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Drosophila GSTs display outstanding catalytic efficiencies with the environmental pollutants 2,4,6-trinitrotoluene and 2,4-dinitrotoluene
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0001-6258-1443
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-6416-064X
2016 (English)In: Biochemistry and Biophysics Reports, ISSN 2405-5808, Vol. 5, 141-145 p.Article in journal (Refereed) Published
Abstract [en]

The nitroaromatic explosive 2,4,6-trinitrotoluene (TNT) and the related 2,4-dinitrotoluene (DNT) aretoxic environmental pollutants. The biotransformation and detoxication of these persistent compoundsin higher organisms are of great significance from a health perspective as well as for the biotechnological challenge of bioremediation of contaminated soil. We demonstrate that different human glutathionetransferases (GSTs) and GSTs from the fruit fly Drosophila melanogaster are catalysts of the biotransformationof TNT and DNT. The human GSTs had significant but modest catalytic activities with both DNT and TNT. However, D. melanogaster GSTE6 and GSTE7 displayed outstanding high activities withboth substrates.

Place, publisher, year, edition, pages
2016. Vol. 5, 141-145 p.
Keyword [en]
Glutathione conjugation, 2, 4, 6-trinitrotoluene detoxication, 2, 4-dinitrotoluene detoxication, Drosophila GSTs, Human GSTs
National Category
Biochemistry and Molecular Biology Chemical Sciences
Research subject
Neurochemistry with Molecular Neurobiology
URN: urn:nbn:se:su:diva-126346DOI: 10.1016/j.bbrep.2015.12.003OAI: diva2:899224
Swedish Research Council, 2012-5161
Available from: 2016-02-01 Created: 2016-02-01 Last updated: 2016-02-23Bibliographically approved
In thesis
1. Studies on Human and Drosophila melanogaster Glutathione Transferases of Biomedical and Biotechnological Interest
Open this publication in new window or tab >>Studies on Human and Drosophila melanogaster Glutathione Transferases of Biomedical and Biotechnological Interest
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Glutathione transferases (GSTs, EC. are multifunctional enzymes that are universally distributed in all cellular life forms. They play important roles in metabolism and detoxication of endogenously produced toxic compounds and xenobiotics. GSTs have gained considerable interest over the years for biomedical and biotechnological applications due to their involvement in the conjugation of glutathione (GSH) to a vast array of chemical species. Additionally, the emergence of non-detoxifying functions of GSTs has further increased their biological significance. The present work encompasses four scientific studies aimed at investigating human as well as fruit fly Drosophila melanogaster GSTs.

Paper I presents the immobilization of GSTs on nanoporous alumina membranes. Kinetic analyses with 1-chloro-2,4-dinitrobenzene followed by specificity screening with alternative substrates showed a good correlation between the data obtained from immobilized enzymes and the enzymes in solution. Furthermore, immobilization showed no adverse effects on the stability of the enzymes. Paper II presents inhibition studies of human hematopoietic prostaglandin D2 synthase (HPGDS), a promising therapeutic target for anti-allergic and anti-inflammatory drugs. Our screening results with an FDA-approved drug library revealed a number of effective inhibitors of HPGDS with IC50 values in the low micromolar range. Paper III concerns the toxicity of organic isothiocyanates (ITCs) that showed high catalytic activities with GSTE7 in vitro. The in vivo results showed that phenethyl isothiocyanate (PEITC) and allyl isothiocyanate in millimolar dietary concentrations conferred toxicity to the adult fruit flies leading to death or shortened life-span. The transgenic female flies overexpressing GSTE7 showed increased tolerance against PEITC toxicity compared to the wild-type. However, the effect was opposite in male flies overexpressing GSTE7 after one week exposure. Notably, the transgene enhanced the oviposition activity of flies with and without ITCs exposure. Paper IV highlights Drosophila GSTs as efficient catalysts of the environmental pollutant and explosive 2,4,6-trinitrotoluene and the related 2,4-dinitrotoluene degradation. This result suggests the potential of GST transgenes in plants for biotransformation and phytoremediation of these persistent environmental pollutants. 

Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University, 2016. 43 p.
glutathione transferases, detoxication, hpgds inhibition, immobilization, isothiocyanates, drosophila GSTs, environmental pollutants
National Category
Chemical Sciences Biochemistry and Molecular Biology
Research subject
Neurochemistry with Molecular Neurobiology
urn:nbn:se:su:diva-126723 (URN)978-91-7649-349-6 (ISBN)
Public defence
2016-03-18, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Available from: 2016-02-24 Created: 2016-02-12 Last updated: 2016-02-24Bibliographically approved

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Mazari, Aslam M. A.Mannervik, Bengt
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