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Gene Review

Gsta  -  glutathione S-transferase cluster

Mus musculus

Synonyms: GSTs, Gst-2
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Disease relevance of Gsta

  • These two murine cDNAs were subcloned into bacterial expression vectors, and enzymatically active GSTs encoded by pmGT10 (mGTmu1) or pmGT2 (mGTmu2) were purified from transformed Escherichia coli lysates [1].
  • Promoter-enhancer elements from the simian virus 40 (SV40) early-region or the mouse alpha 2(I)-collagen gene, GST cDNAs encoding the rat Ya or Yb1 isozymes, and an SV40 replicative origin (ori) were positioned in the vector to express two GSTs at high levels in the same cell [2].
  • We developed a baculovirus expression system for five of the seven cloned GSTs and determined their kinetic parameters using both thin-layer chromatography and a recently developed polymer dot-blot assay [3].
  • The acute phase response (APR) has been shown to alter expression and activity of biotransformation enzymes, such as the phase I cytochromes p450 and phase II glutathione S-transferases (GSTs) [4].
  • In conventional as well as in GF mice the mu and pi class GSTs showed reduced intestinal expression when colitis was induced [5].

High impact information on Gsta

  • Furthermore, in highlighting the control of apoptosis by GSTs, these data provide new insights for analyzing the complex mechanisms of hepatoprotection [6].
  • This role of GSTs was further assessed by showing that their high expression level was tightly associated with inhibition of ASK1 activity in Me(2)SO-protected hepatocytes [6].
  • Based on sequence homology and protein activity we conclude that p28 acts as a small stress response protein, likely involved in cellular redox homeostasis, and belongs to a family of GST-like proteins related to class theta GSTs [7].
  • As the rGSTM5, mGSTM5, and hGSTM3 subunits are structurally more closely related to each other than they are to other Mu GSTs, it is proposed that they be considered a functionally distinct and separate subfamily within class Mu [8].
  • All three GSTs of this subclass have N- and C-terminal extensions with C-terminal cysteine residues, but the two penultimate amino acids near the C terminus are divergent in the three species [8].

Chemical compound and disease context of Gsta

  • One of the major mechanisms of protection against carcinogenesis, mutagenesis, and other forms of toxicity mediated by carcinogens is the induction of enzymes involved in their metabolism, particularly phase 2 enzymes such as glutathione S-transferases (GSTs), UDP-glucuronosyl transferases, and quinone reductases [9].
  • CONCLUSION: These data collectively indicate that expression of GSTs is increased in epithelial cells in proximal tubules even at the early stage of diabetes, probably in response to oxidative stress triggered by hyperglycemia or other toxic effects of glucose [10].

Biological context of Gsta

  • These genes were glutathione S-transferase Ya subunit (Gsta), the T3 gamma subunit, the low density lipoprotein receptor, and the Ets-1 oncogene [11].
  • Pi-class glutathione S-transferases (GSTs) play an important role in the detoxification of chemical toxins and mutagens and are implicated in neoplastic development and drug resistance [12].
  • These data show that the Yb2 subunit is distinct from the GSTs that are encoded by the cDNAs that have been cloned from mouse liver cDNA libraries but possesses identity with the protein that is encoded by pmGT2, a cDNA isolated from a mouse fibroblast cell line by Townsend, Goldsmith, Pickett & Cowan [(1989) J. Biol. Chem. 264. 21582-21590] [13].
  • Introduction of such mutations may have contributed to the biological evolution of GST isoenzymes with altered substrate specificities and may also find use in the engineering of GSTs for novel functions [14].
  • The deduced amino acid sequence of mGSTM7, which comprises of 218 amino acid residues, exhibited about 67-78% identity with other Mu class murine GSTs [15].

Anatomical context of Gsta

  • The three mu-class GSTs of testis and ovary arise from the dimeric combinations of two subunits whose N-terminal sequences determined up to 24 residues were similar to those of mouse liver GST subunits mu 1 and mu 2 [16].
  • The denitrosation of a novel nitrosourea, 1-(2-chloroethyl)-3-[(2-dimethylaminosulfonyl)-ethyl]-1-nitrosoure a, tauromustine (TCNU), has been investigated in liver cytosol from various species and with a pool of cytosolic rat liver glutathione transferases (GSTs) [17].
  • Our study, for the first time, demonstrates the presence in mitochondria of multiple forms of GSTs that show molecular properties similar to those of their cytosolic counterparts [18].
  • The Gal/GalNAc/GlcNAc-6-O-sulfotransferases (GSTs) are a recently discovered family of carbohydrate sulfotransferases that share significant sequence homology at the amino acid level and mediate a number of different biological processes such as leukocyte adhesion at sites of chronic inflammation [3].
  • This is the first report of localization of GSTs in mouse brain and of GST in myelin [19].

Associations of Gsta with chemical compounds

  • The cytosolic glutathione S-transferases (GSTs, EC are a superfamily of dimeric isoenzymes which catalyze the conjugation of electrophilic substrates with glutathione [1].
  • Induction of glutathione S-transferases (GSTs) is believed to represent an important mechanism whereby butylated hydroxyanisole inhibits chemical carcinogenesis [13].
  • The induction of GSTs by phenobarbital in rats increased the denitrosation of TCNU similar to the activities found towards CDNB and tSBO as substrates [17].
  • In a 6 week dose-response study of select NOCs and 7,8-benzoflavone (a potent P4501 inhibitor that had little effect on GSTs), DMBA-DNA adduct formation was inhibited by 0, 43 and 24% in the limettin groups; by 26, 26 and 69% in the isopimpinellin groups; and by 80, 96 and 97% in the 7,8- benzoflavone groups at 35, 70 and 150 mg/kg, respectively [20].
  • Even though the levels of various hepatic GST isoenzymes were significantly increased upon curcumin feeding, maximum induction was noticed for the pi class isoenzyme (mGSTP1-1), which among murine hepatic GSTs is highly efficient in the detoxification of (+)-anti-BaPDE [21].

Regulatory relationships of Gsta

  • The soluble hepatic GSTs expressed by mice fed on normal diets are all homodimers comprising Ya3 (Mr 25,800), Yb1 (Mr 26,400) and Yf (Mr 24,800) subunits [13].

Other interactions of Gsta

  • The sequence data also show that the cDNA encoding the mouse Yb5 subunit has not, to date, been cloned, and the relationship between this subunit and Mu-class GSTs in other species that possess a blocked N-terminus (e.g. rat GST YoYo) is discussed [13].

Analytical, diagnostic and therapeutic context of Gsta

  • Cells expressing the recombinant GSTs were viably sorted by flow cytometry on the basis of a GST-catalyzed conjugation of glutathione to monochlorobimane [2].
  • After animals were force-fed these compounds, tissue GSTs were purified and individual subunits resolved by HPLC and identified on the basis of mass spectrometry (ESI MS) and immunoreactivity data [22].
  • Three forms of GST were isolated by means of affinity chromatography and f.p.l.c. The examination of protein profiles and enzymic activities with specific substrates showed that the three GSTs correspond to those found in control animals, i.e. GSTs MI, MII and MIII [23].
  • Real-time PCR (TaqMan) methods were used for quantitative estimations of relative amounts of the mRNAs encoding the GSTs [22].
  • The mitochondrial localization of these multiple GSTs was confirmed using a combination of immunoblot analysis, protease protection assay, enzyme activity, N-terminal amino acid sequencing, peptide mapping and confocal immunofluorescence analysis [18].


  1. Isolation, characterization, and expression in Escherichia coli of two murine Mu class glutathione S-transferase cDNAs homologous to the rat subunits 3 (Yb1) and 4 (Yb2). Townsend, A.J., Goldsmith, M.E., Pickett, C.B., Cowan, K.H. J. Biol. Chem. (1989) [Pubmed]
  2. Expression of tandem glutathione S-transferase recombinant genes in COS cells for analysis of efficiency of protein expression and associated drug resistance. Manoharan, T.H., Welch, P.J., Gulick, A.M., Puchalski, R.B., Lathrop, A.L., Fahl, W.E. Mol. Pharmacol. (1991) [Pubmed]
  3. Characterization and mutagenesis of Gal/GlcNAc-6-O-sulfotransferases. Grunwell, J.R., Rath, V.L., Rasmussen, J., Cabrilo, Z., Bertozzi, C.R. Biochemistry (2002) [Pubmed]
  4. Characterization of the mouse olfactory glutathione S-transferases during the acute phase response. Weech, M., Quash, M., Walters, E. J. Neurosci. Res. (2003) [Pubmed]
  5. Selective expression of detoxifying glutathione transferases in mouse colon: effect of experimental colitis and the presence of bacteria. Edalat, M., Mannervik, B., Axelsson, L.G. Histochem. Cell Biol. (2004) [Pubmed]
  6. Liver protection from apoptosis requires both blockage of initiator caspase activities and inhibition of ASK1/JNK pathway via glutathione S-transferase regulation. Gilot, D., Loyer, P., Corlu, A., Glaise, D., Lagadic-Gossmann, D., Atfi, A., Morel, F., Ichijo, H., Guguen-Guillouzo, C. J. Biol. Chem. (2002) [Pubmed]
  7. The cloning and characterization of a new stress response protein. A mammalian member of a family of theta class glutathione s-transferase-like proteins. Kodym, R., Calkins, P., Story, M. J. Biol. Chem. (1999) [Pubmed]
  8. Rationale for reclassification of a distinctive subdivision of mammalian class Mu glutathione S-transferases that are primarily expressed in testis. Rowe, J.D., Patskovsky, Y.V., Patskovska, L.N., Novikova, E., Listowsky, I. J. Biol. Chem. (1998) [Pubmed]
  9. Role of phase 2 enzyme induction in chemoprotection by dithiolethiones. Kwak, M.K., Egner, P.A., Dolan, P.M., Ramos-Gomez, M., Groopman, J.D., Itoh, K., Yamamoto, M., Kensler, T.W. Mutat. Res. (2001) [Pubmed]
  10. Increased expression of glutathione S-transferase in renal proximal tubules in the early stages of diabetes: a study of type-2 diabetes in the Akita mouse model. Fujita, H., Haseyama, T., Kayo, T., Nozaki, J., Wada, Y., Ito, S., Koizumi, A. Exp. Nephrol. (2001) [Pubmed]
  11. A molecular genetic linkage map of mouse chromosome 9 with regional localizations for the Gsta, T3g, Ets-1 and Ldlr loci. Kingsley, D.M., Jenkins, N.A., Copeland, N.G. Genetics (1989) [Pubmed]
  12. Isolation and characterization of two mouse Pi-class glutathione S-transferase genes. Bammler, T.K., Smith, C.A., Wolf, C.R. Biochem. J. (1994) [Pubmed]
  13. Hepatic glutathione S-transferases in mice fed on a diet containing the anticarcinogenic antioxidant butylated hydroxyanisole. Isolation of mouse glutathione S-transferase heterodimers by gradient elution of the glutathione-Sepharose affinity matrix. Hayes, J.D., Kerr, L.A., Peacock, S.D., Cronshaw, A.D., McLellan, L.I. Biochem. J. (1991) [Pubmed]
  14. The high activity of rat glutathione transferase 8-8 with alkene substrates is dependent on a glycine residue in the active site. Björnestedt, R., Tardioli, S., Mannervik, B. J. Biol. Chem. (1995) [Pubmed]
  15. Cloning and expression of a novel Mu class murine glutathione transferase isoenzyme. Guo, J., Zimniak, L., Zimniak, P., Orchard, J.L., Singh, S.V. Biochem. J. (2002) [Pubmed]
  16. Purification and characterization of glutathione S-transferase of murine ovary and testis. Awasthi, S., Singhal, S.S., Srivastava, S.K., Awasthi, Y.C. Arch. Biochem. Biophys. (1993) [Pubmed]
  17. Measurement and characterization of the denitrosation of tauromustine and related nitrosoureas by glutathione transferases in liver cytosol from various species. Tuvesson, H., Gunnarsson, P.O., Seidegård, J. Carcinogenesis (1993) [Pubmed]
  18. Multiple isoforms of mitochondrial glutathione S-transferases and their differential induction under oxidative stress. Raza, H., Robin, M.A., Fang, J.K., Avadhani, N.G. Biochem. J. (2002) [Pubmed]
  19. A pi form of glutathione-S-transferase is a myelin- and oligodendrocyte-associated enzyme in mouse brain. Tansey, F.A., Cammer, W. J. Neurochem. (1991) [Pubmed]
  20. Naturally occurring coumarins inhibit 7,12-dimethylbenz[a]anthracene DNA adduct formation in mouse mammary gland. Prince, M., Campbell, C.T., Robertson, T.A., Wells, A.J., Kleiner, H.E. Carcinogenesis (2006) [Pubmed]
  21. Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. Singh, S.V., Hu, X., Srivastava, S.K., Singh, M., Xia, H., Orchard, J.L., Zaren, H.A. Carcinogenesis (1998) [Pubmed]
  22. Selective expression of glutathione S-transferase genes in the murine gastrointestinal tract in response to dietary organosulfur compounds. Andorfer, J.H., Tchaikovskaya, T., Listowsky, I. Carcinogenesis (2004) [Pubmed]
  23. Effects of inducers of drug metabolism on basic hepatic forms of mouse glutathione transferase. Di Simplicio, P., Jensson, H., Mannervik, B. Biochem. J. (1989) [Pubmed]
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