Glutathione transferases are multifunctional enzymes. Some of the known functions of the enzymes are biotransformation of xenobiotics, countering oxidative stress and participating in cell regulatory functions. As the isoforms present in number of classes the purification of a particular isoform for characterization is a challenging task. In insect, the study of GSTs is focusing on their roles in development of insecticide resistance. There were evident that certain classes of the enzymes are reactive towards conjugating the pesticides. This makes GSTs one of the enzymes of intention in the discipline of pesticide control management.
- Glutathione transferases
- insecticide resistance
This chapter will review literatures concerning glutathione S-transferases from a broad point of view but with an emphasis on their properties, functions, and purification strategies and its challenges. The focus will be on the occurrence of GSTs in insects and the understanding of their role in insecticide resistance. The intention of this review will also be to look into the relationship of particular isoforms of the GSTs to responses to most used insecticides in agriculture.
2. Glutathione-dependent enzymes
Glutathione (GSH, γ-glutamylcysteinylglycine) is a low molecular weight sulfhydryl compound. It is a tripeptide with the sequence glutamic acid, cysteine, and glycine. GSH is a crystalline solid with a melting point of 192–195°C and molecular weight of 307.33. It dissolves readily in water. There are two peptide bonds, two carboxylic acid groups (p
A variety of different enzymes utilize glutathione in a variety of biotransformations . Glutathione reductase (GR) catalyses the reduction of GSSG (oxidized glutathione) using NADPH as a reductant. GR is important in maintaining the high cellular reduction potential.
Selenium-dependent glutathione peroxidase (GPOX) is another type of GSH-requiring enzyme that catalyses the reduction of peroxides using GSH as the reducing agent. There are the glutathione S-transferases (GSTs) that are also GSH dependent enzymes with many catalytic activities including the conjugation of GSH to xenobiotics [2,3].
3. Glutathione S-transferases (GSTs, E.C. 2.5. 1.18) with diverse functions
GSTs are found in almost every species, including plants  microorganisms [5,6], and animals . GSTs are divided into classes based on their amino acid sequence, immunological, kinetic, and structural properties. In mammals, at least nine classes of GSTs have been identified, namely, Alpha, Mu, Pi, Theta, Omega, Sigma, Zeta, Kappa, and a microsomal class. Human GSTs have been reviewed in reference [8, 9], and . The majority of GSTs are found mainly in the cytosol. Each class consists of one or more protein isoforms. The classes are defined such that the amino acid identity between two isoforms of the same class is more than 50% but more than 30% if they are in different classes . Human cytosolic GSTs are not only in cytoplasm but may also be localized in the mitochondria or the nucleus . The microsomal family of membrane-bound GSTs is also reported and is different from cytosolic GSTs in molecular weight, subunit structure, and immunological reactivity [13-15]. The microsomal GSTs are trimeric, membrane-bound proteins. Mitochondrial GST 13-13 previously purified from rat liver  has been later characterized as GSTK1-1 of a Kappa class GST . The Kappa class GSTs are located in mammalian mitochondria and peroxisomes [18,19] and are structurally distinct from the microsomal and cytosolic GSTs .
GSTs have a broad and overlapping specificity. Among the reactions catalyzed by GSTs are the substitution of halogens in halogenohydrocarbon, the addition to double bonds, the cleavage of epoxides, and the reduction of organic peroxides. 1-Chloro-2,4-dinitrobenzene (CDNB) is the most common substrate used to assay GSTs in the laboratory as most, but not all, GSTs show catalytic activity with it. Other substrates that have been commonly used to characterize the enzymes are 1,2-dichloro-4-nitrobenzene (DCNB), trans-4-phenyl-3-butene-2-one (PBO), ethacrynic acid (EA), 1,2-epoxy-3-nitrophenoxypropane (EPNP),
GSTs catalyze the nucleophilic attack by the thiol group of reduced glutathione (GSH) on a wide range of electrophilic substrates. GSTs play important roles in the development of resistance to a variety of exogenous xenobiotics, such as chemotherapeutic drugs , chemical carcinogens , herbicides , and insecticides .
3.1. Conjugation of exogenous toxins (Biotransformation)
GSTs play important roles in the protection of macromolecules from attack by reactive electrophiles. The enzymes generally exist in dimeric forms with a subunit molecular weight of approximately 26 kDa. GSTs occur both as homo- and heterodimers. The cytosolic isoenzymes have two active sites per dimer that behave independently of one another . Each active site consists of at least two ligand-binding regions, namely, the GSH binding site (hydrophilic G-site), which is specific for GSH, and the electrophile-binding site (hydrophobic H-site), which is less specific and thus enables GSTs to react with a wide variety of xenobiotics . A review in reference  listed xenobiotics that could be conjugated by GSTs. These include halogenonitrobenzenes, organophosphorus compounds, steroids, αβ-unsaturated carbonyl compounds, aryl halides epoxides, quinones, isothiocyanates, and arylnitro compounds.
The conjugations catalyzed by the GSTs occur between the nucleophilic GSH and the compounds possessing a sufficiently electrophilic center . The GSTs function by decreasing the p
This GSH conjugation has been shown to occur in mammals, birds, reptiles, amphibians, fish, insects, and other invertebrates , and it is the first step of mercapturic acid formation that is one of the metabolic pathways for detoxication of xenobiotics
Prostaglandin D-synthase, the enzyme involved in production of the D and J series of prostanoids, was characterized as belonging to the Sigma class of GSTs . GSTs also participate in the isomerization of biologically active molecules. A prostaglandin-H E-isomerase of
Human GST A3-3 was shown to efficiently catalyze the double-bond isomerization of Δ5-androstene-3,17-dione and Δ5-pregnene-3,20-dione . Human GSTs were reported to act as retinoic isomerases that catalyze the steric conversion of 13-
3.2. Participation in countering oxidative stress
Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide, and the hydroxyl radical are constantly produced during normal aerobic metabolism. The free radicals may attack the polyunsaturated fatty acyl moieties and lead to the peroxidation of lipid bio-membranes. The cleavage of polyunsaturated fatty acids is known to be associated with formation of organic hydroperoxides and reactive aldehydes. These include alkanals, alkenals, and malondialdehyde. These may interfere with several biological processes such as DNA and protein synthesis by inhibition of specific enzyme reactions [34,35].
Peroxidized lipids, produced during oxidative stress, are substrates for GSTs. 4-Hydroxyalkenals are derived from membrane-bound phospholipid hydroperoxides. They were shown to be efficiently conjugated to GSH by GST A4-4 [36,37]. A membrane-bound mouse GSTA4-4 and a rat GSTA8-8 [39,40] were also shown efficiently conjugating 4-hydroxyalkenals. It was reported that transfected mGSTA4 protects HL 60  and K562 human erythroleukemia cells  against 4-hydroxynonenal-induced apoptosis.
Free radicals can also cause DNA peroxidation. The toxicity of thymine propenal, which is generated by oxidative damage to DNA, was shown to be substantially reduced when HeLa cells received GSTP1-1 and GSH . The rat GST6-6 had previously shown active toward thymine hydroperoxide .
Within the cells, peroxides occur either as hydrogen peroxide (H2O2) or organic hydroperoxides, such as fatty acid and phospholipid hydroperoxides. GSTs protect tissues from endogenous organic hydroperoxides produced during oxidative stress [35,45]. Some GSTs have shown selenium-independent H2O2 and organic hydroperoxidase activity, which are involved in free radical reactions during oxidative stress . A microsomal GST A1-1 of sheep liver exhibited peroxidase activity toward fatty acid hydroperoxides such as linoleic and arachidonic acid hydroperoxides . Human GSTs, such as hGSTA1-1 and hGSTA2-2 [48,49], also exhibited glutathione peroxidase activity toward phospholipid hydroperoxide . Other workers observed elevated GSTs in
3.3. Involve in cells regulatory functions
Recent studies of GSTs have demonstrated that a Pi class GST is involved in regulation of c-Jun N-terminal kinase (JNK) signaling in mammals. GSTP interacts with c-Jun N-terminal kinase 1 (JNK1) suppressing the basal kinase activity [52,53]. A model of GST inhibition of JNK signaling was proposed . Under a nonstressed condition, GSTp can exist as free dimeric enzyme or complexed with Jun–JNK thus inhibiting JNK. Upon stress, GSTP forms larger aggregates, which are unable to associate with the Jun–JNK complex, thus enabling the JNK phosphorylation of c-Jun. Phosphorylated Jun can act as a stable and active transcription factor. The accumulation of ROS in response to oxidative stress results in the activation of multiple stress kinase cascades and an elevated level of GSTp expression .
Apoptosis signal-regulating kinase 1 (ASK 1) can activate the JNK and the p38 signaling pathways. It plays important role in stress-induced apoptosis. Mouse GSTM1-1 was shown to physically interact with ASK1 and repress ASK1-mediated signaling [55,56].
It has also been reported that human GST class Omega, GSTO1-1, modulates calcium channel (ryanodine receptors, RyRs) protecting mammalian cells from apoptosis induced by calcium (Ca2+) mobilization . It was suggested that RyRs has two binding sites for GSTO1-1. The mammalian protein Bax (21 kDa) is an inducer of apoptosis. A study  has reported a plant GST (Theta class) as one of the Bax-inhibiting plant proteins, which prevent apoptosis in plants. GSTP1-1 was proposed  interacting with physiological nitric oxide (NO) carriers such as S-nitrosoglutathione (GSNO) and dinitrosyl-diglutathionyl iron complex (DNDGIC). In the absence of GSH, GSNO interacts with and modifies Cys47 and Cys101 residues of GSTP1-1 by an
4. GSTs in insects
In insects, GSTs are classified into two groups, class I and class II GSTs . According to a recent proposed classification , an insect-specific Delta class GST is classified as a class I GST. This includes those from
Studies on insect GSTs were reviewed in detail [7,23,69]. GSTs have been detected in Lepidoptera, Diptera, Coleoptera, Dictyoptera, and Hymenoptera . At present, only few insect GST structures are known. These include that from the Australian sheep blowfly,
4.1. Characterization of GSTs and its challenges
A problem faced during the extraction of insect GSTs is the possible presence of endogenous inhibitors . Quinones and catecholamines released during homogenization can inhibit the GSTs’ activity . The last-named authors suggested the inclusion of GSH in the homogenizing buffer to protect the GSTs from inhibition. Polyphenol pigments have also been shown to inactivate the GSTs. The inclusion of 5–10 mM cysteine in the homogenate prevents the formation of polyphenol. The endogenous inhibitors can also be removed by initial loading of the crude homogenate through an ion exchange or gel filtration column . There are many different strategies employed to purify the GSTs from insects. One of those is by using affinity chromatography with several different affinity matrices. A ligand, sulfobromophthalein-glutathione conjugate (BSP), has been immobilized to an agarose matrix by using either cyanogen bromide  or epichlorohydrin activation . The enzymes bind selectively to the resulting matrices when a crude homogenate is applied directly to the columns. The bound enzymes can be eluted by using 0–5 mM of BSP  or 1–5 mM GSH solution . The matrix has been used to purify a GST to homogeneity from
Investigation of multiple forms of GSTs with different isoelectric points could be performed by using isoelectrofocusing [78,88,89] or chromatofocusing . Purification by affinity chromatography followed by isoelectrofocusing revealed the existence of multiple forms of GSTs , in house fly strains Rutgers, Cornell R, and Hirokawa. The presence of multiple isoenzymes of GSTs have also been reported in other species, such as
4.2. GSTs and insecticide resistance
The majority of studies on insect GSTs have focused on their role in conferring insecticide resistance. A review  has indicated the importance of genetic and biochemical mechanisms in
High levels of GSTs have consistently been observed in resistant insect strains and play a major role in insecticide resistance [77,98,99]. Increased activity of GSTs in housefly was found to be associated with resistance to azinphosmethyl , parathion , phyrethroids , tetrachlorovinphos  and malathion .
GSTs have been shown to play an important role in insecticide resistance. The catalysis of conjugation of insecticides, such as organophosphorus compounds, chlorinated hydrocarbons, and carbamate insecticides is shown in Figure 3. It was classified three types of reactions catalyzed by GSTs in metabolism of organophosphorus insecticides . The detoxification of organophosphates (OP) occurs by the conjugation of GSH to OP via an O-dealkylation or O-dearylation conjugation, which later forms O-alkyl, O-aryl, and phosphonate conjugates which are all less toxic derivatives.
For the organochlorine insecticides the process involves dehydrochlorination and the GSH conjugation to the parent molecules . Phyrethroids, however, trigger oxidative damage in cell. Therefore, GSTs role has been detoxifying the lipid peroxidation products resulted by the insecticide . It is well known that some classes of GSTs have shown peroxidases activities. For example, a Delta class GST of
GSTs are enzymes of multi-functional roles. Studies in insect have always directed the role of GSTs in conferring resistance toward insecticides resistance. Several classes of GSTs have been shown to counter the insecticides through direct GSH conjugation process and also their ability to react against lipid peroxidation products. This is due to the fact that some insecticides cause oxidative damage. Direct isolation of responsible GST from insect has been of a challenge due to limited ability of available affinity matrix to capture all classes of GSTs. The characterization of recombinant GSTs could have led to a better understanding of the mechanism of action and thus the regulation of the GSTs upon exposure to insecticides. The availability of fully sequence genomes in model insect such as
The author is grateful to Dr A.G. Clark (Victoria University of Wellington) and the Ministry of Higher Education (FRGS: FP052-2014A) for financial assistance.
Fukami J-I. Metabolism of several insecticides by glutathione S-transferase. Pharmacol. Ther. 1979;10: 473–514.
Mannervik B. Glutathione and evolution of enzymes for detoxication of products of oxygen metabolism. Chemica Scripta. 1986;26: 281–284
van Bladere PJ. Glutathione conjugation as a bioactivation reaction. Chem. Biol. Interact. 2000;129: 61–76
Edwards R, Dixon P, Walbot V. Plant glutathione S-transferases: Enzymes with multiple functions in sickness and health. Trends Plant Sci. 2000;5: 193–198
Sheehan D, Casey JP. Microbial glutathione S-transferases. Comp. Biochem. Physiol. 1993;104: 1–6
Vuilleumier S. Bacterial glutathione S-transferases: What are they good for? J. Bacteriol. 1997;179: 1431–1441
Clark AG. The comparative enzymology of the glutathione S-transferases from non-vertebrate organisms. Comp. Biochem. Physiol. 1989;92: 419–446
Ketterer B. A bird’s view of the glutathione transferase field. Chem. Biol. Interact. 2001;138: 27–42
Sheeha, D, Meade G, Foley VM, Dowd CA. Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J. 2001;360: 1–16
Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu. Rev. Pharmacol. Toxicol. 2005;45: 51–88
Mannervik B, Awasthi YC, Board PG, Hayes JD, Di Ilio C, Ketterer B, Litowsky I, Morgenstern R, Muramatsu M, Pearson WR., Picket CB, Sat K, Widersten M, Wolf C.R. Nomenclature for human glutathione transferases. Biochem. J. 1992;282: 305–306
Johansson AS, and Mannervik, B. Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerisation in the biosynthetic pathway of steroid hormones. J. Biol. Chem. 2001;276: 33061–33065
Morgenstern R, Meijer J, DePierre JW, Ernster, L. Characterization of rat-liver microsomal glutathione S-transferase activity. Eur. J. Biochem. 1980;104: 167–174
Morgenstern R, Guthenberg C, Depierre JW. Microsomal glutathione S-transferase. Purification, initial characterisation and demonstration that it is not identical to cytosolic glutathione S-transferase A, B, C. Eur. J. Biochem. 1982;128: 243–248
Morgenstern R, DePierre JW. Microsomal glutathione transferase : Purification in unactivated form and further characterization of the activation process, substrate specificity and amino acid composition. Eur. J. Biochem. 1983;134: 5911–597
Harri, JM, Meye DJ, Coles B, Ketterer, B. A novel glutathione transferase (13-13) isolated from the matrix of rat liver mitochondria having structural similarity to class theta enzymes. Biochem. J. 1991;278: 137–141
Pemble SE, Wardle AT, Taylor JB. Glutathione S-transferase class Kappa : characterisation by the cloning of rat mitochondrial GST and identification of a human homologue. Biochem J. 1996;319: 749–754
Morel F, Rauch C, Petit E, Piton, Theret N, Coles B, Guillouzo A. Gene and protein characteization of the human glutathione S-transferase Kappa and evidence for peroxisomal localization. J. Biol. Chem. 2004;279: 16246–16253.
Landler JE, Parsons JF, Rife C, Gillilard GL, Armstrong RN. Parallel evolutionary pathways for glutathione transferases: structure and mechanisms of the mitochondrial class Kappa rGSTK1-1. Biochemistry. 2004;43: 352–361
Robinson A, Huttley GA, Booth HS, Board, PG. Modelling and bioinformatics studies of the human Kappa-class glutathione transferase predict a novel third glutathione transferase family with similarity to prokaryotic 2-hydroxychromene-2-carboxylate isomerase. Biochem J. 2004;379: 541–552.
Haye, JD, Pulford DJ. The glutathione S-transferase supergene family: Regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit. Rev. Biochem. Mol. Biol. 1995;30: 445–600
Coles B, Ketterer B. The role of glutathione and glutathione S-transferases in chemical carcinogenesis. Biochem. Mol. Biol. 1990;25: 47–70
Danielson UH, Mannervik B. Kinetic independence of the subunits of cytosolic glutathione S-transferase from the rat. Biochem. J. 1985;231: 263–267
Dir H, Reinemer P, Huber R. X-ray crystal structure of cytosolic glutathione S-transferases: implication for protein architecture, substrate recognition and catalytic function. Eur. J. Biochem. 1994;220: 645–661
Chasseaud LF. The role of glutathione and glutathione S-transferases in the metabolism of chemical carcinogens and other electrophilic agents. Adv. Cancer Res. 1979;29: 175–274
Boyland E, Chasseaud LF. The role of glutathione and glutathione S-transferases in mercapturic acid biosynthesis. Adv. Enzymol. 1969;32: 173-219
Picket CB, Lu AYH, Glutathione S-transferases: gene structure, regulation and biological function. Annu. Rev. Biochem. 1989;58: 743–764
Kanaoka Y, Fujimori K, Kikuno R, Sakaguchi, Y, Urade, Y, and Hyaishi, O. Structure and chromosomal localization of human and mouse genes for hematopoeitic prostaglandin D synthase. Eur. J. Biochem. 2000.;267: 3315–3322
Meyer DJ, Muimo R, Thomas M, Coates D. and Isaac, R.E. Purification and characterization of prostaglandin-H E-isomerase, a sigma-class glutathione S-transferase, from Ascaridia galli. Biochem. J. 1996;313: 223–227
Meyer DJ, Thomas M. Characterization of rat spleen prostaglandin H D-isomerase as a sigma-class GSH transferse. Biochem. J. 1995;311: 739–742
Board PG, Taylor MC, Coggan M, Parke MW, Lantum HB, Anders MW. Clarification of the role of key active site residues of glutathione transferase zeta/maleylacetoacetate isomerase by a new spectrometric technique. Biochem. J. 2003;374: 731–737
Jakoby WB, Habig WH, 1980. Glutathione S-transferases. In Enzymatic Basis of Detoxificaton Vol II. Academic Press Inc.
Chen H, Juchau MR. Recombinant human glutathione S-transferases catalyse enzymic isomerization of 13- cis-retinoic acid to all- trans-retinoic acid in vitro. Biochem. J. 1998;336: 223–226
Esterbauer H, Cheeseman KH, Dianzani MU, Poli G, and Slater TF. Separation and characterisation of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes. Biochem. J. 1982;208: 129–140
Ketterer B, Meyer DJ, Taylor JB, Pemble S, Coles B, Fraser G. GSTs and protection against oxidative stress. In : Proceedings of 3rd International GST conference, Scotland : Taylor and Francis, London; 1989. p. 97–109.
Cheng JZ, Yang Y, Singh SP, Singhal SS, Awasthi S, Pan SS, Singh SV, Awasthi YC. Two distinct 4-hydroxynonenal metabolising glutathione S-transferase isozymes are differentially expressed in human tissues. Biochem. Biophys. Res. Commun. 2001;282: 1268–1274
Hubatsch I, Ridderström M, Mannervik B. Human glutathione transferase A4-4: an alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation. Biochem. J. 1998;330: 175–179
Singh SP, Janecki AJ, Srivastava SK, Awasthi S, Awasthi YC, Xia SJ, Zimniak P. Membrane association of glutathione S-transferase mGSTA4-4, and enzyme that metabolizes lipid peroxidation products. J. Biol. Chem. 2002;277: 4232–4239
Jensson H, Guthenber, C, Ålin P, Mannervik B. Rat glutathione transferase 8-8, an enzyme efficiently detoxifying 4-hydroxyalk-2-enals. FEBS Lett. 1986;203: 207–209
Stenberg G, Ridderström M, Engström Å, Pemble SE, Mannervik B. Cloning and heterologous expression of cDNA encoding class alpha rat glutathione transferase 8-8, an enzyme with high catalytic activity towards genotoxic α,β-unsaturated carbonyl compounds. Biochem. J. 1992;284: 313–319
Cheng JZ, Singhal SS, Sharma A, Saini M, Yang Y, Awasthi S, Zimniak P, Awasthi YC. Transfection of mGSTA4 in HL-60 cells protects against 4-hydroxynonenal-induced apoptosis by inhibiting JNK-mediated signalling. Arch. Biochem. Biophy. 2001;392:197–207
Cheng JZ, Singhal SS, Saini M, Singhal J, Piper JT, van Kuijk FJ, , Zimniak GM, Awasthi, YC, Awasthi S. Effects of mGST A4 transfection on 4-hydroxynonenal-mediated apoptosis and differentiation of K562 human erythroleukimia cells. Arch. Biochem. Biophy. 1999;372: 29–36
Berhane K, Widersten M, Engstrom A, Kozarich JW, Mannervik B. Detoxication of base propenals and other αβ-unsaturated aldehyde products of radical reaction and lipid peroxidation by human GSTs. Proc. Natl. Acad. Sci. U. S. A. 1994;91: 1480–1484
Tan KH, Meyer DJ, Ketterer B. Thymine hydroperoxide, a substrate for rat Se-dependent glutathione peroxidase and glutathione transferase isoenzymes. FEBS Lett. 1986;207: 231–233
Storey KB.. Oxidative Stress : Animal adaptations in nature. Braz. J. Med. Biol. Res. 1996;29: 1715-1733
Wilce MCJ, Parker MW. Structure and function of glutathione S-transferses. Biochem. Biophys. Acta. 1994;205:1–18
Prabhu KS, Reddy PV, Gumpricht E, Hildenbrandt GR, Scholz RW, Sordillo LM, Reddy CC. Microsomal glutathione S-transferase A1-1 with glutathione peroxidase activity from sheep liver: molecular cloning, expression and characterisation. Biochem. J. 2001;360: 345–354
Yang Y, Cheng JZ, Singhal SS, Sain, M, Pandya U, Awasthi S, Awasthi YC. Role of glutathione S-transferases in protection against lipid peroxidation. J. Biol. Chem. 2001;276: 19220–19230
Zhou ZH, Syvanen M. A complex glutathione transferase gene family in the housefly Musca domestica. Mol. Gen. Genet. 1997;256: 187–194
Hurst R, Bao Y, Jemth P, Mannervik B, Williamson G. Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferase. Biochem. J. 1998;332: 97–100
Vontas JG, Small GJ, Hemingway J. Glutathione S-transferases as antioxidant defence agents confer pyrethroid resistance in Nilaparvata lugens. Biocem. J. 2001;357: 65–72
Adler V, Yin Z, Fuchs SY, Benezra M, Rosario L, Tew KD, Pincus MR, Sardana M, Henderson CJ, Wolf CR, Davis RJ, Ronai Z. Regulation of JNK signalling by GSTp. EMBO J. 1999;18: 1321–1334
Wang T, Arifoglu P, Ronai Z, Tew KD. Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal Kinase (JNK1) signaling through interaction with C-terminus. J. Biol. Chem. 2001;276: 20999–21003
Ainbinder E, Bergelson S, Pinkus R, Daniel V. Regulatory mechanisms involved in activator-protein-1 (AP-1)-mediated activation of glutathione S-transferase gene expression by chemical agents. Eur. J. Biochem. 1997;243: 49–57
Cho SG, Lee YH, Park HS, Ryoo K, Kang KW, Park J, Eom SJ, Kim MJ, Chang TS, Choi, SY, Shim J, Kim Y, Dong MS, Lee MJ, Kim SG, Ichijo H, Choi EJ. Glutathione S-transferase Mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J. Biol. Chem. 2001;276: 12749–12755
Gilot D, Loyer P, Corlu A, Glaise D, Lagadic-Gossmann D, Atfi A, Morel F, Ichijo H, Guguen-Guillouzo C. Liver protection from apoptosis requires both blockage of initiator caspase activities and inhibition of ASK1/JNK pathway via glutathione S-transferase regulation. J. Biol. Chem. 2002;277: 49220–49229
Dulhunty A, Gage P, Curtis S, Chelvanayagam G, Board P. The glutathione transferase structural family includes a nuclear chloride channel and a rynodine receptor calcium release channel modulator. J. Biol. Chem. 2001;276: 3319–3323
Kampranis SC, Damianova R, Atallah M, Toby G, Kondi G, Tsichlis PN, Makris AM. A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast. J. Biol. Chem. 2000;275: 29207–29297
Lo Bello M, Nuccetelli M, Caccuri AM, Stella L, Parker MW, Rossjohn J, McKinstry WJ, Mozzi AF, Federici G, Polizio F, Pederson JZ, Ricci G. Human glutathione transferase P1-1 and nitric oxide carriers. J. Biol. Chem. 2001;276: 42138–42145
Piredda L, Farrace MG, Belloo ML, Malorni W, Melino G, Petruzzeli R, Piacetini M. Identification of ‘tissue’ transglutaminase binding proteins in neural cells commited to apoptosis. FASEB J. 1999;13: 335–364
Fournier D, Bride JM, Poirie M, Berge JB, Flapp Jr. FW. Insect glutathione S-transferases: biochemical characteristics of the major forms from houseflies susceptible and resistant to insecticides. J. Biol. Chem. 1991;267: 1840–1845
Chelvanayagam G, Parker MW, Board PG. Fly fishing for GSTs: a unified nomenclature for mammalian and insect glutathione transferases. Chem. Biol. Interact. 2001;133: 256–260
Toung YPS, Hsieh TS, Tu CPD. The glutathione S-transferase D genes: a divergently organised, intronless gene family in Drosophila melanogaster. J. Biol. Chem. 1993;268: 9737–9746
Ranson HR, Cornel AJ, Fournier D, Vaughan A, Collins FH, Hemingway J. Cloning and localization of a glutathione S-transferase class I gene Anopheles gambiae. J. Biol. Chem. 1997;272: 5464–5468
Ranson H, Collins J, Hemingway J. The role of alternative mRNA splicing in generating heterogeneity within the Anapholes gambiaeclass I glutathione S-transferase family. Proc. Natl. Acad. Sci. U. S. A. 1998;95: 14284–14289
Beall C, Fryberg C, Song S, Fryberg E. Isolation of Drosophilagene encoding glutathione S-transferase. Biochem. Genet. 1992;30: 515–527
Reiss RA, James AA. A glutathione S-transferase gene of the vector mosquito, Anopheles gambiae. Insect Mol. Biol. 1993;2: 25–32
Ranson H, Rossiter L, Ortelli F, Jensen B, Wang X, Rothe CW, Collins FH, Hemingway J. Identification of a novel class of insect glutathione S-tranferases involved in resistance to DDT in the malaria vector Anopheles gambiaeBiochem J. 2001;359: 295–304
Enayati AA, Ranson H, Hemingway J. Insect glutathione transferases and insecticides resistance. Insect Mol. Biol. 2005;14: 3–8
Oakley AJ, Harnnoi T, Udomsinprasert R, Jirajaroenrat K, Ketterman AJ, Wilce MC. The crystal structures of glutathion S-transferases isoenzymes 1–3 and 1–4 from Anopheles dirusspecies B. Protein Sci. 2001;10: 2176–2185
Udomsinprasert R, Pongjaroenkit S, Wongsantichon J, Oakley AJ, Prapantadhara LA, Wilce MCJ, Ketterman AJ. Identification, characterization and structure of a new Delta class glutathione transferase isoenzyme. Biochem. J. 2005; 388: 763–771
Agianian B, Clayton JD, Leanord K, Tucker P, Bullard B, Gros P. Crystallization and preliminary X-ray analysis of Drosophilaglutathione S-transferase-2. Acta Crystallogr. D. Biol. Crystallogr. 2000;57: 725–727
] Agianian B, Tucker PA, Schouten A, Leonard K, Bullard B, Gros P. Structure of a Drosophilasigma class glutathione S-transferase reveals a novel active site topography suited for lipid peroxidation products. J. Mol. Biol. 2003;326: 151–165
Motoyama N, Kulkarni AP, Hodgson E, Dauterman WC. Endogenous inhibitors of glutathione S-transferase in houseflies. Pestic. Biochem. Physiol. 1978;9: 255–262
Kulkarni AP, Motoyama N, Dauterman WC, Hodgson E. Inhibition of housefly glutathione S-transferase by catecholamines and quinones. Bull. Environ. Contam. Toxicol. 1978;20: 221–232
Clark AG, Letoa M, Ting WS. The purification by affinity chromatography of a glutathione S-transferase from larvae of Galleria mellonella.Life Sci. 1977;20: 141–148
Clark, A.G. and Dauterman, W.C. The characterisation by affinity chromatography of glutathine S-transferases from different strains of housefly. Pestic. Biochem. Physiol. 1982;117: 307-314
Baker WL, Clark AG, Faulds G, Nielson JS. Multiple glutathione S-transferases in Galleria mellonella; their detection with fluorigenic substrates. Insect Biochem. Molec. Biol. 1994;24: 301–307
Clark AG, Dick GL, Martindal SM, Smith JN. Glutathione S-transferases from New Zealand grass crub, Costelytera zealandica.Insect Biochem. 1985;15: 35–44
Clark AG, Shamaan NA. Evidence that DDT-dehydrochlorinase from the housefly is a glutathione S-transferase. Pestic. Biochem. Physiol. 1984;22: 249–261
Clark AG, Marshall, SN, Qureshi AR. Synthesis and use of an isoform-specific affinity matrix in the purification of glutathione S-transferases from the house fly, Musca domestica(L.). Protein Expr. Purif. 1990;1: 121–126.
Alias Z, Clark AG. Studies on the glutathione S-transferase proteome of adult Drosophila melanogaster: responsiveness to chemical challenge. Proteomics. 2007;7: 3618–3628.
Clark AG, Drake B. Purification and properties of glutathione S-transferases from larvae of Wiseana cervinata.Biochem. J. 1984;217: 41–50
Simon PC, van der Jagt DL. Purification of glutathione S-transferases from human liver by glutathione-affinity chromatography. Anal. Biochem. 1977;82: 334–341
Cochrane BJ, Morrissey JJ, LeBlanc GA. The genetics of xenobiotic metabolism in Drosophila. IV. Purification and characterisation of the major glutathione S-transferase. Insect Biochem. 1987;17: 731–738
Toung YP, Hsieh TS, Tu CPD. Drosophilaglutathione S-transferase 1-1 shares a region of sequence homology with the maize glutathione S-transferases III. Proc. Natl. Acad. Sci. U. S. A. 1990;87: 31–35
Mannervik B, Guthenberg C. Glutathione transferase (human placenta). Methods Enzymol. 1981;77: 231–235
Clark AG, Smith JN, Speir TW. Cross specificity in some vertebrate and insect glutathione S-transferases with methylparathion (dimethyl p-nitrophenyl phophorothionate), 1-chloro-2,4-dinitrobenzene and N-crotonyl- N-acetyl cysteamine as substrates. Biochem. J. 1973;135: 285–392
Yawetz A, Koren B. Purification and properties of the Mediterranean fruit fly Ceratitis capitata W.glutathione S-transferase. Insect Biochem. 1984;14: 663–670
Keeran WS, Lee RF. The purification and characterisation of glutathione S-transferase from the hepatopancreas of the Blue Crab, Callinectes sapidus. Arch.Biochem. Biophys. 1975;25: 8670–8673
Clark, A.G. and Dauterman, W.C. The characterisation by affinity chromatography of glutathine S-transferases from different strains of housefly. Pestic. Biochem. Physiol. 1982;117: 307–314.
Grant DF, Dietze EC, Hammock BD. Glutathione S-transferases isoenzymes in: purification, characterisation and isoenzyme-specific regulation. Insect Biochem. 1991;21: 421–433
Chiang FM, Sun CN. Glutathione transferase isoenzymes of diamondback moth larvae and their role in the degradation of some organophosphorus insecticides. Pestic. Biochem. Physiol. 1993;45: 7–14
Kostaropoulos I, Mantzari AE, Papadoupolos AI. Alterations of some glutathione S-transferase characteristics during the development of Tenebrio molitor(Insecta: Coleoptera). Insect Biochem. Mol. Biol. 1996;26: 963–969
Wilson TG. Resistance of Drosophilato toxins. Annu. Rev. Entomol. 2001;46: 545–571.
Morton RA. Evolution of Drosophilainsecticide resistance. Genome. 1992;36: 1–7
Oppenoorth FJ. Biochemistry of insecticide resistance. Pestic. Biochem. Physiol. 14;22: 187–193
Oppenoorth FJ, Rupes V, El-Bashir S, Houx NWH, Voerman S. Glutathione dependent degradation of parathion and its significance for resistance in housefly. Pestic. Biochem. Physiol. 1972;2: 262–269
Motoyama N, Dauterman WC. Interstrain comparison of glutathione-dependent reactions in susceptible and resistant houseflies. Pestic. Biochem. Physiol. 1975;5: 489–495
Motoyama N., Dauterman WC. In vitrometabolism of azinphosmethyl in susceptible and resistant house flies. Pestic. Biochem. Physiol. 1972;2: 113–122
Papadoplus AI., Boukouvala E, Kakaliouras G, Kostaropoulos J, Papadopoulou-Mourkidou. Effect of organophosphate and pyrethroid insecticides on the expression of GST from Tenebrio molitorpupae. Pestic. Biochem. Physiol. 2000;68: 26–33
Oppenoorth FJ, van der Pas LJT, Houx NWH. Glutathione S-transferase and hydrolytic activity in a tetrachlorvinphos-resistant strain of housefly and their influence on resistance. Pestic. Biochem. Physiol. 1979;11: 176-188
Niwa Y, Miyata T, Saito T. In vitro metabolism of malathion by malathion resistant and susceptible strains of houseflies, Musca domestica. J. Pestic. Sci. 1977;2: 151-157
Houpt DR, Pursey JC, Morton RA. Genes controlling malathion resistance in laboratory-selected population of Drosophila melanogaster. Genome. 1988;30: 844–853
Cochrane JB, LeBlanc GA. Genetic of metabolism in Drosophila. I. Genetic and environmental factors affecting glutathione S-transferase in larvae. Biochem. Pharmacol. 1986;35: 1679–1684
Shepanski MC, Glover TJ, Kuhr RJ. Resistance of Drosophilato DDT. J. Econ. Entomol. 1977;70: 539–543
Wilson JA, Clark AG. The role of E3 esterase, glutathione S-transferases and other nonoxidative mechanisms in resistance to diazinon and other organophosphate insecticides in Lucilia cuprina. Pestic. Biochem. Physiol. 1996;54: 85–95
Motoyama N, Dauterman WC. Glutathione S-transferases: Their role in the metabolism of organophosphorus insecticides. Rev. Biochem. Toxicol. 1980;2: 49–69
Lumjuan N, McCarroll L, Prapanthadara L, Hemingway J, Ranson H. Elevated activity of an Epsilon class glutathione transferase confers DDT resistance in the dengue vector, Aedes aegypti.Insect Biochem. Mol. Biol. 2005;35: 861–871
Ding Y, Hawkes N, Meredith J, Eggleston P, Hemingway, J, Ranson, H. Characterization of the promoters of Epsilon glutathione transferases in the mosquito Anopheles gambiaeand their response to oxidative stress. Biochem J. 2005;387: 879–888.
Sawicki R , Singh S P, Mondal, A K, Benes H, Zimniak P. Cloning, expression and biochemical characterization of one Epsilon-class (GST-3)and ten Delta-class (GST-1) glutathione S-transferases from Drosophila melanogaster, and identification of additional nine members of the Epsilon class. Biochem. J. 2003;370: 661–669
Singh SP, Coronella JA, Benes H, Cochrane BJ, Zimniak, P. Catalytic function of Drosophila melanogasterglutathione S-transferase DmGSTS1-1 (GST-2) in conjugation of lipid peroxidation end products. Eur. J. Biochem. 2001;268: 2912–2923
Udomsinprasert R, Ketterman AJ. Expression and characterisation of a novel class of glutathione S-transferase from Anopheles dirus. Insect Biochem. Mol. Biol. 2002;32: 425–433
Jirajaroenrat K, Pongjaroenkit S, Krittanai C, Prapanthadara L, Ketterman AJ. Heterologous expression and characterization of alternatively spliced glutathione- S-transferases from a single Anophelesgene. Insect Biochem. Mol. Biol. 2001;31: 867–875
Wilson TG. Drosophila melanogaster(Diptera: Drosophilidae): a model insect for insecticide resistance studies. J. Econ. Entomol. 1988;81: 22–27
Scott JG, Warren WC, Beukeboom LW, Bopp D, Clark AG, Giers SD, Hediger M, Jones AK, Kasai S, Leichter CA, Li M, Meisel RP, Minx P, Murphy TD, Nelson, DR, Reid WR, Rinkevich FD, Robertson, HM, Sackton TB, Sattelle DB, Thibaud-Nissen, F, Tomlinson C, van de Zande L, Walden KKO, Wilson RK, Liu N. Genome of the house fly, Musca domesticaL., a global vector of diseases with adaptations to a septic environment. Genome Biol. 2014;15: 466–482