.; Bonica, P.; Pera, P.; Pulliero, A.

    2009-01-01

    Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.

  17. Degenerative periodontal-diseases and oral osteonecrosis: The role of gene-environment interactions

    Energy Technology Data Exchange (ETDEWEB)

    Baldi, D. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Izzotti, A. [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy); Bonica, P.; Pera, P. [Department of Medical, Biophysical, and Dentistry Sciences and Technologies, University of Genoa (Italy); Pulliero, A., E-mail: alessandra.pulliero@unige.it [Department of Health Sciences, University of Genoa, Via A. Pastore 1 (Italy)

    2009-07-10

    Chronic-degenerative dentistry diseases, including periodontal diseases and oral osteonecrosis, are widespread in human populations and represent a significant problem for public health. These diseases result from pathogenic mechanisms created by the interaction between environmental genotoxic risk-factors and genetic assets conferring individual susceptibility. Osteonecrosis occurs in subjects undergoing exposure to high doses of DNA-damaging agents for chemo- and radiotherapy of neoplastic diseases. In susceptible patients, ionizing radiation and biphosphonate-chemotherapy induce severe, progressive, and irreversible degeneration of facial bones, resulting in avascular necrosis of the jaw. This may also occur in patients receiving biphosphonate for osteoporosis therapy. Periodontal diseases include chronic, aggressive, and necrotizing periodontitis, often resulting in severe alteration of periodontal tissues and tooth loss. Cigarette smoking and chronic inflammation caused by specific bacteria are the main risk factors for periodontitis. Oxidative damage plays a fundamental pathogenic role, as established by detection of mitochondrial DNA damage in the gingival tissue of patients with periodontitis. Endogenous risk factors in dental diseases include polymorphisms for metabolic enzymes such as glutathione transferases M1 and T1, N-acetyl transferase 2, and CYP 1A1. Other genetic polymorphisms that confer susceptibility to dentistry diseases affect genes encoding metalloproteases (involved in periodontal tissue remodeling and degradation), cytokines (involved in inflammation), prothrombin, and DNA repair activities. These findings provide evidence that dentistry diseases are related to risk factors associated with environmental mutagenesis. This issue warrants future investigations aimed at improving oral health and preventing oral degenerative diseases using molecular and experimental approaches currently utilized in mutagenicity studies.

  18. Oral pregnancy tumor

    Directory of Open Access Journals (Sweden)

    Shailesh M Gondivkar

    2010-01-01

    Full Text Available Pyogenic granuloma is one of the inflammatory hyperplasias seen in the oral cavity. This term is a misnomer because the lesion is unrelated to infection and in reality arises in response to various stimuli such as low-grade local irritation, traumatic injury, or hormonal factors. It predominantly occurs in the second decade of life in young females, possibly because of the vascular effects of female hormones. Clinically, oral pyogenic granuloma is a smooth or lobulated exophytic lesion manifesting as small, red erythematous growth on a pedunculated or sometimes sessile base, which is usually hemorrhagic. Although excisional surgery is the treatment of choice , some other treatment protocols such as the use of Nd:YAG laser, flash lamp pulsed dye laser, cryosurgery, intralesional injection of ethanol or corticosteroids, and sodium tetradecyl sulfate sclerotherapy have been proposed. We present the case of a 25-year-old pregnant woman with large oral pyogenic granuloma.

  19. The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation

    DEFF Research Database (Denmark)

    Wandall, Hans H; Irazoqui, Fernando; Tarp, Mads Agervig

    2007-01-01

    Initiation of mucin-type O-glycosylation is controlled by a large family of UDP GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Most GalNAc-transferases contain a ricin-like lectin domain in the C-terminal end, which may confer GalNAc-glycopeptide substrate specificit...

  20. Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease

    Science.gov (United States)

    Grimm, Marcus O. W.; Grösgen, Sven; Rothhaar, Tatjana L.; Burg, Verena K.; Hundsdörfer, Benjamin; Haupenthal, Viola J.; Friess, Petra; Müller, Ulrike; Fassbender, Klaus; Riemenschneider, Matthias; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Lipids play an important role as risk or protective factors in Alzheimer's disease (AD), a disease biochemically characterized by the accumulation of amyloid beta peptides (Aβ), released by proteolytic processing of the amyloid precursor protein (APP). Changes in sphingolipid metabolism have been associated to the development of AD. The key enzyme in sphingolipid de novo synthesis is serine-palmitoyl-CoA transferase (SPT). In the present study we identified a new physiological function of APP in sphingolipid synthesis. The APP intracellular domain (AICD) was found to decrease the expression of the SPT subunit SPTLC2, the catalytic subunit of the SPT heterodimer, resulting in that decreased SPT activity. AICD function was dependent on Fe65 and SPTLC2 levels are increased in APP knock-in mice missing a functional AICD domain. SPTLC2 levels are also increased in familial and sporadic AD postmortem brains, suggesting that SPT is involved in AD pathology. PMID:21660213

  1. Yeast one-hybrid system used to identify the binding proteins for rat glutathione S-transferase P enhancer I.

    Science.gov (United States)

    Liao, Ming-Xiang; Liu, Dong-Yuan; Zuo, Jin; Fang, Fu-De

    2002-03-01

    To detect the trans-factors specifically binding to the strong enhancer element (GPEI) in the upstream of rat glutathione S-transferase P (GST-P) gene. Yeast one-hybrid system was used to screen rat lung MATCHMAKER cDNA library to identify potential trans-factors that can interact with core sequence of GPEI(cGPEI). Electrophoresis mobility shift assay (EMSA) was used to analyze the binding of transfactors to cGPEI. cDNA fragments coding for the C-terminal part of the transcription factor c-Jun and rat adenine nucleotide translocator (ANT) were isolated. The binding of c-Jun and ANT to GPEI core sequence were confirmed. Rat c-jun transcriptional factor and ANT may interact with cGPEI. They could play an important role in the induced expression of GST-P gene.

  2. Glutathione S-transferase of brown planthoppers (Nilaparvata lugens) is essential for their adaptation to gramine-containing host plants.

    Science.gov (United States)

    Sun, Xiao-Qin; Zhang, Mao-Xin; Yu, Jing-Ya; Jin, Yu; Ling, Bing; Du, Jin-Ping; Li, Gui-Hua; Qin, Qing-Ming; Cai, Qing-Nian

    2013-01-01

    Plants have evolved complex processes to ward off attacks by insects. In parallel, insects have evolved mechanisms to thwart these plant defenses. To gain insight into mechanisms that mediate this arms race between plants and herbivorous insects, we investigated the interactions between gramine, a toxin synthesized by plants of the family Gramineae, and glutathione S transferase (GST), an enzyme found in insects that is known to detoxify xenobiotics. Here, we demonstrate that rice (Oryza sativa), a hydrophytic plant, also produces gramine and that rice resistance to brown planthoppers (Nilaparvata lugens, BPHs) is highly associated with in planta gramine content. We also show that gramine is a toxicant that causes BPH mortality in vivo and that knockdown of BPH GST gene nlgst1-1 results in increased sensitivity to diets containing gramine. These results suggest that the knockdown of key detoxification genes in sap-sucking insects may provide an avenue for increasing their sensitivity to natural plant-associated defense mechanisms.

  3. Dynamic interplay between catalytic and lectin domains of GalNAc-transferases modulates protein O-glycosylation

    DEFF Research Database (Denmark)

    Lira-Navarrete, Erandi; de Las Rivas, Matilde; Compañón, Ismael

    2015-01-01

    the first crystal structures of complexes of GalNAc-T2 with glycopeptides that together with enhanced sampling molecular dynamics simulations demonstrate a cooperative mechanism by which the lectin domain enables free acceptor sites binding of glycopeptides into the catalytic domain. Atomic force microscopy......Protein O-glycosylation is controlled by polypeptide GalNAc-transferases (GalNAc-Ts) that uniquely feature both a catalytic and lectin domain. The underlying molecular basis of how the lectin domains of GalNAc-Ts contribute to glycopeptide specificity and catalysis remains unclear. Here we present...... and small-angle X-ray scattering experiments further reveal a dynamic conformational landscape of GalNAc-T2 and a prominent role of compact structures that are both required for efficient catalysis. Our model indicates that the activity profile of GalNAc-T2 is dictated by conformational heterogeneity...

  4. Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

    Science.gov (United States)

    Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

    2011-08-01

    To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  5. A SERS protocol as a potential tool to access 6-mercaptopurine release accelerated by glutathione-S-transferase.

    Science.gov (United States)

    Wang, Ying; Sun, Jie; Yang, Qingran; Lu, Wenbo; Li, Yan; Dong, Jian; Qian, Weiping

    2015-11-21

    The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.

  6. The identification and characterisation of a functional interaction between arginyl-tRNA-protein transferase and topoisomerase II

    International Nuclear Information System (INIS)

    Barker, Catherine R.; Mouchel, Nathalie A.P.; Jenkins, John R.

    2006-01-01

    Topoisomerase II is required for the viability of all eukaryotic cells. It plays important roles in DNA replication, recombination, chromosome segregation, and the maintenance of the nuclear scaffold. Proteins that interact with and regulate this essential enzyme are of great interest. To investigate the role of proteins interacting with the N-terminal domain of the Saccharomyces cerevisiae topoisomerase II, we used a yeast two-hybrid protein interaction screen. We identified an interaction between arginyl-tRNA-protein transferase (Ate1) and the N-terminal domain of the S. cerevisiae topoisomerase II, including the potential site of interaction. Ate1 is a component of the N-end rule protein degradation pathway which targets proteins for degradation. We also propose a previously unidentified role for Ate1 in modulating the level of topoisomerase II through the cell cycle

  7. Shared Oral Care

    DEFF Research Database (Denmark)

    Hede, Børge; Elmelund Poulsen,, Johan; Christophersen, Rasmus

    2014-01-01

    Shared Oral Care - Forebyggelse af orale sygdomme på plejecentre Introduktion og formål: Mangelfuld mundhygiejne hos plejekrævende ældre er et alment og veldokumenteret sundhedsproblem, der kan føre til massiv udvikling af tandsygdomme, og som yderligere kan være medvirkende årsag til alvorlige...... ressourceanvendelse er muligt at skabe en betydeligt forbedret mundhygiejne hos plejekrævende ældre Key words: Geriatric dentistry, nursing home, community health services, prevention, situated learning...

  8. Oral lichen planus

    International Nuclear Information System (INIS)

    Rasool, S.; Katpar, S.; Ali, A.

    2007-01-01

    Lichen planus is a mucocutaneous dermatological disorder, with intraoral manifestation. Skin lesions prevail with oral mucosal lesions. Prevalence of lichen planus, as an oral pre-malignant lesion, is 1-2 % population. Lateral border, dorsal tongue, gingiva, hard palate and vermilion border are common sites and lesions appear as reticular, plaque-like and papular intraoral types. Skin presents with pururitic, polygonal papules. Atrophic and erosive are the known intraoral pre-malignant types. A case report is presented, which responded well to steroid therapy. (author)

  9. Identification and suppression of the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase in Zea mays L.

    Science.gov (United States)

    Marita, Jane M; Hatfield, Ronald D; Rancour, David M; Frost, Kenneth E

    2014-06-01

    Grasses, such as Zea mays L. (maize), contain relatively high levels of p-coumarates (pCA) within their cell walls. Incorporation of pCA into cell walls is believed to be due to a hydroxycinnamyl transferase that couples pCA to monolignols. To understand the role of pCA in maize development, the p-coumaroyl CoA:hydroxycinnamyl alcohol transferase (pCAT) was isolated and purified from maize stems. Purified pCAT was subjected to partial trypsin digestion, and peptides were sequenced by tandem mass spectrometry. TBLASTN analysis of the acquired peptide sequences identified a single full-length maize cDNA clone encoding all the peptide sequences obtained from the purified enzyme. The cDNA clone was obtained and used to generate an RNAi construct for suppressing pCAT expression in maize. Here we describe the effects of suppression of pCAT in maize. Primary screening of transgenic maize seedling leaves using a new rapid analytical platform was used to identify plants with decreased amounts of pCA. Using this screening method, mature leaves from fully developed plants were analyzed, confirming reduced pCA levels throughout plant development. Complete analysis of isolated cell walls from mature transgenic stems and leaves revealed that lignin levels did not change, but pCA levels decreased and the lignin composition was altered. Transgenic plants with the lowest levels of pCA had decreased levels of syringyl units in the lignin. Thus, altering the levels of pCAT expression in maize leads to altered lignin composition, but does not appear to alter the total amount of lignin present in the cell walls. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  10. Synergistic and independent actions of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wang

    2015-04-01

    Full Text Available All types of small RNAs in plants, piwi-interacting RNAs (piRNAs in animals and a subset of siRNAs in Drosophila and C. elegans are subject to HEN1 mediated 3' terminal 2'-O-methylation. This modification plays a pivotal role in protecting small RNAs from 3' uridylation, trimming and degradation. In Arabidopsis, HESO1 is a major enzyme that uridylates small RNAs to trigger their degradation. However, U-tail is still present in null hen1 heso1 mutants, suggesting the existence of (an enzymatic activities redundant with HESO1. Here, we report that UTP: RNA uridylyltransferase (URT1 is a functional paralog of HESO1. URT1 interacts with AGO1 and plays a predominant role in miRNA uridylation when HESO1 is absent. Uridylation of miRNA is globally abolished in a hen1 heso1 urt1 triple mutant, accompanied by an extensive increase of 3'-to-5' trimming. In contrast, disruption of URT1 appears not to affect the heterochromatic siRNA uridylation. This indicates the involvement of additional nucleotidyl transferases in the siRNA pathway. Analysis of miRNA tailings in the hen1 heso1 urt1 triple mutant also reveals the existence of previously unknown enzymatic activities that can add non-uridine nucleotides. Importantly, we show HESO1 may also act redundantly with URT1 in miRNA uridylation when HEN1 is fully competent. Taken together, our data not only reveal a synergistic action of HESO1 and URT1 in the 3' uridylation of miRNAs, but also independent activities of multiple terminal nucleotidyl transferases in the 3' tailing of small RNAs and an antagonistic relationship between uridylation and trimming. Our results may provide further insight into the mechanisms of small RNA 3' end modification and stability control.

  11. Phylogenetic characterization of Clonorchis sinensis proteins homologous to the sigma-class glutathione transferase and their differential expression profiles.

    Science.gov (United States)

    Bae, Young-An; Kim, Jeong-Geun; Kong, Yoon

    2016-01-01

    Glutathione transferase (GST) is one of the major antioxidant proteins with diverse supplemental activities including peroxidase, isomerase, and thiol transferase. GSTs are classified into multiple classes on the basis of their primary structures and substrate/inhibitor specificity. However, the evolutionary routes and physiological environments specific to each of the closely related bioactive enzymes remain elusive. The sigma-like GSTs exhibit amino acid conservation patterns similar to the prostaglandin D synthases (PGDSs). In this study, we analyzed the phylogenetic position of the GSTs of the biocarcinogenic liver fluke, Clonorchis sinensis. We also observed induction profile of the GSTs in association with the parasite's maturation and in response to exogenous oxidative stresses, with special attention to sigma-class GSTs and PGDSs. The C. sinensis genome encoded 12 GST protein species, which were separately assigned to cytosolic (two omega-, one zeta-, two mu-, and five sigma-class), mitochondrial (one kappa-class), and microsomal (one membrane-associated proteins in eicosanoid and glutathione metabolism-like protein) GST families. Multiple sigma GST (or PGDS) orthologs were also detected in Opisthorchis viverrini. Other trematode species possessed only a single sigma-like GST gene. A phylogenetic analysis demonstrated that one of the sigma GST lineages duplicated in the common ancestor of trematodes were specifically expanded in the opisthorchiids, but deleted in other trematodes. The induction profiles of these sigma GST genes along with the development and aging of C. sinensis, and against various exogenous chemical stimuli strongly suggest that the paralogous sigma GST genes might be undergone specialized evolution to cope with the diverse hostile biochemical environments within the mammalian hepatobiliary ductal system. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Maize w3 disrupts homogentisate solanesyl transferase (ZmHst) and reveals a plastoquinone-9 independent path for phytoene desaturation and tocopherol accumulation in kernels

    Science.gov (United States)

    Maize white seedling 3 (w3) has been used to study carotenoid deficiency for almost 100 years, although its genetic basis remained unknown. We show here that w3 phenotype is caused by disruption of homogentisate solanesyl transferase (HST), which catalyzes the first committed step in plastoquinone-9...

  13. Succinyl-CoA:acetoacetate transferase deficiency : identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K E; Wanders, R J; Ruiter, J P; Ijlst, L; Visser, G; Reitsma-Bierens, W C; Heijmans, Hugo; Reijngoud, D J; Smit, G P

    1997-01-01

    UNLABELLED: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis,

  14. Effects of Deletion of the Streptococcus pneumoniae Lipoprotein Diacylglyceryl Transferase Gene lgt on ABC Transporter Function and on Growth In Vivo.

    NARCIS (Netherlands)

    Chimalapati, S.; Cohen, J.M.; Camberlein, E.; Macdonald, N.; Durmort, C.; Vernet, T.; Hermans, P.W.M.; Mitchell, T.; Brown, J.S.

    2012-01-01

    Lipoproteins are an important class of surface associated proteins that have diverse roles and frequently are involved in the virulence of bacterial pathogens. As prolipoproteins are attached to the cell membrane by a single enzyme, prolipoprotein diacylglyceryl transferase (Lgt), deletion of the

  15. Succinyl-CoA:acetoacetate transferase deficiency: identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K. E.; Wanders, R. J.; Ruiter, J. P.; IJlst, L.; Visser, G.; Reitsma-Bierens, W. C.; Heymans, H. S.; Reijngoud, D. J.; Smit, G. P.

    1997-01-01

    We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis, and

  16. The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma

    DEFF Research Database (Denmark)

    Rogers, A J; Brasch-Andersen, C; Ionita-Laza, I

    2009-01-01

    BACKGROUND: The glutathione S-transferase M1 (GSTM1)-null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress. OBJECTIVE: To exp...

  17. Quantum Mechanical/Molecular Mechanical Free Energy Simulations of the Glutathione S-Transferase (M1-1) Reaction with Phenanthrene 9,10-Oxide

    NARCIS (Netherlands)

    Ridder, L.; Rietjens, I.M.C.M.; Vervoort, J.J.M.; Mulholland, A.J.

    2002-01-01

    Glutathione S-transferases (GSTs) play an important role in the detoxification of xenobiotics in mammals. They catalyze the conjugation of glutathione to a wide range of electrophilic compounds. Phenanthrene 9,10-oxide is a model substrate for GSTs, representing an important group of epoxide

  18. Succinyl-CoA:acetoacetate transferase deficiency : identification of a new patient with a neonatal onset and review of the literature

    NARCIS (Netherlands)

    Niezen-Koning, K E; Wanders, R J; Ruiter, J P; Ijlst, L; Visser, G; Reitsma-Bierens, W C; Heijmans, Hugo; Reijngoud, D J; Smit, G P

    UNLABELLED: We describe the clinical symptoms and biochemical findings of a patient with succinyl-CoA:acetoacetate transferase deficiency who presented in the neonatal period and review the current literature on this subject. Our patient was initially suspected to have distal renal tubular acidosis,

  19. The role of the glutathione S-transferase genes GSTT1, GSTM1, and GSTP1 in acetaminophen-poisoned patients

    DEFF Research Database (Denmark)

    Buchard, Anders; Eefsen, Martin; Semb, Synne

    2012-01-01

    The aim of this study was to assess if genetic variants in the glutathione-S-transferase genes GST-T1, M1, and P1 reflect risk factors in acetaminophen (APAP)-poisoned patients assessed by investigation of the relation to prothrombin time (PT), which is a sensitive marker of survival in these pat...

  20. The association of glutathione S-transferase GSTT1 and GSTM1 gene polymorphism with pseudoexfoliative glaucoma in a Pakistani population.

    NARCIS (Netherlands)

    Khan, M.I.; Micheal, S.; Akhtar, F.; Ahmed, W.; Ijaz, B.; Ahmed, A.; Qamar, R.

    2010-01-01

    PURPOSE: The aim of the present study was to investigate the association of glutathione S-transferase GSTT1 and GSTM1 genotypes with pseudoexfoliative glaucoma (PEXG) in a group of Pakistani patients. METHODS: Multiplex polymerase chain reaction was used to study the GSTT1 and GSTM1 polymorphisms in

  1. Differential transcription of cytochrome P450s and glutathione S transferases in DDT-susceptible and resistant Drosophila melanogaster strains in response to DDT and oxidative stress

    Science.gov (United States)

    Metabolic DDT resistance in Drosophila melanogaster has previously been associated with constitutive over-transcription of cytochrome P450s. Increased P450 activity has also been associated with increased oxidative stress. In contrast, over-transcription of glutathione S transferases (GSTs) has been...

  2. Inequalities in oral health and oral health promotion

    OpenAIRE

    Moysés, Samuel Jorge

    2012-01-01

    This article offers a critical review of the problem of inequalities in oral health and discusses strategies for disease prevention and oral health promotion. It shows that oral health is not merely a result of individual biological, psychological, and behavioral factors; rather, it is the sum of collective social conditions created when people interact with the social environment. Oral health status is directly related to socioeconomic position across the socioeconomic gradient in almost all...

  3. Probiotics as oral health biotherapeutics.

    Science.gov (United States)

    Saha, Shyamali; Tomaro-Duchesneau, Catherine; Tabrizian, Maryam; Prakash, Satya

    2012-09-01

    Oral health is affected by its resident microorganisms. Three prominent oral disorders are dental caries, gingivitis and periodontitis, with the oral microbiota playing a key role in the initiation/progression of all three. Understanding the microbiota and the diseases they may cause is critical to the development of new therapeutics. This review is focused on probiotics for the prevention and/or treatment of oral diseases. This review describes the oral ecosystem and its correlation with oral health/disease. The pathogenesis and current prevention/treatment strategies of periodontal diseases (PD) and dental caries (DC) are depicted. An introduction of probiotics is followed by an analysis of their role in PD and DC, and their potential role(s) in oral health. Finally, a discussion ensues on the future research directions and limitations of probiotics for oral health. An effective oral probiotic formulation should contribute to the prevention/treatment of microbial diseases of the oral cavity. Understanding the oral microbiota's role in oral disease is important for the development of a therapeutic to prevent/treat dental diseases. However, investigations into clinical efficacy, delivery/dose optimization, mechanism(s) of action and other related parameters are yet to be fully explored. Keeping this in mind, investigations into oral probiotic therapies are proving promising.

  4. Oral hygiene practices and risk of oral leukoplakia | Macigo | East ...

    African Journals Online (AJOL)

    Objective: To determine the influence of oral hygiene habits and practices on the risk of developing oral leukoplakia. Design: Case control study. Setting: Githongo sublocation in Meru District. Subjects: Eighty five cases and 141 controls identified in a house-to-house screening. Results: The relative risk (RR) of oral ...

  5. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond

    Directory of Open Access Journals (Sweden)

    Jumpei Washio

    2016-06-01

    Full Text Available Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the ‘Warburg effect’. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  6. Oral Hygiene and Oral Flora Evaluation in Psychiatric Patients in ...

    African Journals Online (AJOL)

    Conclusions: The oral hygiene of most patients was insufficient. The presence of Gram‑negative Bacilli growth in the oral flora can be explained by poor hand hygiene. These findings suggest that it is useful to educate individuals about oral hygiene and hand hygiene and to inform the staff and families about this issue.

  7. The New Orality: Oral Characteristics of Computer-Mediated Communication.

    Science.gov (United States)

    Ferris, Sharmila Pixy; Montgomery, Maureen

    1996-01-01

    Considers the characteristics of orality and literacy developed in the work of scholars such as Walter Ong to consider computer-mediated communication (CMC) as the potential site of a "new orality" which is neither purely oral or literate. Notes that the medium of CMC is writing, which has traditionally represented the…

  8. Metabolomic Studies of Oral Biofilm, Oral Cancer, and Beyond.

    Science.gov (United States)

    Washio, Jumpei; Takahashi, Nobuhiro

    2016-06-02

    Oral diseases are known to be closely associated with oral biofilm metabolism, while cancer tissue is reported to possess specific metabolism such as the 'Warburg effect'. Metabolomics might be a useful method for clarifying the whole metabolic systems that operate in oral biofilm and oral cancer, however, technical limitations have hampered such research. Fortunately, metabolomics techniques have developed rapidly in the past decade, which has helped to solve these difficulties. In vivo metabolomic analyses of the oral biofilm have produced various findings. Some of these findings agreed with the in vitro results obtained in conventional metabolic studies using representative oral bacteria, while others differed markedly from them. Metabolomic analyses of oral cancer tissue not only revealed differences between metabolomic profiles of cancer and normal tissue, but have also suggested a specific metabolic system operates in oral cancer tissue. Saliva contains a variety of metabolites, some of which might be associated with oral or systemic disease; therefore, metabolomics analysis of saliva could be useful for identifying disease-specific biomarkers. Metabolomic analyses of the oral biofilm, oral cancer, and saliva could contribute to the development of accurate diagnostic, techniques, safe and effective treatments, and preventive strategies for oral and systemic diseases.

  9. Imaging in oral cancers

    International Nuclear Information System (INIS)

    Arya, Supreeta; Chaukar, Devendra; Pai, Prathamesh

    2012-01-01

    Oral cavity squamous cell cancers form a significant percentage of the cancers seen in India. While clinical examination allows direct visualization, it cannot evaluate deep extension of disease. Cross-sectional imaging has become the cornerstone in the pretreatment evaluation of these cancers and provides accurate information about the extent and depth of disease that can help decide the appropriate management strategy and indicate prognosis. Early cancers are treated with a single modality, either surgery or radiotherapy while advanced cancers are offered a combination of surgery, radiotherapy and chemotherapy. Imaging can decide resectability, help plan the precise extent of resection, and indicate whether organ conservation therapy should be offered. Quality of life issues necessitate preservation of form and function and pretreatment imaging helps plan appropriate reconstruction and counsel patients regarding lifestyle changes. Oral cavity has several subsites and the focus of the review is squamous cancers of the gingivobuccal region, oral tongue and retromolar trigone as these are most frequently encountered in the subcontinent. References for this review were identified by searching Medline and PubMed databases. Only articles published in English language literature were selected. This review aims to familiarize the radiologist with the relevant anatomy of the oral cavity, discuss the specific issues that influence prognosis and management at the above subsites, the optimal imaging methods, the role of imaging in accurately staging these cancers and in influencing management. A checklist for reporting will emphasize the information to be conveyed by the radiologist

  10. IDEA: Stimulating Oral Production.

    Science.gov (United States)

    Easley, Jacob J.

    1995-01-01

    Presents daily activities that facilitate complete sentence response, promote oral production, and aid the learning of vocabulary in foreign-language classes. Because speech is the primary form of communication in the foreign-language classroom, it is important to stimulate students to converse as soon as possible. (Author/CK)

  11. Fluoride and Oral Health

    DEFF Research Database (Denmark)

    O'Mullane, D M; Baez, R J; Jones, S

    2016-01-01

    and strategies is noteworthy. This updated version of ‘Fluoride and Oral Health’ has adopted an evidence-based approach to its commentary on the different fl uoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published...

  12. Oral Health and Women

    Centers for Disease Control (CDC) Podcasts

    2009-05-12

    This women's health podcast focuses on the importance of maintaining good oral health during pregnancy.  Created: 5/12/2009 by Office of Women’s Health (OWH) and National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/12/2009.

  13. History of oral contraception.

    Science.gov (United States)

    Dhont, Marc

    2010-12-01

    On the 50th birthday of the pill, it is appropriate to recall the milestones which have led to its development and evolution during the last five decades. The main contraceptive effect of the pill being inhibition of ovulation, it may be called a small miracle that this drug was developed long before the complex regulation of ovulation and the menstrual cycle was elucidated. Another stumbling block on its way was the hostile climate with regard to contraception that prevailed at the time. Animal experiments on the effect of sex steroids on ovulation, and the synthesis of sex steroids and orally active analogues were the necessary preliminaries. We owe the development of oral contraceptives to a handful of persons: two determined feminists, Margaret Sanger and Katherine McCormick; a biologist, Gregory Pincus; and a gynaecologist, John Rock. Soon after the introduction of the first pills, some nasty and life-threatening side effects emerged, which were due to the high doses of sex steroids. This led to the development of new preparations with reduced oestrogen content, progestins with more specific action, and alternative administration routes. Almost every decade we have witnessed a breakthrough in oral contraception. Social and moral objections to birth control have gradually disappeared and, notwithstanding some pill scares, oral contraceptives are now one of the most used methods of contraception. Finally, all's well that ends well: recent reports have substantiated the multiple noncontraceptive health benefits paving the way for a bright future for this 50-year-old product.

  14. Oral Lichen Planus.

    Science.gov (United States)

    Ion, Daniela I; Setterfield, Jane F

    2016-02-01

    Lichen planus (LP) is a relatively common autoimmune T-cell-mediated disease of unknown aetiology affecting the mucous membranes, skin and nails. Its prevalence varies between 0.5 and 2.2% of the population in epidemiological studies with a peak incidence in the 30-60 years range and with a female predominance of 2:1. Mucosal lichen planus tends to follow a chronic course with acute exacerbations. Spontaneous remission of oral lichen planus (OLP) is uncommon, and indeed mucosal LP may become worse with time. In contrast, cutaneous lichen planus may follow a milder clinical course though some variants may be severe such as those affecting the palms and soles and the scalp and the genital tract in females (vulvovaginal gingival LP) where scarring leads to significant complications. It is important to identify those cases that may be drug induced or be associated with a contact allergic or irritant reaction (lichenoid reaction) or the rarer oral presentation of discoid lupus erythematosus. There is a very small risk of malignancy (approximately 1:200 patients/year) associated with oral lichen planus; thus patients should be informed that long term monitoring via their general dental practitioner is appropriate. This review will focus on the clinical presentation and management of oral lichen planus.

  15. Oral lichen planus

    Directory of Open Access Journals (Sweden)

    Šehalić Meliha

    2014-01-01

    Full Text Available 29 - year Lichen planus is a chronic, inflammatory, autoimmune skin disease, that is often manifested, except on the skin, in the oral cavity in a variety of clinical forms. The prevalence of the disease in the general population is about 1-2%. Etiopathogenesis is not still well understood. Histopathology, in addition to the basic methods, anamnesis and physical examination, is vital for proper diagnosis of oral lichen planus (OLP. Very diverse and loaded histological findings are common for all forms of oral lichen planus. We reported the case of oral lichen planus in a 49 years old male patient, who presented to the Dentistry clinic of Medical faculty of Priština with burning and itching symptoms and changes in the buccal mucosa. Histopathological analysis of biopsy tissue conformed clinical diagnosis of lichen planus. Due to the possibility for malignant transformation of lesions, the long-term follow-up of patients with this disease is of great importance.

  16. Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents.

    Science.gov (United States)

    Nijampatnam, Bhavitavya; Casals, Luke; Zheng, Ruowen; Wu, Hui; Velu, Sadanandan E

    2016-08-01

    Streptococcus mutans has been implicated as the major etiological agent in the initiation and the development of dental caries due to its robust capacity to form tenacious biofilms. Ideal therapeutics for this disease will aim to selectively inhibit the biofilm formation process while preserving the natural bacterial flora of the mouth. Several studies have demonstrated the efficacies of flavonols on S. mutans biofilms and have suggested the mechanism of action through their effect on S. mutans glucosyltransferases (Gtfs). These enzymes metabolize sucrose into water insoluble and soluble glucans, which are an integral measure of the dental caries pathogenesis. Numerous studies have shown that flavonols and polyphenols can inhibit Gtf and biofilm formation at millimolar concentrations. We have screened a group of 14 hydroxychalcones, synthetic precursors of flavonols, in an S. mutans biofilm assay. Several of these compounds emerged to be biofilm inhibitors at low micro-molar concentrations. Chalcones that contained a 3-OH group on ring A exhibited selectivity for biofilm inhibition. Moreover, we synthesized 6 additional analogs of the lead compound and evaluated their potential activity and selectivity against S. mutans biofilms. The most active compound identified from these studies had an IC50 value of 44μM against biofilm and MIC50 value of 468μM against growth displaying >10-fold selectivity inhibition towards biofilm. The lead compound displayed a dose dependent inhibition of S. mutans Gtfs. The lead compound also did not affect the growth of two commensal species (Streptococcus sanguinis and Streptococcus gordonii) at least up to 200μM, indicating that it can selectively inhibit cariogenic biofilms, while leaving commensal and/or beneficial microbes intact. Thus non-toxic compounds have the potential utility in public oral health regimes. Copyright © 2016. Published by Elsevier Ltd.

  17. Antibiotics and oral contraceptives.

    Science.gov (United States)

    DeRossi, Scott S; Hersh, Elliot V

    2002-10-01

    With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution

  18. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Extensive education and training in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral ... Extensive education and training in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral ...

  19. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Contact Find a Surgeon What We Do Anesthesia Anesthesia Oral and maxillofacial surgeons are extensively trained to ... and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons are extensively trained to ...

  20. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... mouth and gums to improve function, appearance and oral health. Click here to find out more. Facial Cosmetic ... mouth and gums to improve function, appearance and oral health. Click here to find out more. Facial Cosmetic ...

  1. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral and maxillofacial surgeons. The experts in face, mouth and jaw surgery.™ What We Do Who We ... surgically treat the soft tissues of the face, mouth and gums to improve function, appearance and oral ...

  2. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and Neck Pathology Close to 49,750 Americans will be diagnosed with oral or pharyngeal cancer this ... and Neck Pathology Close to 49,750 Americans will be diagnosed with oral or pharyngeal cancer this ...

  3. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... tissues of the face, mouth and gums to improve function, appearance and oral health. Click here to ... tissues of the face, mouth and gums to improve function, appearance and oral health. Click here to ...

  4. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and training in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral and maxillofacial ... and training in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral and maxillofacial ...

  5. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and gums to improve function, appearance and oral health. Click here to find out more. Facial Cosmetic ... and gums to improve function, appearance and oral health. Click here to find out more. Facial Cosmetic ...

  6. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral and maxillofacial surgeon to ... in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral and maxillofacial surgeon to ...

  7. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ... Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed ...

  8. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... for further information Your oral and maxillofacial surgeon (OMS) is the expert for diagnosing and surgically treating ... late in its development. Your family dentist or OMS is in the best position to detect oral ...

  9. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed with ... and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed with ...

  10. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... education and training in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral and ... education and training in surgical procedures involving skin, muscle, bone and cartilage finely attune the oral and ...

  11. Elevated gamma glutamyl transferase levels are associated with the location of acute pulmonary embolism. Cross-sectional evaluation in hospital setting

    Directory of Open Access Journals (Sweden)

    Ozge Korkmaz

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: The location of embolism is associated with clinical findings and disease severity in cases of acute pulmonary embolism. The level of gamma-glutamyl transferase increases under oxidative stress-related conditions. In this study, we investigated whether gamma-glutamyl transferase levels could predict the location of pulmonary embolism. DESIGN AND SETTING: Hospital-based cross-sectional study at Cumhuriyet University, Sivas, Turkey. METHODS : 120 patients who were diagnosed with acute pulmonary embolism through computed tomography-assisted pulmonary angiography were evaluated. They were divided into two main groups (proximally and distally located, and subsequently into subgroups according to thrombus localization as follows: first group (thrombus in main pulmonary artery; n = 9; second group (thrombus in main pulmonary artery branches; n = 71; third group (thrombus in pulmonary artery segmental branches; n = 34; and fourth group (thrombus in pulmonary artery subsegmental branches; n = 8. RESULTS : Gamma-glutamyl transferase levels on admission, heart rate, oxygen saturation, right ventricular dilatation/hypokinesia, pulmonary artery systolic pressure and cardiopulmonary resuscitation requirement showed prognostic significance in univariate analysis. The multivariate logistic regression model showed that gamma-glutamyl transferase level on admission (odds ratio, OR = 1.044; 95% confidence interval, CI: 1.011-1.079; P = 0.009 and pulmonary artery systolic pressure (OR = 1.063; 95% CI: 1.005-1.124; P = 0.033 remained independently associated with proximally localized thrombus in pulmonary artery. CONCLUSIONS : The findings revealed a significant association between increased existing embolism load in the pulmonary artery and increased serum gamma-glutamyl transferase levels.

  12. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

    Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

  13. Oral yeast colonization throughout pregnancy

    OpenAIRE

    Rio, Rute; Sim?es-Silva, Liliana; Garro, Sofia; Silva, M?rio-Jorge; Azevedo, ?lvaro; Sampaio-Maia, Benedita

    2017-01-01

    Background Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with n...

  14. Oral Lichen Planus in Children

    OpenAIRE

    Mohan Das, Usha; JP, Beena

    2009-01-01

    Oral lichen planus which is one of the most common oral mucosal diseases in adults, it has been rarely described in children. There are very reports in the literature regarding oral lichen planus in children, here we report a case of intraoral lesions of lichen planus. Lichen planus should be considered in the differential diagnosis of hyperkeratotic or erosive lesions of the oral mucosa in children.

  15. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  16. Oral Biopsy: A Dental Gawk

    African Journals Online (AJOL)

    Sir,. Dermatologists are often confronted with neoplasms and diseases of the oral cavity. Although many may be reluctant to perform oral surgical procedures, a biopsy is often needed to establish a definitive diagnosis, and biopsy of the oral cavity is a safe and useful technique that can be easily employed by dermatologists.

  17. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... cancer of the head, neck and mouth. The Oral Cancer Foundation estimates that close to 42,000 Americans ... diagnosed with oral or pharyngeal cancer this year. Oral cancer’s mortality is particularly high, not because it is ...

  18. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Americans will be diagnosed with oral or pharyngeal cancer this year. Oral cancer’s mortality is particularly high, not because it is ... OMS is in the best position to detect oral cancer during your routine dental examinations. Don't risk ...

  19. Oral health: equity and social determinants

    DEFF Research Database (Denmark)

    Kwan, Stella; Petersen, Poul Erik

    2010-01-01

    This book chapter discusses the social determinants of oral health, and identifies interventions that have been, or can be, used in addressing oral health inequities (e.g. oral health promotion, education programmes, improving access to oral health care)....

  20. Scandinavian Fellowship for Oral Pathology and Oral Medicine

    DEFF Research Database (Denmark)

    Kragelund, Camilla; Reibel, J; Hietanen, J

    2012-01-01

    as new approaches, treatments and diagnostic possibilities develop. Likewise, the role of the dentist in the community changes and may vary in different countries. As members of the Scandinavian Fellowship for Oral Pathology and Oral Medicine and subject representatives of oral pathology and oral......In Scandinavia, as in many European countries, most patients consult their general dentist once a year or more. This gives the dentist a unique opportunity and an obligation to make an early diagnosis of oral diseases, which is beneficial for both the patient and the society. Thus, the dentist must...... medicine, we feel obliged to contribute to the discussion of how the guidelines of the dental curriculum support the highest possible standards of dental education. This article is meant to delineate a reasonable standard of oral pathology and oral medicine in the European dental curriculum and to guide...

  1. Effect of Fixed Metallic Oral Appliances on Oral Health.

    Science.gov (United States)

    Alnazzawi, Ahmad

    2018-01-01

    There is a substantial proportion of the population using fixed metallic oral appliances, such as crowns and bridges, which are composed of various dental alloys. These restorations may be associated with a number of effects on oral health with variable degrees of severity, to review potential effects of using fixed metallic oral appliances, fabricated from various alloys. The MEDLINE/PubMed database was searched using certain combinations of keywords related to the topic. The search revealed that burning mouth syndrome, oral pigmentation, hypersensitivity and lichenoid reactions, and genotoxic and cytotoxic effects are the major potential oral health changes associated with fixed prosthodontic appliances. Certain oral disorders are associated with the use of fixed metallic oral appliances. Patch test is the most reliable method that can be applied for identifying metal allergy, and the simultaneous use of different alloys in the mouth is discouraged.

  2. An orthodontic oral appliance.

    Science.gov (United States)

    Marklund, Marie; Legrell, Per Erik

    2010-11-01

    This pilot study was performed to test the hypothesis that an orthodontic oral appliance (OA) that is designed to work against the backwardly directed forces on the upper incisors may counteract the reduction in overjet from these devices. Thirty patients with normal bites, good oral health, and milder sleep apnea were randomized to treatment with either OAs or orthodontic OAs. Bite changes were evaluated on plaster casts and radiographs and by questionnaires after a mean of 2.4 years in 19 frequent users. Four of nine patients in the orthodontic OA group increased their overjet by > or =0.4 mm, while none of the 10 patients in the OA group experienced that effect. Only the orthodontic OA increases the overjet; this design may therefore be beneficial to patients at risk of negative effects on their bite during OA treatment.

  3. Immunologically mediated oral diseases.

    Science.gov (United States)

    Jimson, Sudha; Balachader, N; Anita, N; Babu, R

    2015-04-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  4. Immunologically mediated oral diseases

    Directory of Open Access Journals (Sweden)

    Sudha Jimson

    2015-01-01

    Full Text Available Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect immunoflouresence, immune precipitation and immunoblotting. Therapeutic agents should be selected after thorough evaluation of immune status through a variety of tests and after determining any aggravating or provoking factors. Early and appropriate diagnosis is important for proper treatment planning contributing to better prognosis and better quality of life of patient.

  5. Fluoride and Oral Health.

    Science.gov (United States)

    O'Mullane, D M; Baez, R J; Jones, S; Lennon, M A; Petersen, P E; Rugg-Gunn, A J; Whelton, H; Whitford, G M

    2016-06-01

    The discovery during the first half of the 20th century of the link between natural fluoride, adjusted fluoride levels in drinking water and reduced dental caries prevalence proved to be a stimulus for worldwide on-going research into the role of fluoride in improving oral health. Epidemiological studies of fluoridation programmes have confirmed their safety and their effectiveness in controlling dental caries. Major advances in our knowledge of how fluoride impacts the caries process have led to the development, assessment of effectiveness and promotion of other fluoride vehicles including salt, milk, tablets, toothpaste, gels and varnishes. In 1993, the World Health Organization convened an Expert Committee to provide authoritative information on the role of fluorides in the promotion of oral health throughout the world (WHO TRS 846, 1994). This present publication is a revision of the original 1994 document, again using the expertise of researchers from the extensive fields of knowledge required to successfully implement complex interventions such as the use of fluorides to improve dental and oral health. Financial support for research into the development of these new fluoride strategies has come from many sources including government health departments as well as international and national grant agencies. In addition, the unique role which industry has played in the development, formulation, assessment of effectiveness and promotion of the various fluoride vehicles and strategies is noteworthy. This updated version of 'Fluoride and Oral Health' has adopted an evidence-based approach to its commentary on the different fluoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published in peer reviewed literature.

  6. Per-oral cholangioscopy

    OpenAIRE

    Monga, Amitabh; Ramchandani, Mohan; Reddy, D Nageshwar

    2011-01-01

    Direct endoscopic views of bile duct have been described in literature since the 1970s. Since then rapid strides have been made with the advent of technologically advanced systems with better image quality and maneuverability. The single operator semi-disposable per-oral cholangioscope and other novel methods such as the cholangioscopy access balloon are likely to revolutionize this field. Even though cholangioscopy is currently used primarily for characterization of indeterminate strictures ...

  7. Challenges in Comparative Oral Epic

    Directory of Open Access Journals (Sweden)

    John Miles Foley

    2012-10-01

    Full Text Available Originally written in 2001 and subsequently published in China, this collaborative essay explores five questions central to comparative oral epic with regard to Mongolian, South Slavic, ancient Greek, and Old English traditions: “What is a poem in oral epic tradition?” “What is a typical scene or theme in oral epic tradition?” “What is a poetic line in oral epic tradition?” “What is a formula in an oral epic tradition?” “What is the register in oral epic poetry?” Now available for the first time in English, this essay reflects a foundational stage of what has become a productive and long-term collaboration between the Center for Studies in Oral Tradition and the Institute of Ethnic Literature of the Chinese Academy of Social Sciences.

  8. Fractal analysis in oral leukoplakia

    Directory of Open Access Journals (Sweden)

    Prashant Bhai Pandey

    2015-01-01

    Full Text Available Introduction: Fractal analysis (FA quantifies complex geometric structures by generating a fractal dimension (FD, which can measure the complexity of mucosa. FA is a quantitative tool used to measure the complexity of self-similar or semi-self-similar structures. Aim and Objective: The study was done to perform the FA of oral mucosa with keratotic changes, as it is also made up of self-similar tissues, and thus, its FD can be calculated. Results: In oral leukoplakia, keratinization increases the complexity of mucosa, which denotes fractal geometry. We evaluated and compared pretreated and post-treated oral leukoplakia in 50 patients with clinically proven oral leukoplakia and analyzed the normal oral mucosa and lesional or keratinized mucosa in oral leukoplakia patients through FA using box counting method. Conclusion: FA using the fractal geometry is an efficient, noninvasive prediction tool for early detection of oral leukoplakia and other premalignant conditions in patients.

  9. Oral cancer screening practices of oral health professionals in Australia.

    Science.gov (United States)

    Mariño, Rodrigo; Haresaku, Satoru; McGrath, Roisin; Bailey, Denise; Mccullough, Michael; Musolino, Ross; Kim, Boaz; Chinnassamy, Alagesan; Morgan, Michael

    2017-12-15

    To evaluate oral cancer-related screening practices of Oral Health Professionals (OHPs - dentists, dental hygienists, dental therapists, and oral health therapists) practising in Victoria, Australia. A 36-item survey was distributed to 3343 OHPs. Items included socio-demographic and work-related characteristics; self-assessed knowledge of oral cancer; perceived level of confidence in discussing oral health behaviors with patients; oral cancer screening practices; and self-evaluated need for additional training on screening procedures for oral cancer. A total of 380 OHPs responded this survey, achieving an overall response rate of 9.4%. Forty-five were excluded from further analysis. Of these 335 OHP, 72% were dentists; (n = 241); either GDP or Dental Specialists; 13.7% (n = 46) were dental hygienists; 12.2% (n = 41) were oral health therapists, and the remaining 2.1% (n = 7) were dental therapists. While the majority (95.2%) agreed that oral cancer screening should be routinely performed, in actual practice around half (51.4%) screened all their patients. Another 12.8% "Very rarely" conducted screening examinations. The probability of routinely conducting an oral cancer screening was explored utilising Logistic Regression Analysis. Four variables remained statistically significant (p oral cancer screening rose with increasing levels of OHPs' confidence in oral cancer-related knowledge (OR = 1.35; 95% CI: 1.09-1.67) and with higher levels of confidence in discussing oral hygiene practices with patients (OR = 1.25; 95% CI: 1.03-1.52). Results also showed that dental specialists were less likely to perform oral cancer screening examinations compared with other OHPs (OR = 0.18; 95% CI: 0.07-0.52) and the likelihood of performing an oral cancer screening decreased when the "patient complained of a problem" (OR = 0.21; 95% CI: 0.10-0.44). Only half the study sample performed oral cancer screening examinations for all of their patients

  10. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling

    International Nuclear Information System (INIS)

    Singhal, Sharad S.; Singh, Sharda P.; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-01-01

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes — higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. - Highlights: • GSTs are the major

  11. Betel nut chewing, oral premalignant lesions, and the oral microbiome.

    Science.gov (United States)

    Hernandez, Brenda Y; Zhu, Xuemei; Goodman, Marc T; Gatewood, Robert; Mendiola, Paul; Quinata, Katrina; Paulino, Yvette C

    2017-01-01

    Oral cancers are attributed to a number of causal agents including tobacco, alcohol, human papillomavirus (HPV), and areca (betel) nut. Although betel nut chewing has been established as an independent cause of oral cancer, the mechanisms of carcinogenesis are poorly understood. An investigation was undertaken to evaluate the influence of betel nut chewing on the oral microbiome and oral premalignant lesions. Study participants were recruited from a dental clinic in Guam. Structured interviews and oral examinations were performed. Oral swabbing and saliva samples were evaluated by 454 pyrosequencing of the V3- V5 region of the 16S rRNA bacterial gene and genotyped for HPV. One hundred twenty-two adults were enrolled including 64 current betel nut chewers, 37 former chewers, and 21 with no history of betel nut use. Oral premalignant lesions, including leukoplakia and submucous fibrosis, were observed in 10 chewers. Within-sample bacterial diversity was significantly lower in long-term (≥10 years) chewers vs. never chewers and in current chewers with oral lesions vs. individuals without lesions. Between-sample bacterial diversity based on Unifrac distances significantly differed by chewing status and oral lesion status. Current chewers had significantly elevated levels of Streptococcus infantis and higher and lower levels of distinct taxa of the Actinomyces and Streptococcus genera. Long-term chewers had reduced levels of Parascardovia and Streptococcus. Chewers with oral lesions had significantly elevated levels of Oribacterium, Actinomyces, and Streptococcus, including Streptococcus anginosus. In multivariate analyses, controlling for smoking, oral HPV, S.anginosus, and S. infantis levels, current betel nut chewing remained the only predictor of oral premalignant lesions. Our study provides evidence that betel nut chewing alters the oral bacterial microbiome including that of chewers who develop oral premalignant lesions. Nonetheless, whether microbial changes

  12. Irradiation mucositis and oral flora

    International Nuclear Information System (INIS)

    Spijkervet, F.K.L.

    1989-01-01

    This study, which is motivated by the substantial morbidity of local signs of mucositis and generalized symptoms that result from mucositis induced by therapeutic irradiation, has the following objectives: To investigate if it is possible to prevent irradiation mucositis via oral flora elimination, and, if it is true that flora plays a role in irradiation mucositis, what fraction of the oral flora may be involved; to evaluate oral Gram-negative bacillary carriage; to investigate the possibility to eradicate Gram-negative bacilli from the oral cavity; to evaluate oral yeast carriage; to investigate the possibility to eradicate yeasts stomatitis and the 'selectivity' of elimination of flora. Two methods are described for monitoring alterations of mucositis of the oral cavity and changes in oral flora. Chlorhexidine has been tested as the commonly used prophylaxis. The effect of chlorhexidine 0.1% rinses on oral flora and mucositis has been studied in a prospective placebo controlled double blind randomized programme. The results of the influence of saliva on the antimicrobial activity of chlorhexidine and the results of selective elimination of oral flora in irradiated patients who have head and neck cancer are reported. Salivary inactivation of the topical antimicrobials used for selective elimination of oral flora has been studied and the results are reported. Finally, the objectives that have been achieved (or not) are delineated. The significance of the results of the study are discussed in terms of published information and further lines of research are suggested. (author). 559 refs.; 29 figs.; 20 tabs

  13. THE EFFECT OF POLYMORPHISM IN GLUTATHIONE S-TRANSFERASES ON THE DEVELOPING SECOND MALIGNANT NEOPLASMS AFTER LEUKEMIA TREATMENT IN CHILDHOOD

    Directory of Open Access Journals (Sweden)

    Janez Jazbec

    2004-12-01

    Full Text Available Background. Survivors of childhood leukemia have an increased risk of developing second malignant neoplasms and specific treatment factors such as alkylating agents, topoisomerase inhibitors and radiation have been associated with their occurrence. Genetic polymorphism in drug-metabolizing enzymes may result in impared detoxification of chemotherapeutics and may lead to increased risk for cancer.Methods. To test if polymorphism in glutathione S-transferases (GST genes is associated with occurrence of secondary malignant neoplasms, we compared GSTM1, GSTT1 and GSTP1 genotypes among 16 patients treated for childhood leukemia in whom second neoplasm occurred and matched the control group.Results. GSTM1 null genotype was found in 44% of patients with second neoplasms and in 50% in control group (p = 0.768, GSTT1 null genotype in 19% of cases and in 29% of controls (p = 0.729 and GSTP1 105 Ile/ile in 50% of cases and 37% of controls (p = 0.537. Differences in distribution of GST genotypes in patients with second neoplasms after childhood leukemia, compared to a matched control group of patients were not statistically significant.Conclusions. In our study we were not able to show relation between GST genotype and occurrence of second neoplasms after the childhood acute leukemia.

  14. Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.

    Science.gov (United States)

    Videen, J S; Haseler, L J; Karpinski, N C; Terkeltaub, R A

    1999-08-01

    The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.

  15. Purification and properties of an O-acetyl-transferase from Escherichia coli that can O-acetylate polysialic acid sequences

    International Nuclear Information System (INIS)

    Higa, H.; Varki, A.

    1986-01-01

    Certain strains of bacteria synthesize an outer polysialic acid (K1) capsule. Some strains of K1 + E.coli are also capable of adding O-acetyl-esters to the exocyclic hydroxyl groups of the sialic acid residues. Both the capsule and the O-acetyl modification have been correlated with differences in antigenicity and pathogenicity. The authors have developed an assay for an O-acetyl-transferase in E.coli that transfers O-[ 3 H]acetyl groups from [ 3 H]acetyl-Coenzyme A to colominic acid (fragments of the polysialic acid capsule). Using this assay, the enzyme was solubilized, and purified ∼ 600-fold using a single affinity chromatography step with Procion Red-A Agarose. The enzyme also binds to Coenzyme A Sepharose, and can be eluted with high salt or Coenzyme A. The partially purified enzyme has a pH optimum of 7.0 - 7.5, is unaffected by divalent cations, is inhibited by high salt concentrations, is inhibited by Coenzyme A (50% inhibition at 100 μM), and shows an apparent Km for colominic acid of 3.7 mM (sialic acid concentration). This enzyme could be involved in the O-acetyl +/- form variation seen in some strains of K1 + E.coli

  16. Differential substrate behaviours of ethylene oxide and propylene oxide towards human glutathione transferase theta hGSTT1-1.

    Science.gov (United States)

    Thier, R; Wiebel, F A; Bolt, H M

    1999-11-01

    The transformation of ethylene oxide (EO), propylene oxide (PO) and 1-butylene oxide (1-BuO) by human glutathione transferase theta (hGSTT1-1) was studied comparatively using 'conjugator' (GSTT1 + individuals) erythrocyte lysates. The relative sequence of velocity of enzymic transformation was PO > EO > 1-BuO. The faster transformation of PO compared to EO was corroborated in studies with human and rat GSTT1-1 (hGSTT1-1 and rGSTT1-1, respectively) expressed by Salmonella typhimurium TA1535. This sequence of reactivities of homologous epoxides towards GSTT1-1 contrasts to the sequence observed in homologous alkyl halides (methyl bromide, MBr; ethyl bromide, EtBr; n-propyl bromide, PrBr) where the relative sequence MeBr > EtBr > PrBr is observed. The higher reactivity towards GSTT1-1 of propylene oxide compared to ethylene oxide is consistent with a higher chemical reactivity. This is corroborated by experimental data of acid-catalysed hydrolysis of a number of aliphatic epoxides, including ethylene oxide and propylene oxide and consistent with semi-empirical molecular orbital modelings.

  17. A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

    Directory of Open Access Journals (Sweden)

    Sahin Erdol MD

    2016-05-01

    Full Text Available Succinyl-CoA:3-oxoacid CoA transferase (SCOT deficiency is an autosomal recessive disorder of ketone body utilization that is clinically characterized with intermittent ketoacidosis crises. We report here the second Turkish case with SCOT deficiency. She experienced 3 ketoacidotic episodes: The first ketoacidotic crisis mimicked diabetic ketoacidosis because of the associated hyperglycemia. Among patients with SCOT deficiency, the blood glucose levels at the first crises were variable, and this case had the highest ever reported blood glucose level. She is a compound heterozygote with 2 novel mutations, c.517A>G (K173E and c.1543A>G (M515V, in exons 5 and 17 of the OXCT1 gene, respectively. In patient’s fibroblasts, SCOT activity was deficient and, by immunoblot analysis, SCOT protein was much reduced. The patient attained normal development and had no permanent ketosis. The accurate diagnosis of SCOT deficiency in this case had a vital impact on the management strategy and outcome.

  18. Fractal binding and dissociation kinetics of lecithin cholesterol acyl transferase (LCAT), a heart-related compound, on biosensor surfaces

    Science.gov (United States)

    Doke, Atul M.; Sadana, Ajit

    2006-05-01

    A fractal analysis is presented for the binding and dissociation of different heart-related compounds in solution to receptors immobilized on biosensor surfaces. The data analyzed include LCAT (lecithin cholesterol acyl transferase) concentrations in solution to egg-white apoA-I rHDL immobilized on a biosensor chip surface.1 Single- and dual- fractal models were employed to fit the data. Values of the binding and the dissociation rate coefficient(s), affinity values, and the fractal dimensions were obtained from the regression analysis provided by Corel Quattro Pro 8.0 (Corel Corporation Limited).2 The binding rate coefficients are quite sensitive to the degree of heterogeneity on the sensor chip surface. Predictive equations are developed for the binding rate coefficient as a function of the degree of heterogeneity present on the sensor chip surface and on the LCAT concentration in solution, and for the affinity as a function of the ratio of fractal dimensions present in the binding and the dissociation phases. The analysis presented provided physical insights into these analyte-receptor reactions occurring on different biosensor surfaces.

  19. Proteomic Profiling of Cytosolic Glutathione Transferases from Three Bivalve Species: Corbicula fluminea, Mytilus galloprovincialis and Anodonta cygnea

    Directory of Open Access Journals (Sweden)

    José Carlos Martins

    2014-01-01

    Full Text Available Suspension-feeding bivalves are considered efficient toxin vectors with a relative insensitivity to toxicants compared to other aquatic organisms. This fact highlights the potential role of detoxification enzymes, such as glutathione transferases (GSTs, in this bivalve resistance. Nevertheless, the GST system has not been extensively described in these organisms. In the present study, cytosolic GSTs isoforms (cGST were surveyed in three bivalves with different habitats and life strategies: Corbicula fluminea, Anodonta cygnea and Mytilus galloprovincialis. GSTs were purified by glutathione-agarose affinity chromatography, and the collection of expressed cGST classes of each bivalve were identified using a proteomic approach. All the purified extracts were also characterized kinetically. Results reveal variations in cGST subunits collection (diversity and properties between the three tested bivalves. Using proteomics, four pi-class and two sigma-class GST subunits were identified in M. galloprovincialis. C. fluminea also yielded four pi-class and one sigma-class GST subunits. For A. cygnea, two mu-class and one pi-class GST subunits were identified, these being the first record of GSTs from these freshwater mussels. The affinity purified extracts also show differences regarding enzymatic behavior among species. The variations found in cGST collection and kinetics might justify diverse selective advantages for each bivalve organism.

  20. In silico genome-wide identification and characterization of the glutathione S-transferase gene family in Vigna radiata.

    Science.gov (United States)

    Vaish, Swati; Awasthi, Praveen; Tiwari, Siddharth; Tiwari, Shailesh Kumar; Gupta, Divya; Basantani, Mahesh Kumar

    2018-05-01

    Plant glutathione S-transferases (GSTs) are integral to normal plant metabolism and biotic and abiotic stress tolerance. The GST gene family has been characterized in diverse plant species using molecular biology and bioinformatics approaches. In the current study, in silico analysis identified 44 GSTs in Vigna radiata. Of the total 44 GSTs identified, chromosomal locations of 31 GSTs were confirmed. The pI value of GST proteins ranged from 5.10 to 9.40. The predicted molecular weights ranged from 13.12 to 50 kDa. Subcellular localization analysis revealed that all GSTs were predominantly localized in the cytoplasm. The active site amino acids were confirmed to be serine in tau, phi, theta, zeta, and TCHQD; cysteine in lambda, DHAR, and omega; and tyrosine in EF1G. The gene architecture conformed to the two-exon/one-intron and three-exon/two-intron organization in the case of tau and phi classes, respectively. MEME analysis identified 10 significantly conserved motifs with the width of 8-50 amino acids. The motifs identified were either specific to a specific GST class or were shared by multiple GST classes. The results of the current study will be of potential importance in the characterization of the GST gene family in V. radiata, an economically important leguminous crop.

  1. Crystal Structure of Saccharomyces cerevisiae ECM4, a Xi-Class Glutathione Transferase that Reacts with Glutathionyl-(hydro)quinones

    Science.gov (United States)

    Schwartz, Mathieu; Didierjean, Claude; Hecker, Arnaud; Girardet, Jean-Michel; Morel-Rouhier, Mélanie; Gelhaye, Eric; Favier, Frédérique

    2016-01-01

    Glutathionyl-hydroquinone reductases (GHRs) belong to the recently characterized Xi-class of glutathione transferases (GSTXs) according to unique structural properties and are present in all but animal kingdoms. The GHR ScECM4 from the yeast Saccharomyces cerevisiae has been studied since 1997 when it was found to be potentially involved in cell-wall biosynthesis. Up to now and in spite of biological studies made on this enzyme, its physiological role remains challenging. The work here reports its crystallographic study. In addition to exhibiting the general GSTX structural features, ScECM4 shows extensions including a huge loop which contributes to the quaternary assembly. These structural extensions are probably specific to Saccharomycetaceae. Soaking of ScECM4 crystals with GS-menadione results in a structure where glutathione forms a mixed disulfide bond with the cysteine 46. Solution studies confirm that ScECM4 has reductase activity for GS-menadione in presence of glutathione. Moreover, the high resolution structures allowed us to propose new roles of conserved residues of the active site to assist the cysteine 46 during the catalytic act. PMID:27736955

  2. Crystal Structure of Saccharomyces cerevisiae ECM4, a Xi-Class Glutathione Transferase that Reacts with Glutathionyl-(hydroquinones.

    Directory of Open Access Journals (Sweden)

    Mathieu Schwartz

    Full Text Available Glutathionyl-hydroquinone reductases (GHRs belong to the recently characterized Xi-class of glutathione transferases (GSTXs according to unique structural properties and are present in all but animal kingdoms. The GHR ScECM4 from the yeast Saccharomyces cerevisiae has been studied since 1997 when it was found to be potentially involved in cell-wall biosynthesis. Up to now and in spite of biological studies made on this enzyme, its physiological role remains challenging. The work here reports its crystallographic study. In addition to exhibiting the general GSTX structural features, ScECM4 shows extensions including a huge loop which contributes to the quaternary assembly. These structural extensions are probably specific to Saccharomycetaceae. Soaking of ScECM4 crystals with GS-menadione results in a structure where glutathione forms a mixed disulfide bond with the cysteine 46. Solution studies confirm that ScECM4 has reductase activity for GS-menadione in presence of glutathione. Moreover, the high resolution structures allowed us to propose new roles of conserved residues of the active site to assist the cysteine 46 during the catalytic act.

  3. Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids

    International Nuclear Information System (INIS)

    Angsten, Gertrud; Valind, Sven; Takalo, Reijo; Neu, Henrik; Meurling, Staffan; Langstroem, Bengt

    2005-01-01

    Methods: Anesthetized pigs were studied with [ 11 C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [ 11 C]-FAs from blood was measured together with the relative distribution of [ 11 C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [ 11 C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [ 11 C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs

  4. Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [{sup 11}C]-labeled fatty acids

    Energy Technology Data Exchange (ETDEWEB)

    Angsten, Gertrud [Department of Pediatric Surgery, University Children' s Hospital, S-751 85 Uppsala (Sweden)]. E-mail: gertrud.angsten@surgsci.uu.se; Valind, Sven [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Clinical Physiology, University Hospital, S-751 85 Uppsala (Sweden); Takalo, Reijo [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Clinical Physiology, University Hospital, S-751 85 Uppsala (Sweden); Neu, Henrik [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Organic Chemistry, Uppsala University, S-751 24 Uppsala (Sweden); Meurling, Staffan [Department of Pediatric Surgery, University Children' s Hospital, S-751 85 Uppsala (Sweden); Langstroem, Bengt [Uppsala University PET Centre, Uppsala University, S-751 05 Uppsala (Sweden); Department of Organic Chemistry, Uppsala University, S-751 24 Uppsala (Sweden)

    2005-07-01

    Methods: Anesthetized pigs were studied with [{sup 11}C]-labeled fatty acids (FAs) with carbon chain length ranging from 8 to 16 carbon atoms, during control conditions and during inhibition of carnitine-palmitoyl transferase I (CPT I) with oxfenicine. The myocardial uptake of [{sup 11}C]-FAs from blood was measured together with the relative distribution of [{sup 11}C]-acyl-CoA between rapid mitochondrial oxidation and incorporation into slow turnover lipid pools in the heart. Results: During baseline conditions, the fractional oxidative utilization of palmitate was almost as high as that of carnitine-independent short-chain FAs, unless the carnitine shuttle was inhibited by high levels of lactate. Inhibition of CPT I almost completely blocked the oxidative pathway for palmitic acid and reduced the fractional oxidative utilization, while the rate of oxidative metabolism of acyl-CoA was unaffected. Conclusions: [{sup 11}C]-Labeled FAs allow rapid oxidation to be well separated from esterification into slow turnover lipid pools in the heart of anaesthetized pigs. The fractional oxidative utilization of [{sup 11}C]-palmitate serves well to characterize, in vivo, the carnitine-dependent transfer of long-chain FAs.

  5. Mechanistic insights into EgGST1, a Mu class glutathione S-transferase from the cestode parasite Echinococcus granulosus.

    Science.gov (United States)

    Arbildi, Paula; Turell, Lucía; López, Verónica; Alvarez, Beatriz; Fernández, Verónica

    2017-11-01

    Glutathione transferases (GSTs) comprise a major detoxification system in helminth parasites, displaying both catalytic and non-catalytic activities. The kinetic mechanism of these enzymes is complex and depends on the isoenzyme which is being analyzed. Here, we characterized the kinetic mechanism of rEgGST1, a recombinant form of a cytosolic GST from Echinococcus granulosus (EgGST1), which is related to the Mu-class of mammalian enzymes, using the canonical substrates glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB). Initial rate and product inhibition studies were consistent with a steady-state random sequential mechanism, where both substrates are bound to the enzyme before the products are released. Kinetic constants were also determined (pH 6.5 and 30 °C). Moreover, rEgGST1 lowered the pK a of GSH from 8.71 ± 0.07 to 6.77 ± 0.08, and enzyme-bound GSH reacted with CDNB 1 × 10 5 times faster than free GSH at pH 7.4. Finally, the dissociation of the enzyme-GSH complex was studied by means of intrinsic fluorescence, as well as that of the complex with the anthelminth drug mebendazole. This is the first report on mechanistic issues related to a helminth parasitic GST. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Human T cell recognition of the blood stage antigen Plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT in acute malaria

    Directory of Open Access Journals (Sweden)

    Woodberry Tonia

    2009-06-01

    Full Text Available Abstract Background The Plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT can protect mice against Plasmodium yoelii pRBC challenge in a T cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. It is not known whether natural exposure to Plasmodium falciparum stimulates HGXPRT T cell reactivity in humans. Methods PBMC and plasma collected from malaria-exposed Indonesians during infection and 7–28 days after anti-malarial therapy, were assessed for HGXPRT recognition using CFSE proliferation, IFNγ ELISPOT assay and ELISA. Results HGXPRT-specific T cell proliferation was found in 44% of patients during acute infection; in 80% of responders both CD4+ and CD8+ T cell subsets proliferated. Antigen-specific T cell proliferation was largely lost within 28 days of parasite clearance. HGXPRT-specific IFN-γ production was more frequent 28 days after treatment than during acute infection. HGXPRT-specific plasma IgG was undetectable even in individuals exposed to malaria for at least two years. Conclusion The prevalence of acute proliferative and convalescent IFNγ responses to HGXPRT demonstrates cellular immunogenicity in humans. Further studies to determine minimal HGXPRT epitopes, the specificity of responses for Plasmodia and associations with protection are required. Frequent and robust T cell proliferation, high sequence conservation among Plasmodium species and absent IgG responses distinguish HGXPRT from other malaria antigens.

  7. γ-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke.

    Science.gov (United States)

    Tu, Wen-Jun; Liu, Qiang; Cao, Jian-Lei; Zhao, Sheng-Jie; Zeng, Xian-Wei; Deng, Ai-Jun

    2017-10-01

    The aim of the study was to evaluate the association of the measurement of serum γ-glutamyl transferase (GGT) concentrations at admission with 1-year all-cause or cardiovascular disease (CVD) mortality in patients with acute ischemic stroke. This prospective, multicenter cohort study was conducted in 4 stroke centers in China. Baseline GGT measurements were tested. The relationship of GGT to the risk of death from all-cause or CVD was examined among 1-year follow-up patients. We recorded results from 5912 patients with stroke. In those patients, 51.0% were men, and the median age was 61 years. In both men and women, high GGT was significantly associated with total mortality from all-cause or CVD ( P mortality from all-cause and CVD, respectively. With an area under the curve of 0.69 (95% confidence interval, 0.66-0.73), GGT showed a significantly greater discriminatory ability to predict all-cause mortality as compared with others factors. GGT improved the National Institutes of Health Stroke Scale score (area under the curve of the combined model, 0.75 [95% confidence interval, 0.73-0.78]; P mortality in patients with ischemic stroke. © 2017 American Heart Association, Inc.

  8. Glutathione S-transferase of brown planthoppers (Nilaparvata lugens is essential for their adaptation to gramine-containing host plants.

    Directory of Open Access Journals (Sweden)

    Xiao-Qin Sun

    Full Text Available Plants have evolved complex processes to ward off attacks by insects. In parallel, insects have evolved mechanisms to thwart these plant defenses. To gain insight into mechanisms that mediate this arms race between plants and herbivorous insects, we investigated the interactions between gramine, a toxin synthesized by plants of the family Gramineae, and glutathione S transferase (GST, an enzyme found in insects that is known to detoxify xenobiotics. Here, we demonstrate that rice (Oryza sativa, a hydrophytic plant, also produces gramine and that rice resistance to brown planthoppers (Nilaparvata lugens, BPHs is highly associated with in planta gramine content. We also show that gramine is a toxicant that causes BPH mortality in vivo and that knockdown of BPH GST gene nlgst1-1 results in increased sensitivity to diets containing gramine. These results suggest that the knockdown of key detoxification genes in sap-sucking insects may provide an avenue for increasing their sensitivity to natural plant-associated defense mechanisms.

  9. Design and production of various fusion proteins of the nicotinamide/nicotinate mononucleotide adenilil transferase (NMNAT of Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Carlos Alfonso Nieto Clavijo

    2017-09-01

    Full Text Available Recombinant proteins have become useful tools in biochemistry research. During their production, however, inclusion bodies (IB appear, on the one hand, due to the high expression rate from the recombinant plasmids, which have high efficiency promoters, and, on the other hand, intrinsic characteristics of the expressed protein. Furhtermore, the nicotinamide/nicotinate mononucleotide adenilyl transferase (NMNAT is a central protein in NAD(H+ biosynthesis, an essential cofactor in cell metabolism, and in protozoon parasite has been studied. To study the NMNAT protein of these parasites, their recombinant version in E. coli has been expressed, getting a great quantity of IB as a by-product. To increase the solubility of the protein, the coding sequence of the NMNAT enzyme of Plasmodium falciparum was cloned in different expression plasmids which were subsequently transformed into E. coli BL21(DE3 expression strain. The solubility of the recombinant proteins was assessed and the one with the highest presence in the soluble fraction was subsequently purified and its enzyme activity was determined. The recombinant protein with a MBP (maltose-binding protein tag showed an increased solubility and purity.

  10. Purification and properties of the glutathione S-transferases from the anoxia-tolerant turtle, Trachemys scripta elegans.

    Science.gov (United States)

    Willmore, William G; Storey, Kenneth B

    2005-07-01

    Glutathione S-transferases (GSTs) play critical roles in detoxification, response to oxidative stress, regeneration of S-thiolated proteins, and catalysis of reactions in nondetoxification metabolic pathways. Liver GSTs were purified from the anoxia-tolerant turtle, Trachemys scripta elegans. Purification separated a homodimeric (subunit relative molecular mass =34 kDa) and a heterodimeric (subunit relative molecular mass = 32.6 and 36.8 kDa) form of GST. The enzymes were purified 23-69-fold and 156-174-fold for homodimeric and heterodimeric GSTs, respectively. Kinetic data gathered using a variety of substrates and inhibitors suggested that both homodimeric and heterodimeric GSTs were of the alpha class although they showed significant differences in substrate affinities and responses to inhibitors. For example, homodimeric GST showed activity with known alpha class substrates, cumene hydroperoxide and p-nitrobenzylchloride, whereas heterodimeric GST showed no activity with cumene hydroperoxide. The specific activity of liver GSTs with chlorodinitrobenzene (CDNB) as the substrate was reduced by 2.6- and 8.7-fold for homodimeric and heterodimeric GSTs isolated from liver of anoxic turtles as compared with aerobic controls, suggesting an anoxia-responsive stable modification of the protein that may alter its function during natural anaerobiosis.

  11. Designing Ligands for Leishmania, Plasmodium, and Aspergillus N-Myristoyl Transferase with Specificity and Anti-Target-Safe Virtual Libraries.

    Science.gov (United States)

    Garcia-Sosa, Alfonso T

    2018-01-01

    Leishmaniasis, malaria, and fungal diseases are burdens on individuals and populations and can present severe complications. Easily accessible chemical treatments for these diseases are increasingly sought-after. Targeting the parasite N-myristoyl transferase while avoiding the human enzyme and other anti-targets may allow the prospect of compounds with pan-activity against these diseases, which would simplify treatments and costs. Developing chemical libraries, both virtual and physical, that have been filtered and flagged early on in the drug discovery process (before virtual screening) could reduce attrition rates of compounds being developed and failing late in development stages due to problems of side-effects or toxicity. Chemical libraries have been screened against the anti-targets pregnane-X-receptor, sulfotransferase, cytochrome P450 2a6, 2c9, and 3a4 with three different docking programs. Statistically significant differences are observed in their interactions with these enzymes as compared to small molecule drugs and bioactive non-drug datasets. A series of compounds are proposed with the best predicted profiles for inhibition of all parasite targets while sparing the human form and anti-targets. Some of the topranked compounds have confirmed experimental activity against Leishmania, and highlighted are those compounds with best properties for further development. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron Retention and O-GlcNAc Homeostasis

    Directory of Open Access Journals (Sweden)

    Sung-Kyun Park

    2017-08-01

    Full Text Available Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc transferase (OGT and O-GlcNAcase (OGA add and remove O-GlcNAc, but the mechanisms regulating their expression remain unclear. Here, we demonstrate that retention of the fourth intron of OGT is regulated in response to O-GlcNAc levels. We further define a conserved intronic splicing silencer (ISS that is necessary for OGT intron retention. Deletion of the ISS in colon cancer cells leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant increases in OGA protein. However, the ISS-deleted cells are hypersensitive to OGA inhibition in culture and in soft agar. Moreover, growth of xenograft tumors from ISS-deleted cells is compromised in mice treated with an OGA inhibitor. Thus, ISS-mediated regulation of OGT intron retention is a key component in OGT expression and maintaining O-GlcNAc homeostasis.

  13. Volatile Gas Production by Methyl Halide Transferase: An In Situ Reporter Of Microbial Gene Expression In Soil.

    Science.gov (United States)

    Cheng, Hsiao-Ying; Masiello, Caroline A; Bennett, George N; Silberg, Jonathan J

    2016-08-16

    Traditional visual reporters of gene expression have only very limited use in soils because their outputs are challenging to detect through the soil matrix. This severely restricts our ability to study time-dependent microbial gene expression in one of the Earth's largest, most complex habitats. Here we describe an approach to report on dynamic gene expression within a microbial population in a soil under natural water levels (at and below water holding capacity) via production of methyl halides using a methyl halide transferase. As a proof-of-concept application, we couple the expression of this gas reporter to the conjugative transfer of a bacterial plasmid in a soil matrix and show that gas released from the matrix displays a strong correlation with the number of transconjugant bacteria that formed. Gas reporting of gene expression will make possible dynamic studies of natural and engineered microbes within many hard-to-image environmental matrices (soils, sediments, sludge, and biomass) at sample scales exceeding those used for traditional visual reporting.

  14. Association of N-acetyltransferase-2 and glutathione S-transferase polymorphisms with idiopathic male infertility in Vietnam male subjects.

    Science.gov (United States)

    Trang, Nguyen Thi; Huyen, Vu Thi; Tuan, Nguyen Thanh; Phan, Tran Duc

    2018-04-25

    N-acetyltransferase-2 (NAT2) and Glutathione S-transferases (GSTs) are phase-II xenobiotic metabolizing enzymes participating in detoxification of toxic arylamines, aromatic amines, hydrazines and reactive oxygen species (ROS), which are produced under oxidative and electrophile stresses. The purpose of this research was to investigate whether two common single-nucleotide polymorphisms (SNP) of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) associated with susceptibility to idiopathic male infertility. A total 300 DNA samples (150 infertile patients and 150 healthy control) were genotyped for the polymorphisms by ARMS - PCR. We revealed a significant association between the NAT2 variant genotypes (CT + TT (rs1799929), (OR: 3.74; p male infertility in subjects from Vietnam. This pilot study is the first (as far as we know) to reveal that polymorphisms of NAT2 (rs1799929, rs1799930) and GSTP1 (rs1138272, rs1695) are some novel genetic markers for susceptibility to idiopathic male infertility. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Effect of Arsenic and Chromium on the Serum Amino-Transferases Activity in Indian Major Carp, Labeo rohita

    Directory of Open Access Journals (Sweden)

    Anjaneyulu Yerramilli

    2007-09-01

    Full Text Available Arsenic and hexavalent chromium toxicity results from their ability to interact with sulfahydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Alanine aminotransferase (ALT; E.C: 2.6.1.2 and Aspartate amino transferase (AST; EC 2.6.1.1 play a crucial role in transamination reactions and can be used as potential biomarkers to indicate hepatotoxicity and cellular damage. While histopathological studies in liver tissue require more time and expertise, simple and reliable biochemical analysis of ALT and AST can be used for a rapid assessment of tissue and cellular damage within 96 h. The main objective of this study was to determine the acute effects of arsenic and hexavalent chromium on the activity of ALT and AST in the Indian major carp, Labeo rohita for 24 h and 96 h. Significant increase in the activity of ALT (P < 0.01 from controls in arsenic exposed fish indicates serious hepatic damage and distress condition to the fish. However, no such significant changes were observed in chromium-exposed fish suggesting that arsenic is more toxic to the fish. These findings indicate that ALT and AST are candidate biomarkers for arsenic-induced hepatotoxicity in Labeo rohita.

  16. An acetylation site in lectin domain modulates the biological activity of polypeptide GalNAc-transferase-2

    DEFF Research Database (Denmark)

    Zlocowski, Natacha; Lorenz, Virginia; Bennett, Eric Paul

    2013-01-01

    Abstract Polypeptide GalNAc-transferases (ppGalNAc-Ts) are a family of enzymes that catalyze the initiation of mucin-type O-glycosylation. All ppGalNAc-T family members contain a common (QXW)3 motif which is present in R-type lectin group. Acetylation site K521 is part of the QKW motif of ß......-trefoil in the lectin domain of ppGalNAc-T2. We used a combination of acetylation and site-directed mutagenesis approaches to examine the functional role of K521 in ppGalNAc-T2. Binding assays of non-acetylated and acetylated forms of the mutant ppGalNAc-T2K521Q to various naked and aGalNAc-glycosylated mucin peptides...... indicated that degree of interaction of lectin domain with aGalNAc depends on the peptide sequence of mucin. Studies of inhibitory effect of various carbohydrates on interactions of ppGalNAc-T2 with MUC1aGalNAc indicate that point K521Q mutation enhance the carbohydrate specificity of lectin domain for aGalNAc...

  17. Evaluation of the precision-cut liver and lung slice systems for the study of induction of CYP1, epoxide hydrolase and glutathione S-transferase activities.

    Science.gov (United States)

    Pushparajah, Daphnee S; Umachandran, Meera; Plant, Kathryn E; Plant, Nick; Ioannides, Costas

    2007-02-28

    The principal objective was to ascertain whether precision-cut tissue slices can be used to evaluate the potential of chemicals to induce CYP1, epoxide hydrolase and glutathione S-transferase activities, all being important enzymes involved in the metabolism of polycyclic aromatic hydrocarbons. Precision-cut rat liver and lung slices were incubated with a range of benzo[a]pyrene concentrations for various time periods. A rise in the O-deethylation of ethoxyresorufin was seen in both liver and lung slices exposed to benzo[a]pyrene, which was accompanied by increased CYP1A apoprotein levels. Pulmonary CYP1B1 apoprotein levels and hepatic mRNA levels were similarly enhanced. Elevated epoxide hydrolase and glutathione S-transferase activities were also observed in liver slices following incubation for 24h; similarly, a rise in apoprotein levels of both enzymes was evident, peak levels occurring at the same time point. When mRNA levels were monitored, a rise in the levels of both enzymes was seen as early as 4h after incubation, but maximum levels were attained at 24 h. In lung slices, induction of epoxide hydrolase by benzo[a]pyrene was observed after a 24-h incubation, and at a concentration of 1 microM; a rise in apoprotein levels was seen at this time point. Glutathione S-transferase activity was not inducible in lung slices by benzo[a]pyrene but a modest increase was observed in hepatic slices. Collectively, these studies confirmed CYP1A induction in rat liver slices and established that CYP1B1 expression, and epoxide hydrolase and glutathione S-transferase activities are inducible in precision-cut tissue slices.

  18. Purification, molecular cloning and heterologous expression of a glutathione S-transferase involved in insecticide resistance from the rice brown planthopper, Nilaparvata lugens.

    OpenAIRE

    Vontas, John G; Small, Graham J; Nikou, Dimitra C; Ranson, Hilary; Hemingway, Janet

    2002-01-01

    A novel glutathione S-transferase (GST)-based pyrethroid resistance mechanism was recently identified in Nilaparvata lugens [Vontas, Small and Hemingway (2001) Biochem. J. 357, 65-72]. To determine the nature of GSTs involved in conferring this resistance, the GSTs from resistant and susceptible strains of N. lugens were partially purified by anion exchange and affinity chromatography. The majority of peroxidase activity, previously correlated with resistance, was confined to the fraction tha...

  19. An ethylene-responsive enhancer element is involved in the senescence-related expression of the carnation glutathione-S-transferase (GST1) gene.

    OpenAIRE

    Itzhaki, H; Maxson, J M; Woodson, W R

    1994-01-01

    The increased production of ethylene during carnation petal senescence regulates the transcription of the GST1 gene encoding a subunit of glutathione-S-transferase. We have investigated the molecular basis for this ethylene-responsive transcription by examining the cis elements and trans-acting factors involved in the expression of the GST1 gene. Transient expression assays following delivery of GST1 5' flanking DNA fused to a beta-glucuronidase receptor gene were used to functionally define ...

  20. [New oral anticoagulant drugs].

    Science.gov (United States)

    Berkovits, Alejandro; Aizman, Andrés; Zúñiga, Pamela; Pereira, Jaime; Mezzano, Diego

    2011-10-01

    Thromboembolic disease (TED) is the leading cause of morbidity and mortality worldwide. The hallmark of oral long-term anticoagulant therapy has been the use of vitamin K antagonists, whose anticoagulant effect is exerted inhibiting vitamin K epoxide reductase. Warfarin and acenocoumarol are the most commonly used. In the last five years several new drugs for long term anticoagulation have been developed, which can inhibit single clotting factors with the purpose of improving drug therapeutic range and, ideally, minimizing bleeding risks. This review addresses the state of the art on the clinical use of inhibitors of activated factor X and thrombin.

  1. Two pear glutathione S-transferases genes are regulated during fruit development and involved in response to salicylic acid, auxin, and glucose signaling.

    Directory of Open Access Journals (Sweden)

    Hai-Yan Shi

    Full Text Available Two genes encoding putative glutathione S-transferase proteins were isolated from pear (Pyrus pyrifolia and designated PpGST1 and PpGST2. The deduced PpGST1 and PpGST2 proteins contain conserved Glutathione S-transferase N-terminal domain (GST_N and Glutathione S-transferase, C-terminal domain (GST_C. Using PCR amplification technique, the genomic clones corresponding to PpGST1 and PpGST2 were isolated and shown to contain two introns and a singal intron respectively with typical GT/AG boundaries defining the splice junctions. Phylogenetic analysis clearly demonstrated that PpGST1 belonged to Phi class of GST superfamilies and had high homology with apple MdGST, while PpGST2 was classified into the Tau class of GST superfamilies. The expression of PpGST1 and PpGST2 genes was developmentally regulated in fruit. Further study demonstrated that PpGST1 and PpGST2 expression was remarkably induced by glucose, salicylic acid (SA and indole-3-aceticacid (IAA treatments in pear fruit, and in diseased fruit. These data suggested that PpGST1 and PpGST2 might be involved in response to sugar, SA, and IAA signaling during fruit development of pear.

  2. Oral complications in cancer patients

    International Nuclear Information System (INIS)

    Carl, W.

    1983-01-01

    Ionizing radiation used in treating the head and neck area produces oral side effects such as mucositis, salivary changes, trismus and radiation caries. Sequelae of cancer chemotherapy often include oral stomatitis, myelosuppression and immunosuppression. Infections of dental origin in compromised patients are potentially lethal. Specific programs to eliminate dental pathology before radiation and chemotherapy, and to maintain oral hygiene during and after therapy, will minimize these complications

  3. Drug Reactions in Oral Mucosa

    Directory of Open Access Journals (Sweden)

    Emine Derviş

    2012-12-01

    Full Text Available Both immunologic and nonimmunologic drug reactions can be seen in oral mucosa. Since considerable number of these reactions heals spontaneously without being noticed by the patients, exact frequency of the lesions is unknown. Most common lesions are xerostomia, taste disorders, mucosal ulcerations and edema. In this article, oral lesions resulting from drug intake similar to those from oral lesions of local and systemic diseases, and diagnostic problems caused by these similarities, have been reviewed.

  4. Oral cancer: A multicenter study.

    Science.gov (United States)

    Dhanuthai, K; Rojanawatsirivej, S; Thosaporn, W; Kintarak, S; Subarnbhesaj, A; Darling, M; Kryshtalskyj, E; Chiang, C-P; Shin, H-I; Choi, S-Y; Lee, S-S; Aminishakib, P

    2018-01-01

    To determine the prevalence and clinicopathologic features of the oral cancer patients. Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as between Asian and non-Asian oral cancer patients.

  5. Pathogenesis of oral FIV infection.

    Directory of Open Access Journals (Sweden)

    Craig Miller

    Full Text Available Feline immunodeficiency virus (FIV is the feline analogue of human immunodeficiency virus (HIV and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii FIV viral load in oral lymphoid tissues (tonsil, lymph nodes is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue; (iv salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis

  6. EFEK POLIMORFISME GENA GSTP-1 TERHADAP AKTIVITAS GLUTATION S-TRANSFERASE (GST PADA INDIVIDU TERPAPAR LOGAM BERAT TIMBAL (Effect of GSTP-1 Gene Polymorphismson Glutation S- Transferase (GST Activity in Heavy Metals Lead-Exposed Individual

    Directory of Open Access Journals (Sweden)

    Hernayanti Hernayanti

    2015-11-01

    Full Text Available ABSTRAK Gena GSTP-1 merupakan penghasil enzim glutation S- transferase (GST, yang berfungsi dalam proses detoksifikasi senyawa toksik di hati. Faktor keberadaan polimorfisme gena GSTP-1 akan menyebabkan penurunan ekspresi GST, sehingga proses detoksifikasi terhadap senyawa toksik akan terhambat. Kerentanan terhadap paparan senyawa toksik pada manusia akan meningkat apabila dijumpai polimorfisme gena. Salah satu senyawa toksik yang dapat menghambat aktivitas GST adalah timbal (Pb, terutama dalam bentuk tetra ethyl lead (TEL. Tujuan penelitian adalah untuk mengetahui pengaruh polimorfisme gena GSTP-1 terhadap aktivitas GST pada individu terpapar Pb, yang diwakili pekerja bengkel mobil. Faktor keberadaan polimorfisme gena individu ditentukan dengan metode PCR-RFLP dan enzim restriksi BsmA1. Parameter yang diukur adalah kadar Pb dan aktivitas GST. Analisis molekuler gena GSTP-1 dilakukan secara deskriptif. Data kadar Pb dan aktivitas GST dianalisis dengan uji t independent. Hasil analisis gena GSTP-1 dari 40 orang subyek kasus setelah dilakukan digesti dengan enzim BsmA1, ditemukan sebanyak 10 orang individu dengan polimorfisme Ile105Val gena GSTP 1 atau sekitar 25% dengan genotip Ile-Val, sedangkan 30 orang atau 75% ditemukan tanpa polimorfisme dengan genotip Ile-Ile. Pita DNA individu dengan polimorfisme terpotong menjadi 3 fragmen sepanjang 176, 91 dan 85 pp (mutan heterozygot, sedangkan tanpa polimorfisme terletak pada 176 bp. Subyek kasus dengan polimorfisme gena GSTP-1 memiliki kadar Pb lebih tinggi dan aktivitas GST lebih rendah dibandingkan individu non polimorfisme. Telah terbukti bahwa polimorfisme gena GSTP-1 menyebabkan penurunan ekspresi enzim GST. Pada individu terpapar Pb dengan polimorfisme gena GSTP-1 memiliki aktivitas GST lebih rendah dibandingkan individu tanpa polimorfisme. ABSTRACT GSTP-1 gene regulates the expression of gluthation S-transferase enzyme, which role in detoxification of toxicant on liver. If the polymorphisms

  7. Oral yeast colonization throughout pregnancy.

    Science.gov (United States)

    Rio, R; Simões-Silva, L; Garro, S; Silva, M-J; Azevedo, Á; Sampaio-Maia, B

    2017-03-01

    Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment.

  8. Association between Oral Anticoagulation Knowledge ...

    African Journals Online (AJOL)

    Association between Oral Anticoagulation Knowledge, Anticoagulation Control, and Demographic Characteristics of Patients Attending an Anticoagulation Clinic in Saudi Arabia: A Cross-Sectional Prospective Evaluation.

  9. ORAL ALLERGY SYNDROME

    Directory of Open Access Journals (Sweden)

    A. V. Sergeev

    2011-01-01

    Full Text Available Abstract. Oral allergy syndrome (OAS is defined as a set of clinical manifestations caused by IgE-mediated allergic  reactions  that  occur  at  oral  and  pharyngeal  mucosae  in  the  patients  with  pollen  sensitization  after ingestion of certain fruits, vegetables, nuts and spices. OAS arises from cross-reactivity between specific pollen and food allergens, due to similarity of a configuration and amino acid sequence of allergenic molecules. OAS is considered as class II food allergy, being caused by thermo- and chemolabile allergens, and it is rarely combined with generalized manifestations of food allergy. Prevalence and spectrum of the causal allergens depend on a kind of pollen sensitization. In Moscow region, as well as in Northern Europe, allergic sensitization most commonly occurs to the pollen of leaf trees, whereas OAS is mostly connected with ingestion of fruits from Rosaceae family and nuts. Since last years, a newly developed technique of component-resolved molecular diagnosis (CR diagnostics allows of more precise detection of OAS-causing allergen molecules. These data are of extreme importance for administration of adequate nutritional therapy and prediction of SIT efficiency. (Med. Immunol., 2011, vol. 13, N 1, pp 17-28

  10. Role of oral microbiome on oral cancers, a review.

    Science.gov (United States)

    Gholizadeh, Pourya; Eslami, Hosein; Yousefi, Mehdi; Asgharzadeh, Mohammad; Aghazadeh, Mohammad; Kafil, Hossein Samadi

    2016-12-01

    The oral cavity is inhibited by many of the bacterial species. Some of them have a key role in the development of oral disease. Interrelationships between oral microbiome and systemic conditions such as head-and-neck cancer have become increasingly appreciated in recent years. Emerging evidence also suggests a link between periodontal disease and oral cancer, and the explanation being that chronic inflammation could be a major factor in both diseases. Squamous cell carcinoma is that the most frequently occurring malignancy of the oral cavity and adjacent sites, representing over 90% of all cancers. The incidence of oral cancer is increasing, significantly among young people and women. Worldwide there are 350,000-400,000 new cases diagnosed every year. Bacteria, viruses, and fungi are strongly implicated as etiological factors in certain cancers. In this review we will discuss the association between the development of oral cancer in potentially malignant oral lesions with chronic periodontitis, chronic Porphyromonas gingivalis, Fusobacterium nucleatum, candida, other microbes and described mechanisms which may be involved in these carcinoma. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  11. Oral Insulin – Fact or Fiction? - Possibilities of Achieving Oral ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 5. Oral Insulin – Fact or Fiction? - Possibilities of Achieving Oral Delivery of Insulin. K Gowthamarajan Giriraj T Kulkarni. General Article Volume 8 Issue 5 May 2003 pp 38-46 ...

  12. Can the oral microflora affect oral ulcerative mucositis?

    NARCIS (Netherlands)

    Laheij, A.M.G.A.; de Soet, J.J.

    2014-01-01

    Purpose of review: Oral mucositis is one of the most prevalent toxicities after hematopoietic stem cell transplantation. Mucositis is initiated by the chemotherapy or radiotherapy preceding the transplantation. It is commonly accepted that microorganisms play a role in the process of oral mucositis.

  13. Assessing Oral Hygiene in Hospitalized Older Veterans.

    Science.gov (United States)

    Jennings, Andrea

    2015-01-01

    Poor oral health for all older adults can result in higher risk for heart disease, stroke, diabetes, and oral cancer. Findings from this study indicated older veterans needed to improve their oral hygiene habits but barriers to oral hygiene performance prevented them from receiving and performing oral hygiene measures.

  14. Differential activation of diverse glutathione transferases of Clonorchis sinensis in response to the host bile and oxidative stressors.

    Directory of Open Access Journals (Sweden)

    Young-An Bae

    Full Text Available BACKGROUND: Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma. Approximately 35 million people are infected and 600 million people are at risk of infections worldwide. C. sinensis excretory-secretory products (ESP constitute the first-line effector system affecting the host-parasite interrelationship by interacting with bile fluids and ductal epithelium. However, the secretory behavior of C. sinensis in an environment close to natural host conditions is unclear. C. sinensis differs from Fasciola hepatica in migration to, and maturation in, the hepatic bile duct, implying that protein profile of the ESP of these two trematodes might be different from each other. METHODOLOGY/PRINCIPAL FINDINGS: We conducted systemic approaches to analyze the C. sinensis ESP proteome and the biological reactivity of C. sinensis glutathione transferases (GSTs, such as global expression patterns and induction profiles under oxidative stress and host bile. When we observed ex host excretion behavior of C. sinensis in the presence of 10% host bile, the global proteome pattern was not significantly altered, but the amount of secretory proteins was increased by approximately 3.5-fold. Bioactive molecules secreted by C. sinensis revealed universal/unique features in relation to its intraluminal hydrophobic residing niche. A total of 38 protein spots identified abundantly included enzymes involved in glucose metabolism (11 spots, 28.9% and diverse-classes of glutathione transferases (GSTs; 10 spots, 26.3%. Cathepsin L/F (four spots, 10.5% and transporter molecules (three spots, 7.9% were also recognized. The universal secretory proteins found in other parasites, such as several enzymes involved in glucose metabolism and oxygen transporters, were commonly detected. C. sinensis secreted less cysteine proteases and fatty acid binding proteins compared to other tissue-invading or

  15. Differential Activation of Diverse Glutathione Transferases of Clonorchis sinensis in Response to the Host Bile and Oxidative Stressors

    Science.gov (United States)

    Bae, Young-An; Ahn, Do-Whan; Lee, Eung-Goo; Kim, Seon-Hee; Cai, Guo-Bin; Kang, Insug; Sohn, Woon-Mok; Kong, Yoon

    2013-01-01

    Background Clonorchis sinensis causes chronic cumulative infections in the human hepatobiliary tract and is intimately associated with cholangiocarcinoma. Approximately 35 million people are infected and 600 million people are at risk of infections worldwide. C. sinensis excretory-secretory products (ESP) constitute the first-line effector system affecting the host-parasite interrelationship by interacting with bile fluids and ductal epithelium. However, the secretory behavior of C. sinensis in an environment close to natural host conditions is unclear. C. sinensis differs from Fasciola hepatica in migration to, and maturation in, the hepatic bile duct, implying that protein profile of the ESP of these two trematodes might be different from each other. Methodology/Principal Findings We conducted systemic approaches to analyze the C. sinensis ESP proteome and the biological reactivity of C. sinensis glutathione transferases (GSTs), such as global expression patterns and induction profiles under oxidative stress and host bile. When we observed ex host excretion behavior of C. sinensis in the presence of 10% host bile, the global proteome pattern was not significantly altered, but the amount of secretory proteins was increased by approximately 3.5-fold. Bioactive molecules secreted by C. sinensis revealed universal/unique features in relation to its intraluminal hydrophobic residing niche. A total of 38 protein spots identified abundantly included enzymes involved in glucose metabolism (11 spots, 28.9%) and diverse-classes of glutathione transferases (GSTs; 10 spots, 26.3%). Cathepsin L/F (four spots, 10.5%) and transporter molecules (three spots, 7.9%) were also recognized. The universal secretory proteins found in other parasites, such as several enzymes involved in glucose metabolism and oxygen transporters, were commonly detected. C. sinensis secreted less cysteine proteases and fatty acid binding proteins compared to other tissue-invading or intravascular

  16. Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies

    Energy Technology Data Exchange (ETDEWEB)

    Dusinska, Maria, E-mail: Maria.DUSINSKA@nilu.no [CEE-Health Effects Group, NILU - Norwegian Institute for Air Research, Kjeller (Norway); Staruchova, Marta; Horska, Alexandra [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia); Smolkova, Bozena [Laboratory of Cancer Genetics, Cancer Research Institute of the Slovak Academy of Sciences, Bratislava (Slovakia); Collins, Andrew [Department of Nutrition, Faculty of Medicine, University of Oslo (Norway); Bonassi, Stefano [Unit of Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Rome (Italy); Volkovova, Katarina [Department of Experimental and Applied Genetics, Slovak Medical University, Bratislava (Slovakia)

    2012-08-01

    Glutathione S-transferases (GSTs) are members of a multigene family of isoenzymes that are important in the control of oxidative stress and in phase II metabolism. Acting non-enzymically, GSTs can modulate signalling pathways of cell proliferation, cell differentiation and apoptosis. Using a molecular epidemiology approach, we have investigated a potential involvement of GSTs in DNA damage processing, specifically the modulation of DNA repair in a group of 388 healthy adult volunteers; 239 with at least 5 years of occupational exposure to asbestos, stone wool or glass fibre, and 149 reference subjects. We measured DNA damage in lymphocytes using the comet assay (alkaline single cell gel electrophoresis): strand breaks (SBs) and alkali-labile sites, oxidised pyrimidines with endonuclease III, and oxidised purines with formamidopyrimidine DNA glycosylase. We also measured GST activity in erythrocytes, and the capacity for base excision repair (BER) in a lymphocyte extract. Polymorphisms in genes encoding three GST isoenzymes were determined, namely deletion of GSTM1 and GSTT1 and single nucleotide polymorphism Ile105Val in GSTP1. Consumption of vegetables and wine correlated negatively with DNA damage and modulated BER. GST activity correlated with oxidised bases and with BER capacity, and differed depending on polymorphisms in GSTP1, GSTT1 and GSTM1. A significantly lower BER rate was associated with the homozygous GSTT1 deletion in all asbestos site subjects and in the corresponding reference group. Multifactorial analysis revealed effects of sex and exposure in GSTP1 Ile/Val heterozygotes but not in Ile/Ile homozygotes. These variants affected also SBs levels, mainly by interactions of GSTP1 genotype with exposure, with sex, and with smoking habit; and by an interaction between sex and smoking. Our results show that GST polymorphisms and GST activity can apparently influence DNA stability and repair of oxidised bases, suggesting a potential new role for these

  17. Biochemical Characterization and Vaccine Potential of a Heme-Binding Glutathione Transferase from the Adult Hookworm Ancylostoma caninum

    Science.gov (United States)

    Zhan, Bin; Liu, Sen; Perally, Samirah; Xue, Jian; Fujiwara, Ricardo; Brophy, Peter; Xiao, Shuhua; Liu, Yueyuan; Feng, Jianjun; Williamson, Angela; Wang, Yan; Bueno, Lilian L.; Mendez, Susana; Goud, Gaddam; Bethony, Jeffrey M.; Hawdon, John M.; Loukas, Alex; Jones, Karen; Hotez, Peter J.

    2005-01-01

    We report the cloning and expression of Ac-GST-1, a novel glutathione S-transferase from the adult hookworm Ancylostoma caninum, and its possible role in parasite blood feeding and as a vaccine target. The predicted Ac-GST-1 open reading frame contains 207 amino acids (mass, 24 kDa) and exhibited up to 65% amino acid identity with other nematode GSTs. mRNA encoding Ac-GST-1 was detected in adults, eggs, and larval stages, but the protein was detected only in adult hookworm somatic extracts and excretory/secretory products. Using antiserum to the recombinant protein, Ac-GST-1 was immunolocalized to the parasite hypodermis and muscle tissue and weakly to the intestine. Recombinant Ac-GST-1 was enzymatically active, as determined by conjugation of glutathione to a model substrate, and exhibited a novel high-affinity binding site for hematin. The possible role of Ac-GST-1 in parasite heme detoxification during hemoglobin digestion or heme uptake prompted interest in evaluating it as a potential vaccine antigen. Vaccination of dogs with Ac-GST-1 resulted in a 39.4% reduction in the mean worm burden and 32.3% reduction in egg counts compared to control dogs following larval challenge, although the reductions were not statistically significant. However, hamsters vaccinated with Ac-GST-1 exhibited statistically significant worm reduction (53.7%) following challenge with heterologous Necator americanus larvae. These studies suggest that Ac-GST-1 is a possible drug and vaccine target for hookworm infection. PMID:16177370

  18. Nuclear translocation of glutathione S-transferase {pi} is mediated by a non-classical localization signal

    Energy Technology Data Exchange (ETDEWEB)

    Kawakatsu, Miho [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan); Goto, Shinji, E-mail: sgoto@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan); Yoshida, Takako; Urata, Yoshishige; Li, Tao-Sheng [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8523 (Japan)

    2011-08-12

    Highlights: {yields} Nuclear translocation of GST{pi} is abrogated by the deletion of the last 16 amino acid residues in the carboxy-terminal region, indicating that residues 195-208 of GST{pi} are required for nuclear translocation. {yields} The lack of a contiguous stretch of positively charged amino acid residues within the carboxy-terminal region of GST{pi}, suggests that the nuclear translocation of GST{pi} is mediated by a non-classical nuclear localization signal. {yields} An in vitro transport assay shows that the nuclear translocation of GST{pi} is dependent on cytosolic factors and ATP. -- Abstract: Glutathione S-transferase {pi} (GST{pi}), a member of the GST family of multifunctional enzymes, is highly expressed in human placenta and involved in the protection of cellular components against electrophilic compounds or oxidative stress. We have recently found that GST{pi} is expressed in the cytoplasm, mitochondria, and nucleus in some cancer cells, and that the nuclear expression of GST{pi} appears to correlate with resistance to anti-cancer drugs. Although the mitochondrial targeting signal of GST{pi} was previously identified in the amino-terminal region, the mechanism of nuclear translocation remains completely unknown. In this study, we find that the region of GST{pi}195-208 is critical for nuclear translocation, which is mediated by a novel and non-classical nuclear localization signal. In addition, using an in vitro transport assay, we demonstrate that the nuclear translocation of GST{pi} depends on the cytosolic extract and ATP. Although further experiments are needed to understand in depth the precise mechanism of nuclear translocation of GST{pi}, our results may help to establish more efficient anti-cancer therapy, especially with respect to resistance to anti-cancer drugs.

  19. JS-K, a glutathione S-transferase-activated nitric oxide donor with antineoplastic activity in malignant gliomas.

    Science.gov (United States)

    Weyerbrock, Astrid; Osterberg, Nadja; Psarras, Nikolaos; Baumer, Brunhilde; Kogias, Evangelos; Werres, Anna; Bette, Stefanie; Saavedra, Joseph E; Keefer, Larry K; Papazoglou, Anna

    2012-02-01

    Glutathione S-transferases (GSTs) control multidrug resistance and are upregulated in many cancers, including malignant gliomas. The diazeniumdiolate JS-K generates nitric oxide (NO) on enzymatic activation by glutathione and GST, showing promising NO-based anticancer efficacy. To evaluate the role of NO-based antitumor therapy with JS-K in U87 gliomas in vitro and in vivo. U87 glioma cells and primary glioblastoma cell lines were exposed to JS-K and a variety of inhibitors to study cell death by necrosis, apoptosis, and other mechanisms. GST expression was evaluated by immunocytochemistry, polymerase chain reaction, and Western blot, and NO release from JS-K was studied with a NO assay. The growth-inhibitory effect of JS-K was studied in a U87 xenograft model in vivo. Dose-dependent inhibition of cell proliferation was observed in human U87 glioma cells and primary glioblastoma cells in vitro. Cell death was partially induced by caspase-dependent apoptosis, which could be blocked by Z-VAD-FMK and Q-VD-OPH. Inhibition of GST by sulfasalazine, cGMP inhibition by ODQ, and MEK1/2 inhibition by UO126 attenuated the antiproliferative effect of JS-K, suggesting the involvement of various intracellular death signaling pathways. Response to JS-K correlated with mRNA and protein expression of GST and the amount of NO released by the glioma cells. Growth of U87 xenografts was reduced significantly, with immunohistochemical evidence for increased necrosis and apoptosis and reduced proliferation. Our data show for the first time the potent antiproliferative effect of JS-K in gliomas in vitro and in vivo. These findings warrant further investigation of this novel NO-releasing prodrug in gliomas.

  20. Post-transcriptional generation of miRNA variants by multiple nucleotidyl transferases contributes to miRNA transcriptome complexity.

    Science.gov (United States)

    Wyman, Stacia K; Knouf, Emily C; Parkin, Rachael K; Fritz, Brian R; Lin, Daniel W; Dennis, Lucas M; Krouse, Michael A; Webster, Philippa J; Tewari, Muneesh

    2011-09-01

    Modification of microRNA sequences by the 3' addition of nucleotides to generate so-called "isomiRs" adds to the complexity of miRNA function, with recent reports showing that 3' modifications can influence miRNA stability and efficiency of target repression. Here, we show that the 3' modification of miRNAs is a physiological and common post-transcriptional event that shows selectivity for specific miRNAs and is observed across species ranging from C. elegans to human. The modifications result predominantly from adenylation and uridylation and are seen across tissue types, disease states, and developmental stages. To quantitatively profile 3' nucleotide additions, we developed and validated a novel assay based on NanoString Technologies' nCounter platform. For certain miRNAs, the frequency of modification was altered by processes such as cell differentiation, indicating that 3' modification is a biologically regulated process. To investigate the mechanism of 3' nucleotide additions, we used RNA interference to screen a panel of eight candidate miRNA nucleotidyl transferases for 3' miRNA modification activity in human cells. Multiple enzymes, including MTPAP, PAPD4, PAPD5, ZCCHC6, ZCCHC11, and TUT1, were found to govern 3' nucleotide addition to miRNAs in a miRNA-specific manner. Three of these enzymes-MTPAP, ZCCHC6, and TUT1-have not previously been known to modify miRNAs. Collectively, our results indicate that 3' modification observed in next-generation small RNA sequencing data is a biologically relevant process, and identify enzymatic mechanisms that may lead to new approaches for modulating miRNA activity in vivo.

  1. Glutathione S-Transferase (GST Gene Diversity in the Crustacean Calanus finmarchicus--Contributors to Cellular Detoxification.

    Directory of Open Access Journals (Sweden)

    Vittoria Roncalli

    Full Text Available Detoxification is a fundamental cellular stress defense mechanism, which allows an organism to survive or even thrive in the presence of environmental toxins and/or pollutants. The glutathione S-transferase (GST superfamily is a set of enzymes involved in the detoxification process. This highly diverse protein superfamily is characterized by multiple gene duplications, with over 40 GST genes reported in some insects. However, less is known about the GST superfamily in marine organisms, including crustaceans. The availability of two de novo transcriptomes for the copepod, Calanus finmarchicus, provided an opportunity for an in depth study of the GST superfamily in a marine crustacean. The transcriptomes were searched for putative GST-encoding transcripts using known GST proteins from three arthropods as queries. The identified transcripts were then translated into proteins, analyzed for structural domains, and annotated using reciprocal BLAST analysis. Mining the two transcriptomes yielded a total of 41 predicted GST proteins belonging to the cytosolic, mitochondrial or microsomal classes. Phylogenetic analysis of the cytosolic GSTs validated their annotation into six different subclasses. The predicted proteins are likely to represent the products of distinct genes, suggesting that the diversity of GSTs in C. finmarchicus exceeds or rivals that described for insects. Analysis of relative gene expression in different developmental stages indicated low levels of GST expression in embryos, and relatively high expression in late copepodites and adult females for several cytosolic GSTs. A diverse diet and complex life history are factors that might be driving the multiplicity of GSTs in C. finmarchicus, as this copepod is commonly exposed to a variety of natural toxins. Hence, diversity in detoxification pathway proteins may well be key to their survival.

  2. Effects of three pesticides on superoxide dismutase and glutathione-S-transferase activities and reproduction of Daphnia magna

    Directory of Open Access Journals (Sweden)

    Song Yuzhi

    2017-03-01

    Full Text Available Applying pesticides to crops is one of the causes of water pollution by surface runoff, and chlorpyrifos, trifluralin and chlorothalonil are used respectively as insecticide, herbicide and fungicide for crop plants widely. To explore effects of three pesticides on aquatic organisms, superoxide dismutase (SOD and glutathione S-transferase (GST activities were determined after 24 h and 48 h exposure of D. magna with ages of 6–24 h to several low concentrations of chlorpyrifos (0.36, 0.72, 1.43, 2.86, 5.72 μg∙L−1, trifluralin (0.17, 0.33, 0.66, 1.33, 2.65 mg∙L−1 and chlorothalonil (0.09, 0.18, 0.36, 0.72, 1.43 mg∙L−1 respectively. Main reproductive parameters including first pregnancy time, first brood time, the number of first brood and total fecundity after 21 d exposures at the same concentrations of pesticides as described above were also measured. The results showed that the activities of GST increased in lower concentrations and decreased in higher concentrations after 24 h exposure to three pesticides, respectively. The activities of SOD showed the same changes after 48 h exposure. With the time prolonged, the activities of GST decreased while the activities of SOD increased. After 21 d exposure, the first pregnancy time and first brood time were delayed, while the number of the first brood and total fecundity per female decreased with increasing concentrations. These results corroborated that GST activity was more sensitive to those pesticides than SOD activity, and there was a significant relationship between total fecundity and pesticides-dose(r>0.94, n=6, GST activity after 48 h exposure and total fecundity after 21 d exposure (r>0.92, n=6.

  3. Are glutathione S transferases involved in DNA damage signalling? Interactions with DNA damage and repair revealed from molecular epidemiology studies

    International Nuclear Information System (INIS)

    Dusinska, Maria; Staruchova, Marta; Horska, Alexandra; Smolkova, Bozena; Collins, Andrew; Bonassi, Stefano; Volkovova, Katarina

    2012-01-01

    Glutathione S-transferases (GSTs) are members of a multigene family of isoenzymes that are important in the control of oxidative stress and in phase II metabolism. Acting non-enzymically, GSTs can modulate signalling pathways of cell proliferation, cell differentiation and apoptosis. Using a molecular epidemiology approach, we have investigated a potential involvement of GSTs in DNA damage processing, specifically the modulation of DNA repair in a group of 388 healthy adult volunteers; 239 with at least 5 years of occupational exposure to asbestos, stone wool or glass fibre, and 149 reference subjects. We measured DNA damage in lymphocytes using the comet assay (alkaline single cell gel electrophoresis): strand breaks (SBs) and alkali-labile sites, oxidised pyrimidines with endonuclease III, and oxidised purines with formamidopyrimidine DNA glycosylase. We also measured GST activity in erythrocytes, and the capacity for base excision repair (BER) in a lymphocyte extract. Polymorphisms in genes encoding three GST isoenzymes were determined, namely deletion of GSTM1 and GSTT1 and single nucleotide polymorphism Ile105Val in GSTP1. Consumption of vegetables and wine correlated negatively with DNA damage and modulated BER. GST activity correlated with oxidised bases and with BER capacity, and differed depending on polymorphisms in GSTP1, GSTT1 and GSTM1. A significantly lower BER rate was associated with the homozygous GSTT1 deletion in all asbestos site subjects and in the corresponding reference group. Multifactorial analysis revealed effects of sex and exposure in GSTP1 Ile/Val heterozygotes but not in Ile/Ile homozygotes. These variants affected also SBs levels, mainly by interactions of GSTP1 genotype with exposure, with sex, and with smoking habit; and by an interaction between sex and smoking. Our results show that GST polymorphisms and GST activity can apparently influence DNA stability and repair of oxidised bases, suggesting a potential new role for these

  4. Overlapping protective roles for glutathione transferase gene family members in chemical and oxidative stress response in Agrobacterium tumefaciens.

    Science.gov (United States)

    Skopelitou, Katholiki; Muleta, Abdi W; Pavli, Ourania; Skaracis, Georgios N; Flemetakis, Emmanouil; Papageorgiou, Anastassios C; Labrou, Nikolaos E

    2012-03-01

    In the present work, we describe the characterisation of the glutathione transferase (GST) gene family from Agrobacterium tumefaciens C58. A genome survey revealed the presence of eight GST-like proteins in A. tumefaciens (AtuGSTs). Comparison by multiple sequence alignment generated a dendrogram revealing the phylogenetic relationships of AtuGSTs-like proteins. The beta and theta classes identified in other bacterial species are represented by five members in A. tumefaciens C58. In addition, there are three "orphan" sequences that do not fit into any previously recognised GST classes. The eight GST-like genes were cloned, expressed in Escherichia coli and their substrate specificity was determined towards 17 different substrates. The results showed that AtuGSTs catalyse a broad range of reactions, with different members of the family exhibiting quite varied substrate specificity. The 3D structures of AtuGSTs were predicted using molecular modelling. The use of comparative sequence and structural analysis of the AtuGST isoenzymes allowed us to identify local sequence and structural characteristics between different GST isoenzymes and classes. Gene expression profiling was conducted under normal culture conditions as well as under abiotic stress conditions (addition of xenobiotics, osmotic stress and cold and heat shock) to induce and monitor early stress-response mechanisms. The results reveal the constitutive expression of GSTs in A. tumefaciens and a modulation of GST activity after treatments, indicating that AtuGSTs presumably participate in a wide range of functions, many of which are important in counteracting stress conditions. These functions may be relevant to maintaining cellular homeostasis as well as in the direct detoxification of toxic compounds.

  5. Cys-X scanning for expansion of active-site residues and modulation of catalytic functions in a glutathione transferase.

    Science.gov (United States)

    Norrgård, Malena A; Hellman, Ulf; Mannervik, Bengt

    2011-05-13

    We propose Cys-X scanning as a semisynthetic approach to engineer the functional properties of recombinant proteins. As in the case of Ala scanning, key residues in the primary structure are identified, and one of them is replaced by Cys via site-directed mutagenesis. The thiol of the residue introduced is subsequently modified by alternative chemical reagents to yield diverse Cys-X mutants of the protein. This chemical approach is orthogonal to Ala or Cys scanning and allows the expansion of the repertoire of amino acid side chains far beyond those present in natural proteins. In its present application, we have introduced Cys-X residues in human glutathione transferase (GST) M2-2, replacing Met-212 in the substrate-binding site. To achieve selectivity of the modifications, the Cys residues in the wild-type enzyme were replaced by Ala. A suite of simple substitutions resulted in a set of homologous Met derivatives ranging from normethionine to S-heptyl-cysteine. The chemical modifications were validated by HPLC and mass spectrometry. The derivatized mutant enzymes were assayed with alternative GST substrates representing diverse chemical reactions: aromatic substitution, epoxide opening, transnitrosylation, and addition to an ortho-quinone. The Cys substitutions had different effects on the alternative substrates and differentially enhanced or suppressed catalytic activities depending on both the Cys-X substitution and the substrate assayed. As a consequence, the enzyme specificity profile could be changed among the alternative substrates. The procedure lends itself to large-scale production of Cys-X modified protein variants.

  6. Correlation between serum and peritoneal fluid glutathione S-transferases T1 concentration with different stages of endometriosis

    Directory of Open Access Journals (Sweden)

    Sohail Mashayekhi

    2018-03-01

    Full Text Available Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Ectopic endometrial cell proliferation and chronic inflammation in endometriosis were shown to be associated with oxidative stress (OS induction. OS is a condition in which reactive oxygen species (ROS overproduction and antioxidant deficiency cause a shift in oxidant/antioxidant balance. Glutathione S-transferases (GSTs comprise a family of eukaryotic and prokaryotic phase II metabolic isozymes best known for their ability to catalyze the conjugation of the reduced form of glutathione (GSH to xenobiotic substrates for the purpose of detoxification. The aim of this project was to study the concentrations of GSTT1 in the serum and peritoneal fluid (PF of patients with different stages of endometriosis. Frothy two PF and serum from normal and 152 from different stages of patients with endometriosis (stage I: n = 30, stage II: n = 39, stage III: n = 43 and stage IV: n = 40 were included in this study. The level of GSTT1 in the serum was determined by enzyme linked immunosorbent assay (ELISA. The results showed the presence of GSTT1 in all serum and peritoneal fluid samples, while, starting from stages I to IV endometriosis, a significant decrease in GSTT1 concentration was seen as compared to controls. It is concluded that levels of GSTT1 is negatively correlated with advanced stages of endometriosis. It is also suggested that the detection of serum and/or peritoneal fluid GSTT1 concentration may be valuable in the classifying of endometriosis.

  7. SILENCING THE NUCLEOCYTOPLASMIC O-GLCNAC TRANSFERASE REDUCES PROLIFERATION, ADHESION AND MIGRATION OF CANCER AND FETAL HUMAN COLON CELL LINES

    Directory of Open Access Journals (Sweden)

    AGATA eSTEENACKERS

    2016-05-01

    Full Text Available The post-translational modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc is regulated by a unique couple of enzymes. O-GlcNAc transferase (OGT transfers the GlcNAc residue from UDP-GlcNAc, the final product of the hexosamine biosynthetic pathway (HBP, whereas O-GlcNAcase (OGA removes it. This study and others show that OGT and O-GlcNAcylation levels are increased in cancer cell lines. In that context we studied the effect of OGT silencing in the colon cancer cell lines HT29 and HCT116 and the primary colon cell line CCD841CoN. Herein we report that OGT silencing diminished proliferation, in vitro cell survival and adhesion of primary and cancer cell lines. SiOGT dramatically de-creased HT29 and CCD841CoN migration, CCD841CoN harboring high capabilities of mi-gration in Boyden chamber system when compared to HT29 and HCT116. The expression levels of actin and tubulin were unaffected by OGT knockdown but siOGT seemed to disor-ganize microfilament, microtubule and vinculin networks in CCD841CoN. While cancer cell lines harbor higher levels of OGT and O-GlcNAcylation to fulfill their proliferative and migra-tory properties, in agreement with their higher consumption of HBP main substrates glucose and glutamine, our data demonstrate that OGT expression is not only necessary for the biolog-ical properties of cancer cell lines but also for normal cells.

  8. Novel function of glutathione transferase in rat liver mitochondrial membrane: Role for cytochrome c release from mitochondria

    International Nuclear Information System (INIS)

    Lee, Kang Kwang; Shimoji, Manami; Hossain, Quazi Sohel; Sunakawa, Hajime; Aniya, Yoko

    2008-01-01

    Microsomal glutathione transferase (MGST1) is activated by oxidative stress. Although MGST1 is found in mitochondrial membranes (mtMGST1), there is no information about the oxidative activation of mtMGST1. In the present study, we aimed to determine whether mtMGST1 also undergoes activation and about its function. When rats were treated with galactosamine/lipopolysaccharide (GalN/LPS), mtMGST1 activity was significantly increased, and the increased activity was reduced by the disulfide reducing agent dithiothreitol. In mitochondria from GalN/LPS-treated rats, disulfide-linked mtMGST1 dimer and mixed protein glutathione disulfides (glutathionylation) were detected. In addition, cytochrome c release from mitochondria isolated from GalN/LPS-treated rats was observed, and the release was inhibited by anti-MGST1 antibodies. Incubation of mitochondria from control rats with diamide and diamide plus GSH in vitro resulted in dimer- and mixed disulfide bond-mediated activation of mtMGST1, respectively. The activation of mtMGST1 by diamide plus GSH caused cytochrome c release from the mitochondria, and the release was prevented by treatment with anti-MGST1 antibodies. In addition, diamide plus GSH treatment caused mitochondrial swelling accompanied by cytochrome c release, which was inhibited by cyclosporin A (CsA) and bongkrekic acid (BKA), inhibitors of the mitochondrial permeability transition (MPT) pore. Furthermore, mtMGST1 activity was also inhibited by CsA and BKA. These results indicate that mtMGST1 is activated through mixed disulfide bond formation that contributes to cytochrome c release from mitochondria through the MPT pore

  9. Microsomal Glutathione Transferase 1 Protects Against Toxicity Induced by Silica Nanoparticles but Not by Zinc Oxide Nanoparticles

    Science.gov (United States)

    2012-01-01

    Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO2, CeO2, SiO2, and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO2 and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO2 and CeO2. We also noted pronounced cytotoxicity for three out of four additional SiO2 nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO2 nanoparticles tested and for one of the supplementary SiO2 nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO2 nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn2+ with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn2+ could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO2 nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum. PMID:22303956

  10. Molecular cloning, heterologous expression and functional characterization of gamma tocopherol methyl transferase (γ-TMT) from Glycine max.

    Science.gov (United States)

    Tewari, Kalpana; Dahuja, Anil; Sachdev, Archana; Kumar, Vaibhav; Ali, Kishwar; Kumar, Amresh; Kumari, Sweta

    2017-12-01

    γ-Tocopherol methyltransferase (γ-TMT) (EC 2.1.1.95) is the last enzyme in the tocopherol biosynthetic pathway and it catalyzes the conversion of γ-tocopherol into α-tocopherol, the nutritionally significant and most bioactive form of vitamin E. Although the γ-TMT gene has been successfully overexpressed in many crops to enhance their α-tocopherol content but still only few attempts have been made to uncover its structural, functional and regulation aspects at protein level. In this study, we have cloned the complete 909bp coding sequence of Glycine max γ-TMT (Gm γ-TMT) gene that encodes the corresponding protein comprising of 302 amino acid residues. The deduced Gm γ-TMT protein showed 74-87% sequence identity with other characterized plant γ-TMTs. Gm γ-TMT belongs to Class I Methyl Transferases that have a Rossmann-like fold which consists of a seven-stranded β sheet joined by α helices. Heterologous expression of Gm γ-TMT in pET29a expression vector under the control of bacteriophage T7 promoter produced a 37.9 kDa recombinant Gm γ-TMT protein with histidine hexamer tag at its C-terminus. The expression of recombinant Gm γ-TMT protein was confirmed by western blotting using anti-His antibody. The recombinant protein was purified by Ni 2+ -NTA column chromatography. The purified protein showed SAM dependent methyltransferase activity. The α-tocopherol produced in the in-vitro reaction catalyzed by the purified enzyme was detected using reverse phase HPLC. This study has laid the foundation to unveil the biochemical understanding of Gm γ-TMT enzyme which can be further explored by studying its kinetic behaviour, substrate specificity and its interaction with other biomolecules. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effect of recombinant glutathione S-transferase as vaccine antigen against Rhipicephalus appendiculatus and Rhipicephalus sanguineus infestation.

    Science.gov (United States)

    Sabadin, Gabriela Alves; Parizi, Luís Fernando; Kiio, Irene; Xavier, Marina Amaral; da Silva Matos, Renata; Camargo-Mathias, Maria Izabel; Githaka, Naftaly Wang'ombe; Nene, Vish; da Silva Vaz, Itabajara

    2017-12-04

    The ticks Rhipicephalus appendiculatus and Rhipicephalus sanguineus are the main vectors of Theileria parva and Babesia spp. in cattle and dogs, respectively. Due to their impact in veterinary care and industry, improved methods against R. appendiculatus and R. sanguineus parasitism are under development, including vaccines. We have previously demonstrated the induction of a cross-protective humoral response against Rhipicephalus microplus following vaccination with recombinant glutathione S-transferase from Haemaphysalis longicornis tick (rGST-Hl), suggesting that this protein could control tick infestations. In the present work, we investigated the effect of rGST-Hl vaccine against R. appendiculatus and R. sanguineus infestation in rabbits. In silico analysis revealed that GST from H. longicornis, R. appendiculatus and R. sanguineus have >80% protein sequence similarity, and multiple conserved antigenic sites. After the second vaccine dose, rGST-Hl-immunized rabbits showed elevated antibody levels which persisted until the end of experiment (75 and 60 days for R. appendiculatus and R. sanguineus, respectively). Western blot assays demonstrated cross-reactivity between anti-rGST-Hl antibodies and native R. appendiculatus and R. sanguineus GST extracts from ticks at different life stages. Vaccination with rGST-Hl decreased the number, weight, and fertility of engorged R. appendiculatus adults, leading to an overall vaccine efficacy of 67%. Interestingly, histological analysis of organ morphology showed damage to salivary glands and ovaries of R. appendiculatus adult females fed on vaccinated animals. In contrast, rGST-Hl vaccination did not affect R. appendiculatus nymphs, and it was ineffective against R. sanguineus across the stages of nymph and adult. Taken together, our results show the potential application of rGST-Hl as an antigen in anti-tick vaccine development, however indicating a broad difference in efficacy among tick species. Copyright © 2017 Elsevier

  12. Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiyuan [Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of); An, Byoung Ha [Department of Food and Nutrition, College of Life Science, Sookmyung Women’s University, Seoul (Korea, Republic of); Kim, Min Jung; Park, Jong Hoon [Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of); Kang, Young Sook [Department of Pharmacy, College of Pharmacy, Sookmyung Women’s University, Seoul (Korea, Republic of); Chang, Minsun, E-mail: minsunchang@sm.ac.kr [Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women’s University, Seoul (Korea, Republic of)

    2014-09-26

    Highlights: • GSTP induces the classical ERα signaling event. • The functional GSTP is a prerequisite for GSTP-induced ERα transcription activity. • The expression of RIP140, a transcription cofactor, was inhibited by GSTP protein. • We propose the novel non-enzymatic role of GSTP. - Abstract: Estrogen receptor α (ERα) plays a crucial role in estrogen-mediated signaling pathways and exerts its action as a nuclear transcription factor. Binding of the ligand-activated ERα to the estrogen response element (ERE) is a central part of ERα-associated signal transduction pathways and its aberrant modulation is associated with many disease conditions. Human glutathione S-transferase P1-1 (GSTP) functions as an enzyme in conjugation reactions in drug metabolism and as a regulator of kinase signaling pathways. It is overexpressed in tumors following chemotherapy and has been associated with a poor prognosis in breast cancer. In this study, a novel regulatory function of GSTP has been proposed in which GSTP modulates ERE-mediated ERα signaling events. Ectopic expression of GSTP was able to induce the ERα and ERE-mediated transcriptional activities in ERα-positive but GSTP-negative MCF7 human breast cancer cells. This inductive effect of GSTP on the ERE-transcription activity was diminished when the cells express a mutated form of the enzyme or are treated with a GSTP-specific chemical inhibitor. It was found that GSTP inhibited the expression of the receptor interacting protein 140 (RIP140), a negative regulator of ERα transcription, at both mRNA and protein levels. Our study suggests a novel non-enzymatic role of GSTP which plays a significant role in regulating the classical ERα signaling pathways via modification of transcription cofactors such as RIP140.

  13. Interaction of Ferulic Acid with Glutathione S-Transferase and Carboxylesterase Genes in the Brown Planthopper, Nilaparvata lugens.

    Science.gov (United States)

    Yang, Jun; Sun, Xiao-Qin; Yan, Shu-Ying; Pan, Wen-Jun; Zhang, Mao-Xin; Cai, Qing-Nian

    2017-07-01

    Plant phenolics are crucial defense phytochemicals against herbivores and glutathione S-transferase (GST) and carboxylesterase (CarE) in herbivorous insects are well-known detoxification enzymes for such xenobiotics. To understand relationship between a plant phenolic and herbivore GST or CarE genes, we evaluated the relationship between a rice phenolic ferulic acid and resistance to brown planthopper (BPH, Nilaparvata lugens), and investigated the interaction of ferulic acid with GST or CarE genes in BPH. The results indicate that ferulic acid content in tested rice varieties was highly associated with resistance to BPH. Bioassays using artificial diets show that the phenolic acid toxicity to BPH was dose dependent and the LC 25 and LC 50 were 5.81 and 23.30 μg/ml at 72 hr, respectively. Activities of the enzymes BPH GST and CarE were increased at concentrations below the LC 50 of ferulic acid. Moreover, low ferulic acid concentrations (gene silencing (DIGS) of GST or CarE, it was shown that suppressed expression levels of NlGSTD1, NlGSTE1 and NlCE were 14.6%-21.2%, 27.8%-34.2%, and 10.5%-19.8%, respectively. Combination of NlGSTD1, NlGSTE1 or NlCE knockdown with ferulic acid increased nymph mortality by 92.9%, 119.9%, or 124.6%, respectively. These results suggest that depletion of detoxification genes in herbivorous insects by plant-mediated RNAi technology might be a new potential resource for improving rice resistance to BPH.

  14. Systemic catechol-O-methyl transferase inhibition enables the D1 agonist radiotracer R-[11C]SKF 82957

    International Nuclear Information System (INIS)

    Palner, Mikael; McCormick, Patrick; Parkes, Jun; Knudsen, Gitte M.; Wilson, Alan A.

    2010-01-01

    Introduction: R-[ 11 C]-SKF 82957 is a high-affinity and potent dopamine D 1 receptor agonist radioligand, which gives rise to a brain-penetrant lipophilic metabolite. In this study, we demonstrate that systemic administration of catechol-O-methyl transferase (COMT) inhibitors blocks this metabolic pathway, facilitating the use of R-[ 11 C]-SKF 82957 to image the high-affinity state of the dopamine D 1 receptor with PET. Methods: R-[ 11 C]SKF 82957 was administered to untreated and COMT inhibitor-treated conscious rats, and the radioactive metabolites present in the brain and plasma were quantified by HPLC. Under optimal conditions, cerebral uptake and dopamine D 1 binding of R-[ 11 C]SKF 82957 were measured ex vivo. In addition, pharmacological challenges with the receptor antagonist SCH 23390, amphetamine, the dopamine reuptake inhibitor RTI-32 and the dopamine hydroxylase inhibitor α-methyl-p-tyrosine were performed to study the specificity and sensitivity of R-[ 11 C]-SKF 82957 dopamine D 1 binding in COMT-inhibited animals. Results: Treatment with the COMT inhibitor tolcapone was associated with a dose-dependent (EC 90 5.3±4.3 mg/kg) reduction in the lipophilic metabolite. Tolcapone treatment (20 mg/kg) also resulted in a significant increase in the striatum/cerebellum ratio of R-[ 11 C]SKF 82957, from 15 (controls) to 24. Treatment with the dopamine D 1 antagonist SCH 23390 reduced the striatal binding to the levels of the cerebellum, demonstrating a high specificity and selectivity of R-[ 11 C]SKF 82957 binding. Conclusions: Pre-treatment with the COMT inhibitor tolcapone inhibits formation of an interfering metabolite of R-[ 11 C]SKF 82957. Under such conditions, R-[ 11 C]SKF 82957 demonstrates high potential as the first agonist radiotracer for imaging the dopamine D 1 receptor by PET.

  15. Growth hormone alters the glutathione S-transferase and mitochondrial thioredoxin systems in long-living Ames dwarf mice.

    Science.gov (United States)

    Rojanathammanee, Lalida; Rakoczy, Sharlene; Brown-Borg, Holly M

    2014-10-01

    Ames dwarf mice are deficient in growth hormone (GH), prolactin, and thyroid-stimulating hormone and live significantly longer than their wild-type (WT) siblings. The lack of GH is associated with stress resistance and increased longevity. However, the mechanism underlying GH's actions on cellular stress defense have yet to be elucidated. In this study, WT or Ames dwarf mice were treated with saline or GH (WT saline, Dwarf saline, and Dwarf GH) two times daily for 7 days. The body and liver weights of Ames dwarf mice were significantly increased after 7 days of GH administration. Mitochondrial protein levels of the glutathione S-transferase (GST) isozymes, K1 and M4 (GSTK1 and GSTM4), were significantly higher in dwarf mice (Dwarf saline) when compared with WT mice (WT saline). GH administration downregulated the expression of GSTK1 proteins in dwarf mice. We further investigated GST activity from liver lysates using different substrates. Substrate-specific GST activity (bromosulfophthalein, dichloronitrobenzene, and 4-hydrox-ynonenal) was significantly reduced in GH-treated dwarf mice. In addition, GH treatment attenuated the activity of thioredoxin and glutaredoxin in liver mitochondria of Ames mice. Importantly, GH treatment suppressed Trx2 and TrxR2 mRNA expression. These data indicate that GH has a role in stress resistance by altering the functional capacity of the GST system through the regulation of specific GST family members in long-living Ames dwarf mice. It also affects the regulation of thioredoxin and glutaredoxin, factors that regulate posttranslational modification of proteins and redox balance, thereby further influencing stress resistance. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Large-scale determination of sequence, structure, and function relationships in cytosolic glutathione transferases across the biosphere.

    Science.gov (United States)

    Mashiyama, Susan T; Malabanan, M Merced; Akiva, Eyal; Bhosle, Rahul; Branch, Megan C; Hillerich, Brandan; Jagessar, Kevin; Kim, Jungwook; Patskovsky, Yury; Seidel, Ronald D; Stead, Mark; Toro, Rafael; Vetting, Matthew W; Almo, Steven C; Armstrong, Richard N; Babbitt, Patricia C

    2014-04-01

    The cytosolic glutathione transferase (cytGST) superfamily comprises more than 13,000 nonredundant sequences found throughout the biosphere. Their key roles in metabolism and defense against oxidative damage have led to thousands of studies over several decades. Despite this attention, little is known about the physiological reactions they catalyze and most of the substrates used to assay cytGSTs are synthetic compounds. A deeper understanding of relationships across the superfamily could provide new clues about their functions. To establish a foundation for expanded classification of cytGSTs, we generated similarity-based subgroupings for the entire superfamily. Using the resulting sequence similarity networks, we chose targets that broadly covered unknown functions and report here experimental results confirming GST-like activity for 82 of them, along with 37 new 3D structures determined for 27 targets. These new data, along with experimentally known GST reactions and structures reported in the literature, were painted onto the networks to generate a global view of their sequence-structure-function relationships. The results show how proteins of both known and unknown function relate to each other across the entire superfamily and reveal that the great majority of cytGSTs have not been experimentally characterized or annotated by canonical class. A mapping of taxonomic classes across the superfamily indicates that many taxa are represented in each subgroup and highlights challenges for classification of superfamily sequences into functionally relevant classes. Experimental determination of disulfide bond reductase activity in many diverse subgroups illustrate a theme common for many reaction types. Finally, sequence comparison between an enzyme that catalyzes a reductive dechlorination reaction relevant to bioremediation efforts with some of its closest homologs reveals differences among them likely to be associated with evolution of this unusual reaction

  17. Large-scale determination of sequence, structure, and function relationships in cytosolic glutathione transferases across the biosphere.

    Directory of Open Access Journals (Sweden)

    Susan T Mashiyama

    2014-04-01

    Full Text Available The cytosolic glutathione transferase (cytGST superfamily comprises more than 13,000 nonredundant sequences found throughout the biosphere. Their key roles in metabolism and defense against oxidative damage have led to thousands of studies over several decades. Despite this attention, little is known about the physiological reactions they catalyze and most of the substrates used to assay cytGSTs are synthetic compounds. A deeper understanding of relationships across the superfamily could provide new clues about their functions. To establish a foundation for expanded classification of cytGSTs, we generated similarity-based subgroupings for the entire superfamily. Using the resulting sequence similarity networks, we chose targets that broadly covered unknown functions and report here experimental results confirming GST-like activity for 82 of them, along with 37 new 3D structures determined for 27 targets. These new data, along with experimentally known GST reactions and structures reported in the literature, were painted onto the networks to generate a global view of their sequence-structure-function relationships. The results show how proteins of both known and unknown function relate to each other across the entire superfamily and reveal that the great majority of cytGSTs have not been experimentally characterized or annotated by canonical class. A mapping of taxonomic classes across the superfamily indicates that many taxa are represented in each subgroup and highlights challenges for classification of superfamily sequences into functionally relevant classes. Experimental determination of disulfide bond reductase activity in many diverse subgroups illustrate a theme common for many reaction types. Finally, sequence comparison between an enzyme that catalyzes a reductive dechlorination reaction relevant to bioremediation efforts with some of its closest homologs reveals differences among them likely to be associated with evolution of this

  18. Role of induced glutathione-S-transferase from Helicoverpa armigera (Lepidoptera: Noctuidae) HaGST-8 in detoxification of pesticides.

    Science.gov (United States)

    Labade, Chaitali P; Jadhav, Abhilash R; Ahire, Mehul; Zinjarde, Smita S; Tamhane, Vaijayanti A

    2018-01-01

    The present study deals with glutathione-S-transferase (GST) based detoxification of pesticides in Helicoverpa armigera and its potential application in eliminating pesticides from the environment. Dietary exposure of a pesticide mixture (organophosphates - chlorpyrifos and dichlorvos, pyrethroid - cypermethrin; 2-15ppm each) to H. armigera larvae resulted in a dose dependant up-regulation of GST activity and gene expression. A variant GST from H. armigera (HaGST-8) was isolated from larvae fed with 10ppm pesticide mixture and it was recombinantly expressed in yeast (Pichia pastoris HaGST-8). HaGST-8 had a molecular mass of 29kDa and was most active at pH 9 at 30°C. GC-MS and LC-HRMS analysis validated that HaGST-8 was effective in eliminating organophosphate type of pesticides and partially reduced the cypermethrin content (53%) from aqueous solutions. Unlike the untransformed yeast, P. pastoris HaGST-8 grew efficiently in media supplemented with pesticide mixtures (200 and 400ppm each pesticide) signifying the detoxification ability of HaGST-8. The amino acid sequence of HaGST-8 and the already reported sequence of HaGST-7 had just 2 mismatches. The studies on molecular interaction strengths revealed that HaGST-8 had stronger binding affinities with organophosphate, pyrethroid, organochloride, carbamate and neonicotinoid type of pesticides. The abilities of recombinant HaGST-8 to eliminate pesticides and P. pastoris HaGST-8 to grow profusely in the presence of high level of pesticide content can be applied for removal of such residues from food, water resources and bioremediation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Contribution of Arginine 13 to the Catalytic Activity of Human Class Pi Glutathione Transferase P1-1

    International Nuclear Information System (INIS)

    Kong, Ji Na; Jo, Dong Hyeon; Do, Hyun Dong; Lee, Jin Ju; Kong, Kwang Hoon

    2010-01-01

    Arg13 is a conserved active-site residue in all known Pi class glutathione S-transferases (GSTs) and in most Alpha class GSTs. To evaluate its contribution to substrate binding and catalysis of this residue, three mutants (R13A, R13K, and R13L) were expressed in Escherichia coli and purified by GSH affinity chromatography. The substitutions of Arg13 significantly affected GSH-conjugation activity, while scarcely affecting glutathione peroxidase or steroid isomerase activities. Mutation of Arg13 into Ala largely reduced the GSH-conjugation activity by approximately 85 - 95%, whereas substitutions by Lys and Leu barely affected activity. These results suggest that, in the GSH-conjugation activity of hGST P1-1, the contribution of Arg13 toward catalytic activity is highly dependent on substrate specificities and the size of the side chain at position 13. From the kinetic parameters, introduction of larger side chains at position 13 results in stronger affinity (Leu > Lys, Arg > Ala) towards GSH. The substitutions of Arg13 with alanine and leucine significantly affected k cat , whereas substitution with Lys was similar to that of the wild type, indicating the significance of a positively charged residue at position 13. From the plots of log (k cat /K m CDNB ) against pH, the pK a values of the thiol group of GSH bound in R13A, R13K, and R13L were estimated to be 1.8, 1.4, and 1.8 pK units higher than the pK a value of the wildtype enzyme, demonstrating the contribution of the Arg13 guanidinium group to the electrostatic field in the active site. From these results, we suggest that contribution of Arg13 in substrate binding is highly dependent on the nature of the electrophilic substrates, while in the catalytic mechanism, it stabilizes the GSH thiolate through hydrogen bonding

  20. Are glutathione S-transferase polymorphisms (GSTM1, GSTT1) associated with primary open angle glaucoma? A meta-analysis.

    Science.gov (United States)

    Lu, Yan; Shi, Yuhua; Yin, Jie; Huang, Zhenping

    2013-09-15

    Glutathione S-transferase (GST) variants have been considered as risk factors for the pathogenesis of primary open angle glaucoma (POAG). However, the results have been inconsistent. In this study, we performed a meta-analysis to assess the association between GSTM1 and GSTT1 null genotypes and the risk for POAG. Published literature from PubMed and EMBASE databases was retrieved. All studies evaluating the association between GSTM1/GSTT1 variants and POAG were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effects model. 14 studies (1711 POAG cases and 1537 controls) were included in the meta-analysis of GSTM1 genotypes and 10 studies (1306 POAG cases and 1114 controls) were included in the meta-analysis of GSTT1 genotypes. The overall result showed that the association between GSTM1 and GSTT1 null genotypes and risk for POAG was not statistically significant (GSTM1: OR=1.19, 95% CI=0.82-1.73, p=0.361; GSTT1: OR=1.26, 95% CI=0.77-2.06, p=0.365). The results by ethnicity showed that the association between the GSTM1 null genotype and risk for POAG is statistically significant in East Asians (OR=1.41, 95% CI=1.04-1.90, p=0.026), but not in Caucasians (OR=1.13, 95% CI=0.69-1.84, p=0.638) and Latin-American (OR=1.09, 95% CI=0.62-1.92, p=0.767). In addition, there was no significant association of GSTT1 null genotype with risk for POAG in either ethnic population. The present meta-analysis suggested that there might be a significant association of GSTM1 null genotype with POAG risk in East Asians. © 2013 Elsevier B.V. All rights reserved.

  1. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    Directory of Open Access Journals (Sweden)

    L.C. Carnevali Jr

    2012-08-01

    Full Text Available We examined the capacity of high-intensity intermittent training (HI-IT to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g were randomly distributed into 3 groups: sedentary (Sed, N = 5, HI-IT (N = 10, and moderate-intensity continuous training (MI-CT, N = 10. The trained groups were exercised for 8 weeks with a 10% (HI-IT and a 5% (MI-CT overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01, as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01 and lipoprotein lipase (LPL; P < 0.05. Lactate dehydrogenase also presented a higher maximal activity (nmol·min-1·mg protein-1 in HI-IT (around 83%. We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a "time-efficient" strategy inducing metabolic adaptation.

  2. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    Energy Technology Data Exchange (ETDEWEB)

    Carnevali, L.C. Jr. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Centro Universitário Ítalo-Brasileiro (Unítalo), São Paulo SP (Brazil); Eder, R.; Lira, F.S. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Lima, W.P. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Instituto Federal de Educação,Ciência e Tecnologia de São Paulo, São Paulo SP (Brazil); Gonçalves, D.C. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Zanchi, N.E. [Laboratorio de Nutrição e Metabolismo Aplicado à Atividade Motora, Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo SP (Brazil); Centro de Pesquisa do Genoma Humano, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Nicastro, H. [Laboratorio de Nutrição e Metabolismo Aplicado à Atividade Motora, Escola de Educação Física e Esporte, Universidade de São Paulo, São Paulo SP (Brazil); Lavoie, J.M. [Department of Kinesiology, University of Montreal, Montreal (Canada); Seelaender, M.C.L. [Grupo de Biologia Molecular da Célula, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-06-29

    We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min{sup −1}·mg protein{sup −1}) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a “time-efficient” strategy inducing metabolic adaptation.

  3. Comparative study of acetylcholinesterase and glutathione S-transferase activities of closely related cave and surface Asellus aquaticus (Isopoda: Crustacea.

    Directory of Open Access Journals (Sweden)

    Anita Jemec

    Full Text Available The freshwater isopod crustacean Asellus aquaticus has recently been developed as an emerging invertebrate cave model for studying evolutionary and developmental biology. Mostly morphological and genetic differences between cave and surface A. aquaticus populations have been described up to now, while scarce data are available on other aspects, including physiology. The purpose of this study was to advance our understanding of the physiological differences between cave A. aquaticus and its surface-dwelling counterparts. We sampled two surface populations from the surface section of the sinking Pivka River (central Slovenia, Europe, i.e. locality Pivka Polje, and locality Planina Polje, and one cave population from the subterranean section of the sinking Pivka River, i.e. locality Planina Cave. Animals were sampled in spring, summer and autumn. We measured the activities of acetylcholinesterase (AChE and glutathione S-transferase (GST in individuals snap-frozen in the field immediately after collection. Acetylcholinesterase is likely related to animals' locomotor activity, while GST activity is related to the metabolic activity of an organism. Our study shows significantly lower AChE and GST activities in the cave population in comparison to both surface A. aquaticus populations. This confirms the assumption that cave A. aquaticus have lower locomotor and metabolic activity than surface A. aquaticus in their respective natural environments. In surface A. aquaticus populations, seasonal fluctuations in GST activity were observed, while these were less pronounced in individuals from the more stable cave environment. On the other hand, AChE activity was generally season-independent in all populations. To our knowledge, this is the first study of its kind conducted in A. aquaticus. Our results show that among closely related cave and surface A. aquaticus populations also physiological differences are present besides the morphological and genetic

  4. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats

    International Nuclear Information System (INIS)

    Carnevali, L.C. Jr.; Eder, R.; Lira, F.S.; Lima, W.P.; Gonçalves, D.C.; Zanchi, N.E.; Nicastro, H.; Lavoie, J.M.; Seelaender, M.C.L.

    2012-01-01

    We examined the capacity of high-intensity intermittent training (HI-IT) to facilitate the delivery of lipids to enzymes responsible for oxidation, a task performed by the carnitine palmitoyl transferase (CPT) system in the rat gastrocnemius muscle. Male adult Wistar rats (160-250 g) were randomly distributed into 3 groups: sedentary (Sed, N = 5), HI-IT (N = 10), and moderate-intensity continuous training (MI-CT, N = 10). The trained groups were exercised for 8 weeks with a 10% (HI-IT) and a 5% (MI-CT) overload. The HI-IT group presented 11.8% decreased weight gain compared to the Sed group. The maximal activities of CPT-I, CPT-II, and citrate synthase were all increased in the HI-IT group compared to the Sed group (P < 0.01), as also was gene expression, measured by RT-PCR, of fatty acid binding protein (FABP; P < 0.01) and lipoprotein lipase (LPL; P < 0.05). Lactate dehydrogenase also presented a higher maximal activity (nmol·min −1 ·mg protein −1 ) in HI-IT (around 83%). We suggest that 8 weeks of HI-IT enhance mitochondrial lipid transport capacity thus facilitating the oxidation process in the gastrocnemius muscle. This adaptation may also be associated with the decrease in weight gain observed in the animals and was concomitant to a higher gene expression of both FABP and LPL in HI-IT, suggesting that intermittent exercise is a “time-efficient” strategy inducing metabolic adaptation

  5. Molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases

    Directory of Open Access Journals (Sweden)

    Vasconcelos Vítor

    2010-09-01

    Full Text Available Abstract Background Cytosolic glutathione transferases (cGST are a large group of ubiquitous enzymes involved in detoxification and are well known for their undesired side effects during chemotherapy. In this work we have performed thorough phylogenetic analyses to understand the various aspects of the evolution and functional diversification of cGSTs. Furthermore, we assessed plausible correlations between gene duplication and substrate specificity of gene paralogs in humans and selected species, notably in mammalian enzymes and their natural substrates. Results We present a molecular phylogeny of cytosolic GSTs that shows that several classes of cGSTs are more ubiquitous and thus have an older ancestry than previously thought. Furthermore, we found that positive selection is implicated in the diversification of cGSTs. The number of duplicate genes per class is generally higher for groups of enzymes that metabolize products of oxidative damage. Conclusions 1 Protection against oxidative stress seems to be the major driver of positive selection in mammalian cGSTs, explaining the overall expansion pattern of this subfamily; 2 Given the functional redundancy of GSTs that metabolize xenobiotic chemicals, we would expect the loss of gene duplicates, but by contrast we observed a gene expansion of this family, which likely has been favored by: i the diversification of endogenous substrates; ii differential tissue expression; and iii increased specificity for a particular molecule; 3 The increased availability of sequence data from diversified taxa is likely to continue to improve our understanding of the early origin of the different cGST classes.

  6. Palmitoylation of the Cysteine Residue in the DHHC Motif of a Palmitoyl Transferase Mediates Ca2+ Homeostasis in Aspergillus.

    Directory of Open Access Journals (Sweden)

    Yuanwei Zhang

    2016-04-01

    Full Text Available Finely tuned changes in cytosolic free calcium ([Ca2+]c mediate numerous intracellular functions resulting in the activation or inactivation of a series of target proteins. Palmitoylation is a reversible post-translational modification involved in membrane protein trafficking between membranes and in their functional modulation. However, studies on the relationship between palmitoylation and calcium signaling have been limited. Here, we demonstrate that the yeast palmitoyl transferase ScAkr1p homolog, AkrA in Aspergillus nidulans, regulates [Ca2+]c homeostasis. Deletion of akrA showed marked defects in hyphal growth and conidiation under low calcium conditions which were similar to the effects of deleting components of the high-affinity calcium uptake system (HACS. The [Ca2+]c dynamics in living cells expressing the calcium reporter aequorin in different akrA mutant backgrounds were defective in their [Ca2+]c responses to high extracellular Ca2+ stress or drugs that cause ER or plasma membrane stress. All of these effects on the [Ca2+]c responses mediated by AkrA were closely associated with the cysteine residue of the AkrA DHHC motif, which is required for palmitoylation by AkrA. Using the acyl-biotin exchange chemistry assay combined with proteomic mass spectrometry, we identified protein substrates palmitoylated by AkrA including two new putative P-type ATPases (Pmc1 and Spf1 homologs, a putative proton V-type proton ATPase (Vma5 homolog and three putative proteins in A. nidulans, the transcripts of which have previously been shown to be induced by extracellular calcium stress in a CrzA-dependent manner. Thus, our findings provide strong evidence that the AkrA protein regulates [Ca2+]c homeostasis by palmitoylating these protein candidates and give new insights the role of palmitoylation in the regulation of calcium-mediated responses to extracellular, ER or plasma membrane stress.

  7. Genetic polymorphisms in glutathione S-transferase (GST) superfamily and arsenic metabolism in residents of the Red River Delta, Vietnam

    International Nuclear Information System (INIS)

    Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Tu Binh Minh; Pham Thi Kim Trang; Pham Hung Viet; Tanabe, Shinsuke

    2010-01-01

    To elucidate the role of genetic factors in arsenic metabolism, we investigated associations of genetic polymorphisms in the members of glutathione S-transferase (GST) superfamily with the arsenic concentrations in hair and urine, and urinary arsenic profile in residents in the Red River Delta, Vietnam. Genotyping was conducted for GST ω1 (GSTO1) Ala140Asp, Glu155del, Glu208Lys, Thr217Asn, and Ala236Val, GST ω2 (GSTO2) Asn142Asp, GST π1 (GSTP1) Ile105Val, GST μ1 (GSTM1) wild/null, and GST θ1 (GSTT1) wild/null. There were no mutation alleles for GSTO1 Glu208Lys, Thr217Asn, and Ala236Val in this population. GSTO1 Glu155del hetero type showed higher urinary concentration of As V than the wild homo type. Higher percentage of DMA V in urine of GSTM1 wild type was observed compared with that of the null type. Strong correlations between GSTP1 Ile105Val and arsenic exposure level and profile were observed in this study. Especially, heterozygote of GSTP1 Ile105Val had a higher metabolic capacity from inorganic arsenic to monomethyl arsenic, while the opposite trend was observed for ability of metabolism from As V to As III . Furthermore, other factors including sex, age, body mass index, arsenic level in drinking water, and genotypes of As (+ 3 oxidation state) methyltransferase (AS3MT) were also significantly co-associated with arsenic level and profile in the Vietnamese. To our knowledge, this is the first study indicating the associations of genetic factors of GST superfamily with arsenic metabolism in a Vietnamese population.

  8. A novel biomarker for marine environmental pollution of pi-class glutathione S-transferase from Mytilus coruscus.

    Science.gov (United States)

    Liu, Huihui; He, Jianyu; Zhao, Rongtao; Chi, Changfeng; Bao, Yongbo

    2015-08-01

    Glutathione S-transferases (GSTs) are the superfamily of phase II detoxification enzymes that play crucial roles in innate immunity. In this study, a pi-class GST homolog was identified from Mytilus coruscus (named as McGST1, KC525103). The full-length cDNA sequence of McGST1 was 621bp with a 5' untranslated region (UTR) of 70bp and a 3'-UTR of 201bp. The deduced amino acid sequence was 206 residues in length with theoretical pI/MW of 5.60/23.72kDa, containing the conserved G-site and diversiform H-site. BLASTn analysis and phylogenetic relationship strongly suggested that this cDNA sequence was a member of pi class GST family. The prediction of secondary structure displayed a preserved N-terminal and a C-terminal comprised with α-helixes. Quantitative real time RT-PCR showed that constitutive expression of McGST1 was occurred, with increasing order in mantle, muscle, gill, hemocyte, gonad and hepatopancreas. The stimulation of bacterial infection, heavy metals and 180CST could up-regulate McGST1 mRNA expression in hepatopancreas with time-dependent manners. The maximum expression appeared at 6h after pathogenic bacteria injected, with 10-fold in Vibrio alginolyticus and 16-fold in Vibrio harveyi higher than that of the control. The highest point of McGST1 mRNA appeared at different time for exposure to copper (10-fold at day 15), cadmium (9-fold at day10) and 180 CST (10-fold at day 15). These results suggested that McGST1 played a significant role in antioxidation and might potentially be used as indicators and biomarkers for detection of marine environmental pollution. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. O-GlcNAc site-mapping of liver X receptor-α and O-GlcNAc transferase.

    Science.gov (United States)

    Fan, Qiong; Moen, Anders; Anonsen, Jan Haug; Bindesbøll, Christian; Sæther, Thomas; Carlson, Cathrine Rein; Grønning-Wang, Line M

    2018-05-05

    The Liver X Receptor α (LXRα) belongs to the nuclear receptor superfamily and plays an essential role in regulating cholesterol, lipid and glucose metabolism and inflammatory responses. We have previously shown that LXRα is post-translationally modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) with increased transcriptional activity. Moreover, we showed that LXRα associates with O-GlcNAc transferase (OGT) in vitro and in vivo in mouse liver. In this study, we report that human LXRα is O-GlcNAc modified in its N-terminal domain (NTD) by identifying a specific O-GlcNAc site S49 and a novel O-GlcNAc modified peptide 20 LWKPGAQDASSQAQGGSSCILRE 42 . However, O-GlcNAc site-mutations did not modulate LXRα transactivation of selected target gene promoters in vitro. Peptide array and co-immunoprecipitation assays demonstrate that LXRα interacts with OGT in its NTD and ligand-binding domain (LBD) in a ligand-independent fashion. Moreover, we map two new O-GlcNAc sites in the longest OGT isoform (ncOGT): S437 in the tetratricopeptide repeat (TPR) 13 domain and T1043 in the far C-terminus, and a new O-GlcNAc modified peptide (amino acids 826-832) in the intervening region (Int-D) within the catalytic domain. We also map four new O-GlcNAc sites in the short isoform sOGT: S391, T393, S399 and S437 in the TPRs 11-13 domain. Future studies will reveal the biological role of identified O-GlcNAc sites in LXRα and OGT. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity.

    Science.gov (United States)

    Shi, Hao; Munk, Alexander; Nielsen, Thomas S; Daughtry, Morgan R; Larsson, Louise; Li, Shize; Høyer, Kasper F; Geisler, Hannah W; Sulek, Karolina; Kjøbsted, Rasmus; Fisher, Taylor; Andersen, Marianne M; Shen, Zhengxing; Hansen, Ulrik K; England, Eric M; Cheng, Zhiyong; Højlund, Kurt; Wojtaszewski, Jørgen F P; Yang, Xiaoyong; Hulver, Matthew W; Helm, Richard F; Treebak, Jonas T; Gerrard, David E

    2018-05-01

    Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2). Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

  11. Glutathione S-transferases in human renal cortex and neoplastic tissue: enzymatic activity, isoenzyme profile and immunohistochemical localization.

    Science.gov (United States)

    Rodilla, V; Benzie, A A; Veitch, J M; Murray, G I; Rowe, J D; Hawksworth, G M

    1998-05-01

    1. Glutathione S-transferase (GST) activity in the cytosol of renal cortex and tumours from eight men and eight women was measured using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. GST activities ranged from 685 to 2192 nmol/min/mg protein in cortex (median 1213) and from non-detectable (minimum 45) to 2424 nmol/min/mg protein in tumours (median 469). The activities in the tumours were lower than those in the normal cortices (p 0.05). 3. The age of the patients ranged from 42 to 81 years (median 62) and was not found to play a role in the levels of GST activity observed in cortex or in renal tumours from either sex. 4. Immunoblotting and immunohistochemical studies confirmed that GST-alpha was the predominant form expressed both in normal cortex and tumour and probably accounted for most of the GST activity present in these samples. GST-mu and GST-phi were expressed in both tumours and normal cortex and, while in some cases the level of expression in the cortices was higher than that found in the tumours, the reverse was also observed. Within the GST-mu class, GST M1/M2 was only detected in one sample (tumour), which showed the highest overall expression of GST-mu. GSTM3 was the predominant isoenzyme of the mu class in normal and tumour tissue, whereas GTM4 and GSTM5 were not detected. 5. These differences could have functional significance where xenobiotics or cytotoxic drugs are specific substrates for the different classes of GSTs.

  12. Oral health in frail elderly

    NARCIS (Netherlands)

    Hoeksema, Albert

    2016-01-01

    Ageing points towards increasing health problems and rising costs for the society. One of these health problems is the deteriorating oral health in care dependent elderly. The latter is related to the high need for care on many levels in these elderly. The lack of attention for oral care can be

  13. Oral health problems and mortality

    Directory of Open Access Journals (Sweden)

    Jung Ki Kim

    2013-06-01

    Conclusion: Individual oral health conditions—tooth loss, root caries, and periodontal disease—were not related to mortality when sociodemographic, health, and/or health behavioral factors were considered, and there was no differential pattern between the three conditions. Multiple oral health problems were associated with a higher risk of dying.

  14. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... be diagnosed with oral or pharyngeal cancer this year. Here’s what you need to know. Click here ... be diagnosed with oral or pharyngeal cancer this year. Here’s what you need to know. Click here ...

  15. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... will be diagnosed with oral or pharyngeal cancer this year. Here’s what you need to know. Click here ... will be diagnosed with oral or pharyngeal cancer this year. Here’s what you need to know. Click here ...

  16. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... the cancer is often discovered late in its development. Your family dentist or OMS is in the best position to detect oral cancer during your routine dental examinations. Don't risk it. Perform an oral cancer self-exam each month. Perform a Self-Exam Monthly ...

  17. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Americans will be diagnosed with oral or pharyngeal cancer this year. Here’s what you need to know. ... Americans will be diagnosed with oral or pharyngeal cancer this year. Here’s what you need to know. ...

  18. BETTER ORAL HEALTH TO ALL

    Directory of Open Access Journals (Sweden)

    Heikki Murtomaa

    2016-12-01

    The behavioral science experts are of opinion that only comprehensive and integrated common-risk-factor-based health promotion activities can enhance oral health and its equity as a part of general health. Are health professionals ready to assume their responsibility for promoting better oral health?

  19. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral, Head and Neck Pathology TMJ and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons are ... more. TMJ and Facial Pain TMJ and Facial ... Teeth Management Wisdom Teeth Management An impacted wisdom tooth can ...

  20. Scandinavian Fellowship for Oral Pathology and Oral Medicine: statement on oral pathology and oral medicine in the European Dental Curriculum

    DEFF Research Database (Denmark)

    Kragelund, C; Reibel, J; Hadler-Olsen, E S

    2010-01-01

    source in revisions of dental curricula throughout Europe converging towards a European Dental Curriculum. In order to render the best conditions for future curriculum revisions providing the best quality dentist we feel obliged to analyse and comment the outlines of oral pathology and oral medicine...

  1. [Drug-induced oral ulcerations].

    Science.gov (United States)

    Madinier, I; Berry, N; Chichmanian, R M

    2000-06-01

    Different side effects of drugs have been described in the oral cavity, including oral ulcerations. Direct contact between drugs and oral mucosa may induce chemical burn or local hypersensitivity. Less frequently, these drug-induced oral ulcerations are part of a complex reaction with cutaneous or systemic manifestations. Sometimes, one or more oral ulcerations appear as the main side-effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations usually appear after few weeks of treatment. In most of cases, these lesions resist to conventional treatments, with a rapid healing following the suppression of the responsible drug. This diagnosis is usually difficult, particularly with patients receiving multiple drug therapy. Besides, special attention must be paid to new drugs. Oral ulcerations following symptoms of burning mouth, metallic taste, dysgueusia or agueusia are strongly suggestive of a pharmacological origin. Most of the molecules able to induce solitary oral ulcerations are commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen, indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine, methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology: angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2-receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry: antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

  2. The Oral Paradigm and Snapchat

    Directory of Open Access Journals (Sweden)

    Oren Soffer

    2016-09-01

    Full Text Available In this short essay, I argue that the ephemeral nature of emerging instant-messaging applications, such as Snapchat, applies an oral paradigm. While online discourse of computer-mediated communication shares many qualities with oral communication, the case of ephemeral applications is unique, as the oral features are already integrated in the application technology design and as orality is often implemented on highly visual products. Snapchat applies technology that fades visual contents as if they were spoken words fading in the air after utterance. Moreover, Snapchat’s promise to delete all messages from its database after they are viewed echoes a key characteristic of primary oral culture: that is, the inability (and in our case, the obligation not to store knowledge. In this, Snapchat demonstrates counter-logic to the contemporary grammar of new media, which is based on information aggregation.

  3. Direct oral anticoagulants: An update.

    Science.gov (United States)

    Franco Moreno, Ana Isabel; Martín Díaz, Rosa María; García Navarro, María José

    2017-12-30

    Vitamin K antagonists were the only choice for chronic oral anticoagulation for more than half a century. Over the past few years, direct oral anticoagulants have emerged, including one direct thrombin inhibitor (dabigatran etexilate) and three factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). In randomised controlled trials comparing direct oral anticoagulants with traditional vitamin K antagonists, the direct oral anticoagulants all showed a favourable benefit-risk balance in their safety and efficacy profile, in prevention of thromboembolic events in patients with atrial fibrillation and in the prevention and treatment of venous thromboembolism and acute coronary syndrome. In 2008, dabigatran was the first direct oral anticoagulant approved by the European Medicine Agency. Subsequently, rivaroxaban, apixaban and edoxaban were also authorised. This article reviews the evidence related to the use of these drugs. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  4. Oral candidiasis and angular cheilitis.

    Science.gov (United States)

    Sharon, Victoria; Fazel, Nasim

    2010-01-01

    Candidiasis, an often encountered oral disease, has been increasing in frequency. Most commonly caused by the overgrowth of Candida albicans, oral candidiasis can be divided into several categories including acute and chronic forms, and angular cheilitis. Risk factors for the development of oral candidiasis include immunosuppression, wearing of dentures, pharmacotherapeutics, smoking, infancy and old age, endocrine dysfunction, and decreased salivation. Oral candidiasis may be asymptomatic. More frequently, however, it is physically uncomfortable, and the patient may complain of burning mouth, dysgeusia, dysphagia, anorexia, and weight loss, leading to nutritional deficiency and impaired quality of life. A plethora of antifungal treatments are available. The overall prognosis of oral candidiasis is good, and rarely is the condition life threatening with invasive or recalcitrant disease.

  5. Oral epithelial dysplasia classification systems

    DEFF Research Database (Denmark)

    Warnakulasuriya, S; Reibel, J; Bouquot, J

    2008-01-01

    At a workshop coordinated by the WHO Collaborating Centre for Oral Cancer and Precancer in the United Kingdom issues related to potentially malignant disorders of the oral cavity were discussed by an expert group. The consensus views of the Working Group are presented in a series of papers....... In this report, we review the oral epithelial dysplasia classification systems. The three classification schemes [oral epithelial dysplasia scoring system, squamous intraepithelial neoplasia and Ljubljana classification] were presented and the Working Group recommended epithelial dysplasia grading for routine...... use. Although most oral pathologists possibly recognize and accept the criteria for grading epithelial dysplasia, firstly based on architectural features and then of cytology, there is great variability in their interpretation of the presence, degree and significance of the individual criteria...

  6. Oral Pathology in Forensic Investigation.

    Science.gov (United States)

    Shamim, Thorakkal

    2018-01-01

    Forensic odontology is the subdiscipline of dentistry which analyses dental evidence in the interest of justice. Oral pathology is the subdiscipline of dentistry that deals with the pathology affecting the oral and maxillofacial regions. This subdiscipline is utilized for identification through oral and maxillofacial pathologies with associated syndromes, enamel rod patterns, sex determination using exfoliative cytology, identification from occlusal morphology of teeth, and deoxyribonucleic acid profiling from teeth. This subdiscipline is also utilized for age estimation studies which include Gustafson's method, incremental lines of Retzius, perikymata, natal line formation in teeth, neonatal line, racemization of collagen in dentin, cemental incremental lines, thickness of the cementum, and translucency of dentin. Even though the expertise of an oral pathologist is not taken in forensic investigations, this paper aims to discuss the role of oral pathology in forensic investigation.

  7. Oral lichen planus: An overview

    Directory of Open Access Journals (Sweden)

    R Jayasri Krupaa

    2015-01-01

    Full Text Available Lichen planus is an immunologically mediated mucocutaneous disease that is triggered by varied etiological agents. The oral lichenoid reaction is considered a variant of the disease that needs to be clearly diagnosed as a separate entity from oral lichen planus and treated. They follow a strict cause-effector relationship, protocols that suggest the differentiation. Lichen planus has varied clinical forms in the oral mucosa and cutaneously that has different prognosis. This condition also arises in association with various other systemic conditions such as hypertension, diabetes mellitus. There have been cases reported in the esophagus, larynx, scalp, nail, cutaneous areas, especially arms and wrists, trunk. There is reported malignant transformation that essentiates careful examination, treatment protocol and regular follow-up sessions. This article throws light on the disease condition of oral lichen planus and oral lichenoid reaction that is essential for the differentiation and treatment.

  8. Oral lichen planus: An overview

    Science.gov (United States)

    Krupaa, R. Jayasri; Sankari, S. Leena; Masthan, K. M. K.; Rajesh, E.

    2015-01-01

    Lichen planus is an immunologically mediated mucocutaneous disease that is triggered by varied etiological agents. The oral lichenoid reaction is considered a variant of the disease that needs to be clearly diagnosed as a separate entity from oral lichen planus and treated. They follow a strict cause-effector relationship, protocols that suggest the differentiation. Lichen planus has varied clinical forms in the oral mucosa and cutaneously that has different prognosis. This condition also arises in association with various other systemic conditions such as hypertension, diabetes mellitus. There have been cases reported in the esophagus, larynx, scalp, nail, cutaneous areas, especially arms and wrists, trunk. There is reported malignant transformation that essentiates careful examination, treatment protocol and regular follow-up sessions. This article throws light on the disease condition of oral lichen planus and oral lichenoid reaction that is essential for the differentiation and treatment. PMID:26015696

  9. Why Is Oral Health Important for Women?

    Science.gov (United States)

    ... 2018 About | Contact InfoBites Quick Reference Learn more Oral Health and Overal Health Gum Disease and Cardiovascular Health ... delivered directly to your desktop! more... Why Is Oral Health Important for Women? Article Chapters Why Is Oral ...

  10. Pregnancy Cravings Can Harm Your Oral Health

    Science.gov (United States)

    ... 2018 About | Contact InfoBites Quick Reference Learn more Oral Health and Overal Health Gum Disease and Cardiovascular Health ... your desktop! more... Pregnancy Cravings Can Harm Your Oral Health Article Chapters Pregnancy Cravings Can Harm Your Oral ...

  11. The Fungal Biome of the Oral Cavity.

    Science.gov (United States)

    Chandra, Jyotsna; Retuerto, Mauricio; Mukherjee, Pranab K; Ghannoum, Mahmoud

    2016-01-01

    Organisms residing in the oral cavity (oral microbiota) contribute to health and disease, and influence diseases like gingivitis, periodontitis, and oral candidiasis (the most common oral complication of HIV-infection). These organisms are also associated with cancer and other systemic diseases including upper respiratory infections. There is limited knowledge regarding how oral microbes interact together and influence the host immune system. Characterizing the oral microbial community (oral microbiota) in health and disease represents a critical step in gaining insight into various members of this community. While most of the studies characterizing oral microbiota have focused on bacterial community, there are few encouraging studies characterizing the oral mycobiome (the fungal component of the oral microbiota). Our group recently characterized the oral mycobiome in health and disease focusing on HIV. In this chapter we will describe the methods used by our group for characterization of the oral mycobiome.

  12. Need for Oral Health Policy in India

    African Journals Online (AJOL)

    implementation of National Oral Health Policy in India in order to expand the oral health care to ... Professional dental organizations can also support government programs to .... who can play effective role in providing oral health care services.

  13. Oral candidiasis following steroid therapy for oral lichen planus.

    Science.gov (United States)

    Marable, D R; Bowers, L M; Stout, T L; Stewart, C M; Berg, K M; Sankar, V; DeRossi, S S; Thoppay, J R; Brennan, M T

    2016-03-01

    The purpose of this multicentre study was to determine the incidence of oral candidiasis in patients treated with topical steroids for oral lichen planus (OLP) and to determine whether the application of a concurrent antifungal therapy prevented the development of an oral candidiasis in these patients. Records of 315 patients with OLP seen at four Oral Medicine practices treated for at least 2 weeks with steroids with and without the use of an antifungal regimen were retrospectively reviewed. The overall incidence of oral fungal infection in those treated with steroid therapy for OLP was 13.6%. There was no statistically significant difference in the rate of oral candidiasis development in those treated with an antifungal regimen vs those not treated prophylactically (14.3% vs 12.6%) (P = 0.68). Despite the use of various regimens, none of the preventive antifungal strategies used in this study resulted in a significant difference in the rate of development of an oral candidiasis in patients with OLP treated with steroids. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Nutrition and Oral Health: Experiences in Iran

    OpenAIRE

    Zohre Sadat Sangsefidi; Amin Salehi-Abargouei

    2017-01-01

    Background: Oral health is a crucial factor for overall well-being and there is a mutual relationship between nutrition and oral health. The aim of this study was to review the publications which have examined the association between nutrition or diet and oral health status or oral disease in Iran. Methods: The electronic databases of PubMed, Scopus, Google scholar, scientific information database (SID), and Magiran were searched using key words of diet, nutrition, oral health, oral disease, ...

  15. The oral microbiome - an update for oral healthcare professionals

    DEFF Research Database (Denmark)

    Kilian, M; Chapple, I L C; Hannig, M

    2016-01-01

    disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current...... and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral...

  16. Oral cancer: A multicenter study

    Science.gov (United States)

    Rojanawatsirivej, Somsri; Thosaporn, Watcharaporn; Kintarak, Sompid; Subarnbhesaj, Ajiravudh; Darling, Mark; Kryshtalskyj, Eugene; Chiang, Chun-Pin; Shin, Hong-In; Choi, So-Young; Lee, Sang-shin; Shakib, Pouyan-Amini

    2018-01-01

    Background To determine the prevalence and clinicopathologic features of the oral cancer patients. Material and Methods Biopsy records of the participating institutions were reviewed for oral cancer cases diagnosed from 2005 to 2014. Demographic data and site of the lesions were collected. Sites of the lesion were subdivided into lip, tongue, floor of the mouth, gingiva, alveolar mucosa, palate, buccal/labial mucosa, maxilla and mandible. Oral cancer was subdivided into 7 categories: epithelial tumors, salivary gland tumors, hematologic tumors, bone tumors, mesenchymal tumors, odontogenic tumors, and others. Data were analyzed by descriptive statistics using SPSS software version 17.0. Results Of the 474,851 accessioned cases, 6,151 cases (1.30%) were diagnosed in the category of oral cancer. The mean age of the patients was 58.37±15.77 years. A total of 4,238 cases (68.90%) were diagnosed in males, whereas 1911 cases (31.07%) were diagnosed in females. The male-to-female ratio was 2.22:1. The sites of predilection for oral cancer were tongue, labial/buccal mucosa, gingiva, palate, and alveolar mucosa, respectively. The three most common oral cancer in the descending order of frequency were squamous cell carcinoma, non-Hodgkin lymphoma and mucoepidermoid carcinoma. Conclusions Although the prevalence of oral cancer is not high compared to other entities, oral cancer pose significant mortality and morbidity in the patients, especially when discovered late in the course of the disease. This study highlights some anatomical locations where oral cancers are frequently encountered. As a result, clinicians should pay attention to not only teeth, but oral mucosa especially in the high prevalence area as well since early detection of precancerous lesions or cancers in the early stage increase the chance of patient being cured and greatly reduce the mortality and morbidity. This study also shows some differences between pediatric and elderly oral cancer patients as well as

  17. Oral symptoms and salivary findings in oral lichen planus, oral lichenoid lesions and stomatitis

    DEFF Research Database (Denmark)

    Larsen, Kristine Roen; Johansen, Jeanne Duus; Reibel, Jesper

    2017-01-01

    BACKGROUND: To examine if patients with oral lichen planus, oral lichenoid lesions and generalised stomatitis and concomitant contact allergy have more frequent and severe xerostomia, lower unstimulated and chewing-stimulated saliva and citric-acid-stimulated parotid saliva flow rates, and higher...... of xerostomia, clinical examination, sialometry, mucosal biopsy and contact allergy testing. RESULTS: Nineteen patients had oral lichen planus, 19 patients had oral lichenoid lesions and 11 patients had generalised stomatitis. 38.8% had contact allergy. Xerostomia was significantly more common and severe...... in the chewing stimulated saliva samples from patients when compared to healthy controls. The differences were not significant and they were irrespective of the presence of contact allergy. CONCLUSION: Xerostomia is prevalent in patients with oral lichen planus, lichenoid lesions and generalised stomatitis...

  18. Amiloidosis bucal Oral amyloidosis

    Directory of Open Access Journals (Sweden)

    Isabella Lima Arrais Ribeiro

    2012-03-01

    Full Text Available A amiloidose é uma doença complexa rara de difícil diagnóstico que ocorre devido à deposição de substância amilóide no meio extracelular. Ao ser diagnosticado na cavidade bucal, deve-se monitorar o paciente a fim de avaliar possíveis complicações sistêmicas da doença. Diante disso, o objetivo do presente estudo é relatar um caso de amiloidose oral em uma paciente do gênero feminino de 72 anos de idade. Baseado nos sinais clínicos observados, a hipótese diagnóstica foi de fibroma traumático. Após realização de biópsia e exame histopatológico, o diagnóstico foi de amiloidose oral, o que foi confirmado com a coloração do espécime com o reagente vermelho congo. Depósitos de amilóide foram encontrados no tecido conjuntivo, na avaliação através da luz polarizada, que apresentou birrefringência. Tal achado foi preocupante, já que a amiloidose geralmente acomete diversos tecidos levando a comprometimentos sistêmicos. Por essa razão a paciente foi encaminhada a procurar atendimento médico. No entanto, houve abandono do tratamento e a mesma veio a óbito 6 meses após o diagnóstico da doença. Lesões orais aparentemente simples podem revelar doenças raras e de difícil tratamento. O diagnóstico preciso e acompanhamentos médicos são fundamentais na sobrevida do paciente.La amiloidosis es una enfermedad compleja, rara, de difícil diagnóstico, que ocurre debido al depósito de sustancia amiloidea en medio extracelular. Al ser diagnosticada en la cavidad bucal, el paciente debe tener supervisión médica para evaluar las posibles complicaciones sistémicas de la enfermedad. El objetivo del presente estudio fue presentar un caso de amiloidosis bucal en un paciente del género femenino de 72 años de edad. Basados en las señales clínicas observadas, la hipótesis diagnóstica fue de un fibroma traumático. Después de la realización de una biopsia y del examen histopatológico, el diagnóstico fue de amiloidosis

  19. Criteria for Evaluating Oral History Interviews.

    Science.gov (United States)

    Fonsino, Frank J.

    1980-01-01

    Discusses the rationale for establishing criteria for evaluating oral history interviews. Presents seven evaluation categories relating to oral history tapes and three categories relating to typescripts. (CK)

  20. Genetic etiology of oral cancer.

    Science.gov (United States)

    Ali, Johar; Sabiha, Bibi; Jan, Hanif Ullah; Haider, Syed Adnan; Khan, Abid Ali; Ali, Saima S

    2017-07-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. More than 90% of oral cancers (occurring in the mouth, lip, and tongue) are oral squamous cell carcinoma. The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. This high incidence occurs in correlation with oral cancer-associated behaviors such as alcohol, tobacco use. Researchers have reported that these behaviors lead to genetic variations in tumor suppressor genes (APC, p53), proto-oncogenes (Myc), oncogene (Ras) and genes controlling normal cellular processes (EIF3E, GSTM1). Processes such as segregation of chromosomes, genomic copy number, loss of heterozygosity, telomere stabilities, regulations of cell-cycle checkpoints, DNA damage repairs and defects in notch signaling pathways are involved in causing oral cancer. In order to develop preventive and therapeutic options, it is necessary to comprehend the basic molecular mechanisms forcing oral tumorigenesis. This review examines, in detail, the mechanisms of genetic alteration which are considered to be responsible for the initiation of oral cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. ORAL HYGIENE PRACTICES AND RISK OF ORAL LEUKOPLAKIA

    African Journals Online (AJOL)

    2006-04-01

    Apr 1, 2006 ... EAST AFRICAN MEDICAL JOURNAL ... Faculty of Dental Sciences, University of Nairobi, P.O. Box 19676 - 00202, Nairobi, ... Poor oral hygiene is a product of plaque and ..... University of Nairobi and Kenya Medical Research.

  2. Oral hygiene and oral flora evaluation in psychiatric patients in ...

    African Journals Online (AJOL)

    2015-03-02

    Mar 2, 2015 ... Key words: Bacteria types, oral and dental illnesses, psychiatric patients. Date of Acceptance: .... patients, and difficulties such as insufficient sedation.[7]. This study .... Despite the general notion that stress triggers bruxism ...

  3. Oral lichen planus to oral lichenoid lesions: Evolution or revolution

    Science.gov (United States)

    Dudhia, Bhavin B; Dudhia, Sonal B; Patel, Purv S; Jani, Yesha V

    2015-01-01

    The diagnosis between different diseases may be impaired by clinical and histopathologic similarities, as observed in the oral lichen planus (OLP) and oral lichenoid lesion (OLL). Inspite of similar clinicopathological features; etiology, diagnosis and prognosis differ which mandates separation of OLL from OLP. Hence, it is essential for the oral physician and oral pathologist to be familiarized with the individual variations among clinicopathological features of OLP and OLL as well as to obtain a thorough history and perform a complete mucocutaneous examination in addition to specific diagnostic testing. The difficulties faced to establish the diagnosis between these two pathologies are widely investigated in the literature with a lack of definite conclusion. This review is an attempt to throw some light on these clinicopathologic entities with the aim to resolve the diagnostic dilemma. PMID:26980966

  4. Epoxyalkane:Coenzyme M Transferase Gene Diversity and Distribution in Groundwater Samples from Chlorinated-Ethene-Contaminated Sites

    Science.gov (United States)

    Liu, Xikun

    2016-01-01

    ABSTRACT Epoxyalkane:coenzyme M transferase (EaCoMT) plays a critical role in the aerobic biodegradation and assimilation of alkenes, including ethene, propene, and the toxic chloroethene vinyl chloride (VC). To improve our understanding of the diversity and distribution of EaCoMT genes in the environment, novel EaCoMT-specific terminal-restriction fragment length polymorphism (T-RFLP) and nested-PCR methods were developed and applied to groundwater samples from six different contaminated sites. T-RFLP analysis revealed 192 different EaCoMT T-RFs. Using clone libraries, we retrieved 139 EaCoMT gene sequences from these samples. Phylogenetic analysis revealed that a majority of the sequences (78.4%) grouped with EaCoMT genes found in VC- and ethene-assimilating Mycobacterium strains and Nocardioides sp. strain JS614. The four most-abundant T-RFs were also matched with EaCoMT clone sequences related to Mycobacterium and Nocardioides strains. The remaining EaCoMT sequences clustered within two emergent EaCoMT gene subgroups represented by sequences found in propene-assimilating Gordonia rubripertincta strain B-276 and Xanthobacter autotrophicus strain Py2. EaCoMT gene abundance was positively correlated with VC and ethene concentrations at the sites studied. IMPORTANCE The EaCoMT gene plays a critical role in assimilation of short-chain alkenes, such as ethene, VC, and propene. An improved understanding of EaCoMT gene diversity and distribution is significant to the field of bioremediation in several ways. The expansion of the EaCoMT gene database and identification of incorrectly annotated EaCoMT genes currently in the database will facilitate improved design of environmental molecular diagnostic tools and high-throughput sequencing approaches for future bioremediation studies. Our results further suggest that potentially significant aerobic VC degraders in the environment are not well represented in pure culture. Future research should aim to isolate and

  5. Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling.

    Science.gov (United States)

    Singhal, Sharad S; Singh, Sharda P; Singhal, Preeti; Horne, David; Singhal, Jyotsana; Awasthi, Sanjay

    2015-12-15

    4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes - higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article. Copyright © 2015 Elsevier Inc. All rights

  6. Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Hao Shi

    2018-05-01

    Full Text Available Objective: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT, the enzyme that mediates O-GlcNAcylation, in skeletal muscle. Methods: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. Results: We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2. Conclusions: Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. Keywords: O-GlcNAc signaling, Type 2 diabetes, N

  7. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

    International Nuclear Information System (INIS)

    Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick

    1999-01-01

    Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

  8. Gene polymorphisms of glutathione S-transferase omega 1 and 2, urinary arsenic methylation profile and urothelial carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Huang, Chao-Yuan [Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2011-01-01

    Genetic polymorphisms in arsenic-metabolizing enzymes may be involved in the biotransformation of inorganic arsenic and may increase the risk of developing urothelial carcinoma (UC). The present study evaluated the roles of glutathione S-transferase omega 1 (GSTO1) and GSTO2 polymorphisms in UC carcinogenesis. A hospital-based case-control study was conducted. Questionnaire information and biological specimens were collected from 149 UC cases and 251 healthy controls in a non-obvious inorganic arsenic exposure area in Taipei, Taiwan. The urinary arsenic profile was determined using high-performance liquid chromatography and hydride generator-atomic absorption spectrometry. Genotyping for GSTO1 Ala140Asp and GSTO2 Asn142Asp was conducted using polymerase chain reaction-restriction fragment length polymerase. GSTO1 Glu208Lys genotyping was performed using high-throughput matrix-assisted laser desorption and ionization time-of-flight mass spectrometry. A significant positive association was found between total arsenic, inorganic arsenic percentage and monomethylarsonic acid percentage and UC, while dimethylarsinic acid percentage was significantly inversely associated with UC. The minor allele frequency of GSTO1 Ala140Asp, GSTO1 Glu208Lys and GSTO2 Asn142Asp was 18%, 1% and 26%, respectively. A significantly higher MMA% was found in people who carried the wild type of GSTO1 140 Ala/Ala compared to those who carried the GSTO1 140 Ala/Asp and Asp/Asp genotype (p = 0.02). The homogenous variant genotype of GSTO2 142 Asp/Asp was inversely associated with UC risk (OR = 0.17; 95% CI, 0.03 - 0.88; p = 0.03). Large-scale studies will be required to verify the association between the single nucleotide polymorphisms of arsenic-metabolism-related enzymes and UC risk. - Research Highlights: {yields} The homogenous variant genotype of GSTO2 was inversely associated with UC risk. {yields} A higher urinary MMA% was found in people carrying the wild type of GSTO1 Ala140Asp. {yields

  9. Association between glutathione S-transferase M1 and T1 polymorphisms and colorectal cancer risk in patients from Kazakhstan.

    Science.gov (United States)

    Zhunussova, Gulnur; Zhunusbekova, Benazir; Djansugurova, Leyla

    2015-01-01

    Colorectal cancer (CRC) is one of the most common malignancies worldwide and the incidence is increasing in developed as well as developing countries including Kazakhstan. Glutathione S-transferases (GSTs) are considered to be cancer susceptibility genes as they play a role in the detoxification of carcinogenic species. In this case-control study the influence of GSTM1 and GSTT1 polymorphisms on CRC risk in Kazakhstan population were evaluated. Blood samples were collected from patients diagnosed with rectal or colon cancer (300 individuals) as well as a control cohort of healthy volunteers (300 individuals), taking into account the age, gender, ethnicity, and smoking habits of the CRC patients. Deletion polymorphisms were genotyped employing a multiplex PCR amplification method. Association between polymorphisms and CRC susceptibility risk was calculated using multivariate analysis and logistic regression for odd ratio (OR). The homozygous GSTM1 null genotype was associated with significantly increased risk of CRC (OR = 2.01, 95% CI = 1.45-2.79, p = 0.0001) while the homozygous GSST1 null genotype was not associated with the risk of developing CRC (OR = 1.10, 95% CI = 0.78-1.55, p = 0.001), but the heterozygous genotype correlated with CRC susceptibility (OR = 1.98, 95% CI = 1.30-3.00, p = 0.001). Also, separate analyses of each of the main ethnic groups (Kazakh and Russian) showed a strong association of GSTM1 null genotype with CRC risk (for Kazakhs OR = 2.36, 95% CI = 1.35-4.10, p = 0.006 and for Russians OR = 1.84, 95% CI = 1.17-2.89, p = 0.003). The CRC risk of GSTM1 null genotype in smokers was considerably higher (OR = 3.37, 95% CI = 1.78-6.38, p = 0.0007). The combination of the GSTM1 and GSTT1 null genotypes in combined mixed population of Kazakhstan showed a trend to increasing the risk of developing CRC (OR = 1.60, 95% CI = 1.00-2.56), but it was not statistically significant. In conclusion, the results of this case-control study for sporadic cases of

  10. Pattern of γ-glutamyl transferase activity in cow milk throughout lactation and relationships with metabolic conditions and milk composition.

    Science.gov (United States)

    Calamari, L; Gobbi, L; Russo, F; Cappelli, F Piccioli

    2015-08-01

    The main objective of this experiment was to study the γ-glutamyl transferase (GGT) activity in milk during lactation and its relationship with metabolic status of dairy cows, milk yield, milk composition, and cheesemaking properties. The study was performed in a tied stall barn and involved 20 lactations from 12 healthy multiparous Italian Friesian dairy cows. During lactation starting at d 10, milk samples were collected weekly and analyzed for composition, somatic cells count, titratable acidity, and milk coagulation properties. The GGT activity was measured in defatted samples. Blood samples were collected weekly to assess biochemical indicators related to energy, protein, and mineral metabolism, markers of inflammation and some enzyme activities. The lactations of each cow were retrospectively categorized into 2 groups according to their milk GGT activity value through lactation. A median value of GGT activity in the milk of all lactations was calculated (3,045 U/L), and 10 lactations with lower GGT activity were classified as low while 10 lactations with greater GGT activity were classified as high. The average value of milk GGT activity during lactation was 3,863 and 3,024 U/L for high and low, respectively. The GGT activity decreased in early lactation and reached minimum values in the second month (3,289 and 2,355 U/L for high and low, respectively). Thereafter GGT activity increased progressively, reaching values in late lactation of 4,511 and 3,540 U/L in high and low, respectively. On average, milk yield was 40.81 and 42.76 kg/d in high and low, respectively, and a negative partial correlation with milk GGT activity was observed. A greater milk protein concentration was observed in high (3.39%) compared with low (3.18%), and a positive partial correlation with milk GGT activity was observed. Greater titratable acidity in high than that in low (3.75 vs. 3.45 degrees Soxhlet-Henkel/50 mL, respectively) was also observed. Plasma glucose was greater in

  11. Toxicological responses on cytochrome P450 and metabolic transferases in liver of goldfish (Carassius auratus) exposed to lead and paraquat.

    Science.gov (United States)

    Xu, Xiaoming; Cui, Zhaojie; Wang, Xinlei; Wang, Xixin; Zhang, Su

    2018-04-30

    As the producer of reactive oxygen species (ROS), both lead (Pb) and paraquat (PQ) can generate serious oxidative stress in target organs which result in irreversible toxic effects on organisms. They can disturb the normal catalytic activities of many enzymes by means of different toxicity mechanism. The changed responses of enzymes are frequently used as the biomarkers for indicating the relationship between toxicological effects and exposure levels. In this work, goldfish was exposed to a series of test groups containing lead and paraquat in the range of 0.05-10mg/L, respectively. Four hepatic enzyme activities, including 7-ethoxyresorufinO-deethylase (EROD), 7-benzyloxy-4-trifluoromethyl-coumarin-O-debenzyloxylase (BFCOD), glutathione S-transferase (GST) and UDP-glucuronosyltransferase (UGT) were determined after 1, 7, 14, 28 days exposure. The results showed that the activities of EROD and BFCOD in fish were significantly inhibited in response to paraquat at all exposure levels during the whole experiment. Similarly, the inhibitory effects of lead exposure on BFCOD activity were found in our study, while different responses of lead on EROD were observed. There were no significant differences on EROD activity under lower concentrations of lead (less than 0.1mg/L) before 14 days until an obvious increase was occurred for the 0.5mg/L lead treatment group at day 14. Furthermore, lead showed stronger inhibition on GST activity than paraquat when the concentrations of the two toxicants were more than 0.5mg/L. However, the similar dose and time-dependent manners of UGT activity were found under lead and paraquat exposure. Our results indicated that higher exposure levels and longer accumulations caused inhibitory effects on the four enzymes regardless of lead or paraquat stress. In addition, the responses of phase I enzymes were more sensitive than that of phase II enzymes and they may be served as the acceptable biomarkers for evaluating the toxicity effects of both

  12. Glutathione-S-transferase A3 knockout mice are sensitive to acute cytotoxic and genotoxic effects of aflatoxin B1

    International Nuclear Information System (INIS)

    Ilic, Zoran; Crawford, Dana; Egner, Patricia A.; Sell, Stewart

    2010-01-01

    Aflatoxin B1 (AFB1) is a major risk factor for hepatocellular carcinoma (HCC) in humans. However, mice, a major animal model for the study of AFB1 carcinogenesis, are resistant, due to high constitutive expression, in the mouse liver, of glutathione S-transferase A3 subunit (mGSTA3) that is lacking in humans. Our objective was to establish that a mouse model for AFB1 toxicity could be used to study mechanisms of toxicity that are relevant for human disease, i.e., an mGSTA3 knockout (KO) mouse that responds to toxicants such as AFB1 in a manner similar to humans. Exons 3-6 of the mGSTA3 were replaced with a neomycin cassette by homologous recombination. Southern blotting, RT-PCR, Western blotting, and measurement of AFB1-N 7 -DNA adduct formation were used to evaluate the mGSTA3 KO mice. The KO mice have deletion of exons 3-6 of the mGSTA3 gene, as expected, as well as a lack of mGSTA3 expression at the mRNA and protein levels. Three hours after injection of 5 mg/kg AFB1, mGSTA3 KO mice have more than 100-fold more AFB1-N 7 -DNA adducts in their livers than do similarly treated wild-type (WT) mice. In addition, the mGSTA3 KO mice die of massive hepatic necrosis, at AFB1 doses that have minimal toxic effects in WT mice. We conclude that mGSTA3 KO mice are sensitive to the acute cytotoxic and genotoxic effects of AFB1, confirming the crucial role of GSTA3 subunit in protection of normal mice against AFB1 toxicity. We propose the mGSTA3 KO mouse as a useful model with which to study the interplay of risk factors leading to HCC development in humans, as well as for testing of additional possible functions of mGSTA3.

  13. Protective role for ovarian glutathione S-transferase isoform pi during 7,12-dimethylbenz[a]anthracene-induced ovotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharya, Poulomi, E-mail: poulomib@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2012-04-15

    7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all developmental stages. This study investigated a role for the glutathione S-transferase (Gst) isoforms alpha (a), mu (m) and pi (p) and the transcription factors, Ahr and Nrf2, during DMBA-induced ovotoxicity, and their regulation by phosphatidylinositol-3 kinase (PI3K) signaling. Negative regulation of JNK by GSTP during DMBA exposure was also studied. Post-natal day (PND) 4 Fischer 344 rat ovaries were exposed to vehicle control (1% DMSO) ± DMBA (1 μM) or vehicle control (1% DMSO) ± LY294002 (PI3K inhibitor; 20 μM) for 1, 2, 4, or 6 days. Total RNA or protein was isolated, followed by RT-PCR or Western blotting to determine mRNA or protein level, respectively. Immunoprecipitation using an anti-GSTP antibody was performed to determine interaction between GSTP and JNK, followed by Western blotting to determine JNK and p-c-Jun protein level. DMBA had no impact on Gsta, Gstm or Nrf2 mRNA level, but increased Gstp mRNA and protein after 2 days. Ahr mRNA and protein increased after 2 and 4 days of DMBA exposure, respectively and DMBA increased NRF2 protein level after 4 days. JNK bound to GSTP was increased during DMBA exposure, with a concomitant decrease in unbound JNK and p-c-Jun. Ahr and Gstp mRNA were decreased (2 days) and increased (4 days) by PI3K inhibition, while Gstm mRNA increased (P < 0.05) after both time points, and there was no effect on Nrf2 mRNA. PI3K inhibition increased AHR, NRF2 and GSTP protein level. These findings support involvement of ovarian GSTP during DMBA exposure, and indicate a regulatory role for the PI3K signaling pathway on ovarian xenobiotic metabolism gene expression. -- Highlights: ► Ovarian GSTP is activated in response to DMBA exposure. ► AhR and Nrf2 transcription factors are up-regulated by DMBA. ► PI3K signaling regulates Ahr, Nrf2 and Gstp expression. ► GSTP negatively regulates ovarian JNK in response to DMBA exposure.

  14. Miopatia por deficiência de carnitina-palmitil-transferase: relato de 2 casos com dosagens enzimáticas no tecido muscular

    Directory of Open Access Journals (Sweden)

    Lineu Cesar Werneck

    1983-12-01

    Full Text Available Relato dos casos de dois irmãos, que desde a infância apresentavam dores musculares após exercício prolongado ou exposição ao frio, com diminuição da força, à medida que o exercício continuava. Um deles desenvolveu mioglobinúria recorrente e, em um episódio apresentou insuficiência renal aguda, necessitando de diálise peritonial. A investigação laboratorial intercrise foi normal, mas durante o episódio de mioglobinúria, apresentou grande aumento da creatinafosfoquinase. A eletromiografia foi sugestiva de processo de denervação. Teste de produção de lactato durante isquemia foi normal. Biópsias musculares mostraram discreto aumento dos lipídios nas fibras musculares e maior atividade da desidrogenase succínica na histoquímica. O estudo bioquímico do tecido muscular dos dois pacientes, revelou importante redução da atividade da carnitina-palmitil-transferase, com atividade normal da carnitina-octanoil-transferase e carnitina-acetil-transferase. São discutidas as vias metabólicas, sua importância na manutenção da energia muscular durante o exercício prolongado e o papel dos ácidos graxos como fonte energética muscular durante condições normais e patológicas.

  15. Recurrent oral angioleiomyoma

    Directory of Open Access Journals (Sweden)

    V G Mahima

    2011-01-01

    Full Text Available Angioleiomyomas are vascular variant of leiomyomas which are benign tumors of smooth muscle. They are exceedingly rare in the oral cavity. Malignant transformation of these tumors has also been reported occasionally which warrants knowledge of this soft tissue tumor. A 57 year old male patient reported with a 15 day history of an asymptomatic growth that had started insidiously in his lower left back tooth region. Clinical examination revealed a solitary, oval, sessile growth in the mandibular left retro molar region. Excisional biopsy was suggestive of Angioleiomyoma. A recurrence of the same was noted two months later which was also histopathologically reported as Angioleiomyoma. The same was confirmed using special stains. This case reports an unusual presentation of Angioleiomyoma with regards to both recurrence as well as rapid growth. It is important to be well aware of this uncommon entity as these tumors often can mimic or transform into malignancy. Precise clinicopathological examinations are therefore invaluable in establishing an accurate diagnosis and delivering suitable treatment.

  16. Oral contraception following abortion

    Science.gov (United States)

    Che, Yan; Liu, Xiaoting; Zhang, Bin; Cheng, Linan

    2016-01-01

    Abstract Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs postabortion. We conducted this systematic review and meta-analysis in the present study reported immediate administration of OCs or combined OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies. A total of 8 major authorized Chinese and English databases were screened from January 1960 to November 2014. Randomized controlled trials in which patients had undergone medical or surgical abortions were included. Chinese studies that met the inclusion criteria were divided into 3 groups: administration of OC postmedical abortion (group I; n = 1712), administration of OC postsurgical abortion (group II; n = 8788), and administration of OC in combination with traditional Chinese medicine postsurgical abortion (group III; n = 19,707). In total, 119 of 6160 publications were included in this analysis. Significant difference was observed in group I for vaginal bleeding time (P = 0.0001), the amount of vaginal bleeding (P = 0.03), and menstruation recovery period (P abortion (P abortion, and reduce the risk of complications and unintended pregnancies. PMID:27399060

  17. Oral sensations and secretions.

    Science.gov (United States)

    Running, Cordelia A

    2018-04-10

    Sensations experienced in the mouth influence food choices, both immediately and in the long term. Such sensations are themselves influenced by experience with flavors, the chemical environment of the mouth, genetics of receptors for flavors, and individual behavior in the chewing of food. Gustation, the sense of taste, yields information about nutrients, influences palatability, and feeds into the human body's preparation to receive those nutrients. Olfaction, the sense of smell, contributes enormously to defining and identifying food flavors (and is experienced even after placing food inside the mouth). Another vital component of food flavor is texture, which contributes to palatability, especially if a food's texture violates a person's expectations. Next, chemesthesis is the sense of chemically induced irritancy and temperature, for example spiciness and stinging. All of these sensations are potentially modified by saliva, the chemical and physical media of the mouth. As a person experiences the culmination of these oral sensations, modified through an individual's own unique saliva, the flavors in turn influence both what and how a person eats. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Oral cavity eumycetoma

    Directory of Open Access Journals (Sweden)

    Gisele Alborghetti Nai

    2011-06-01

    Full Text Available Mycetoma is a pathological process in which eumycotic (fungal or actinomycotic causative agents from exogenous source produce grains. It is a localized chronic and deforming infectious disease of subcutaneous tissue, skin and bones. We report the first case of eumycetoma of the oral cavity in world literature. CASE REPORT: A 43-year-old male patient, complaining of swelling and fistula in the hard palate. On examination, swelling of the anterior and middle hard palate, with fistula draining a dark liquid was observed. The panoramic radiograph showed extensive radiolucent area involving the region of teeth 21-26 and the computerized tomography showed communication with the nasal cavity, suggesting the diagnosis of periapical cyst. Surgery was performed to remove the lesion. Histopathological examination revealed purulent material with characteristic grain. Gram staining for bacteria was negative and Grocott-Gomori staining for the detection of fungi was positive, concluding the diagnosis of eumycetoma. The patient was treated with ketoconazole for nine months, and was considered cured at the end of treatment. CONCLUSION: Histopathological examination, using histochemical staining, and direct microscopic grains examination can provide the distinction between eumycetoma and actinomycetoma accurately.

  19. Identification of an enhancer element of class Pi glutathione S-transferase gene required for expression by a co-planar polychlorinated biphenyl.

    OpenAIRE

    Matsumoto, M; Imagawa, M; Aoki, Y

    1999-01-01

    3,3',4,4',5-Pentachlorobiphenyl (PenCB), one of the most toxic co-planar polychlorinated biphenyl congeners, specifically induces class Pi glutathione S-transferase (GSTP1) as well as cytochrome P-450 1A1 in primary cultured rat liver parenchymal cells [Aoki, Matsumoto and Suzuki (1993) FEBS Lett. 333, 114-118]. However, the 5'-flanking sequence of the GSTP1 gene does not contain a xenobiotic responsive element, to which arylhydrocarbon receptor binds. Using a chloramphenicol acetyltransferas...

  20. Targeted cytosine deaminase-uracil phosphoribosyl transferase suicide gene therapy induces small cell lung cancer-specific cytotoxicity and tumor growth delay

    DEFF Research Database (Denmark)

    Christensen, Camilla L; Gjetting, Torben; Poulsen, Thomas Tuxen

    2010-01-01

    Small cell lung cancer (SCLC) is a highly malignant cancer for which there is no curable treatment. Novel therapies are therefore in great demand. In the present study we investigated the therapeutic effect of transcriptionally targeted suicide gene therapy for SCLC based on the yeast cytosine...... deaminase (YCD) gene alone or fused with the yeast uracil phosphoribosyl transferase (YUPRT) gene followed by administration of 5-fluorocytosine (5-FC) prodrug. Experimental design: The YCD gene or the YCD-YUPRT gene was placed under regulation of the SCLC-specific promoter insulinoma-associated 1 (INSM1...