Gene Symbol: Gsta4
Description: glutathione S-transferase, alpha 4
Alias: GST5.7, mGsta4, glutathione S-transferase A4, GST A4-4, GST class-alpha member 4, GSTA4-4, glutathione S-transferase 5.7
Species: mouse
Products:     Gsta4

Top Publications

  1. Engle M, Singh S, Czernik P, Gaddy D, Montague D, Ceci J, et al. Physiological role of mGSTA4-4, a glutathione S-transferase metabolizing 4-hydroxynonenal: generation and analysis of mGsta4 null mouse. Toxicol Appl Pharmacol. 2004;194:296-308 pubmed
    ..This reaction is catalyzed by specialized glutathione S-transferases (GSTs) exemplified by the murine mGSTA4-4...
  2. Ronis M, Mercer K, Gannon B, Engi B, Zimniak P, Shearn C, et al. Increased 4-hydroxynonenal protein adducts in male GSTA4-4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol. 2015;308:G403-15 pubmed publisher
    ..ethanol (EtOH) liquid diet was fed to male 129/SvJ mice (wild-type, WT) and glutathione S-transferase A4-4-null (GSTA4-/-) mice for 40 days...
  3. Xiao B, Singh S, Nanduri B, Awasthi Y, Zimniak P, Ji X. Crystal structure of a murine glutathione S-transferase in complex with a glutathione conjugate of 4-hydroxynon-2-enal in one subunit and glutathione in the other: evidence of signaling across the dimer interface. Biochemistry. 1999;38:11887-94 pubmed
    b>mGSTA4-4, a murine glutathione S-transferase (GST) exhibiting high activity in conjugating the lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) with glutathione (GSH), was crystallized in complex with the GSH conjugate of 4-HNE (GS-..
  4. Singh S, Niemczyk M, Saini D, Awasthi Y, Zimniak L, Zimniak P. Role of the electrophilic lipid peroxidation product 4-hydroxynonenal in the development and maintenance of obesity in mice. Biochemistry. 2008;47:3900-11 pubmed publisher
    ..In this paper, we report that disruption of mGsta4, a gene encoding the 4-HNE-conjugating enzyme mGSTA4-4, causes increased 4-HNE tissue levels and is accompanied by ..
  5. Ronis M, Mercer K, Engi B, Pulliam C, Zimniak P, Hennings L, et al. Global Deletion of Glutathione S-Transferase A4 Exacerbates Developmental Nonalcoholic Steatohepatitis. Am J Pathol. 2017;187:418-430 pubmed publisher
    ..steatohepatitis (NASH) by feeding a high polyunsaturated fat liquid diet to female glutathione-S-transferase 4-4 (Gsta4-/-)/peroxisome proliferator activated receptor ? (Ppara-/-) double knockout 129/SvJ mice for ..
  6. Lin L, Zheng C, Zhang L, Da C, Zhao K. 2-Aminoethoxydiphenyl borate administration into the nostril alleviates murine allergic rhinitis. Am J Otolaryngol. 2011;32:318-28 pubmed publisher
    ..Our results indicate that 2-APB treatment effectively alleviates murine AR through pleiotropic activities. ..
  7. Singh S, Niemczyk M, Saini D, Sadovov V, Zimniak L, Zimniak P. Disruption of the mGsta4 gene increases life span of C57BL mice. J Gerontol A Biol Sci Med Sci. 2010;65:14-23 pubmed publisher
    ..of 4-HNE disposal is via glutathione conjugation, in the mouse catalyzed primarily by glutathione transferase mGSTA4-4. Unexpectedly, mGsta4-null mice, in which 4-HNE detoxification is impaired, have an extended life span...
  8. Birger Y, Davis J, Furusawa T, Rand E, Piatigorsky J, Bustin M. A role for chromosomal protein HMGN1 in corneal maturation. Differentiation. 2006;74:19-29 pubmed
    ..We suggest that interaction of HMGN1 with chromatin modulates the fidelity of gene expression and affects corneal development and maturation. ..
  9. Yang Y, Huycke M, Herman T, Wang X. Glutathione S-transferase alpha 4 induction by activator protein 1 in colorectal cancer. Oncogene. 2016;35:5795-5806 pubmed publisher
    Glutathione S-transferase alpha 4 (GSTA4) is a phase II detoxifying enzyme that metabolizes electrophiles and carcinogens including 4-hydroxy-2-nonenal (4-HNE), an endogenous carcinogen that contributes to colorectal carcinogenesis...

More Information


  1. Raza H, Robin M, Fang J, Avadhani N. Multiple isoforms of mitochondrial glutathione S-transferases and their differential induction under oxidative stress. Biochem J. 2002;366:45-55 pubmed
    ..S-transferase (GST) pool in mouse liver mitochondria, and have purified three distinct forms of GST: GSTA1-1 and GSTA4-4 of the Alpha family, and GSTM1-1 belonging to the Mu family...
  2. Desmots F, Loyer P, Rissel M, Guillouzo A, Morel F. Activation of C-Jun N-terminal kinase is required for glutathione transferase A4 induction during oxidative stress, not during cell proliferation, in mouse hepatocytes. FEBS Lett. 2005;579:5691-6 pubmed
    Expression of the mouse glutathione transferase Alpha 4 (mGSTA4) has been studied during hepatocyte isolation and in cultured hepatocytes...
  3. Zimniak P, Eckles M, Saxena M, Awasthi Y. A subgroup of class alpha glutathione S-transferases. Cloning of cDNA for mouse lung glutathione S-transferase GST 5.7. FEBS Lett. 1992;313:173-6 pubmed
    ..They share a substrate specificity profile that resembles pi-class enzymes, and are active in the conjugation of lipid peroxidation products. ..
  4. Taguchi K, Maher J, Suzuki T, Kawatani Y, Motohashi H, Yamamoto M. Genetic analysis of cytoprotective functions supported by graded expression of Keap1. Mol Cell Biol. 2010;30:3016-26 pubmed publisher
    ..These results support our contention that the benefits of Nrf2 activation in acute toxicity are hormetic and that constitutive Nrf2 activation beyond a certain threshold is rather disadvantageous to long-term survival. ..
  5. Yoshihara D, Fujiwara N, Ookawara T, Kato S, Sakiyama H, Yokoe S, et al. Protective role of glutathione S-transferase A4 induced in copper/zinc-superoxide dismutase knockout mice. Free Radic Biol Med. 2009;47:559-67 pubmed publisher
    ..A gene remarkably elevated in SOD1 KO mouse kidneys was identified as the glutathione S-transferase Alpha 4 gene (Gsta4), which encodes the GSTA4 subunit...
  6. Gustafsson A, Nilsson L, Mannervik B. Hybridization of alpha class subunits generating a functional glutathione transferase A1-4 heterodimer. J Mol Biol. 2002;316:395-406 pubmed
    ..The non-additive kinetic properties of the subunits in the heterodimer therefore highlight the importance of fine-tuned subunit interactions for optimal catalytic efficiency of GST A1-1 and GST A4-4. ..
  7. Kelly V, Suzuki T, Nakajima O, Arai T, Tamai Y, Takahashi S, et al. The distal sequence element of the selenocysteine tRNA gene is a tissue-dependent enhancer essential for mouse embryogenesis. Mol Cell Biol. 2005;25:3658-69 pubmed
    ..Together, our data demonstrate that the DSE is a tissue-dependent regulatory element of tRNA(Sec) expression and that its activity is vital for sufficient tRNA(Sec) production during mouse embryogenesis. ..
  8. Sharma A, Sharma R, Chaudhary P, Vatsyayan R, Pearce V, Jeyabal P, et al. 4-Hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells. Arch Biochem Biophys. 2008;480:85-94 pubmed publisher
    ..Our results also show that the induction of p53 in tissues of mGsta4 (-/-) mice correlate with elevated levels of 4-HNE due to its impaired metabolism...
  9. Benes H, Vuong M, Boerma M, McElhanon K, Siegel E, Singh S. Protection from oxidative and electrophilic stress in the Gsta4-null mouse heart. Cardiovasc Toxicol. 2013;13:347-56 pubmed publisher
    ..By exhibiting very high levels of 4-HNE-conjugating activity, the murine glutathione transferase alpha 4 (GSTA4-4) helps regulate cellular 4-HNE levels. To examine the role of 4-HNE in vivo, we disrupted the murine Gsta4 gene...
  10. Liang A, Wang Y, Woodard L, Wilson M, Sharma R, Awasthi Y, et al. Loss of glutathione S-transferase A4 accelerates obstruction-induced tubule damage and renal fibrosis. J Pathol. 2012;228:448-58 pubmed publisher
    Glutathione transferase isozyme A4 (GSTA4) exhibits high catalytic efficiency to metabolize 4-hydroxynonenal (4-HNE), a highly reactive lipid peroxidation product that has been implicated in the pathogenesis of various chronic diseases...
  11. Krengel U, Schröter K, Hoier H, Arkema A, Kalk K, Zimniak P, et al. Crystal structure of a murine alpha-class glutathione S-transferase involved in cellular defense against oxidative stress. FEBS Lett. 1998;422:285-90 pubmed
    ..Here, we report the crystal structure of murine GSTA4-4, which is the first structure of a prototypical member of this subgroup...
  12. Kargul G, Dudekula D, Qian Y, Lim M, Jaradat S, Tanaka T, et al. Verification and initial annotation of the NIA mouse 15K cDNA clone set. Nat Genet. 2001;28:17-8 pubmed
  13. Desmots F, Rissel M, Gilot D, Lagadic Gossmann D, Morel F, Guguen Guillouzo C, et al. Pro-inflammatory cytokines tumor necrosis factor alpha and interleukin-6 and survival factor epidermal growth factor positively regulate the murine GSTA4 enzyme in hepatocytes. J Biol Chem. 2002;277:17892-900 pubmed
    ..Using confocal microscopy immunolocalization and subcellular fractionation, mGSTA4 was demonstrated in both mitochondria and cytosol and found preferentially increased in cytosol during liver ..
  14. Faria T, LaRosa G, Wilen E, Liao J, Gudas L. Characterization of genes which exhibit reduced expression during the retinoic acid-induced differentiation of F9 teratocarcinoma cells: involvement of cyclin D3 in RA-mediated growth arrest. Mol Cell Endocrinol. 1998;143:155-66 pubmed
  15. Bakin A, Stourman N, Sekhar K, Rinehart C, Yan X, Meredith M, et al. Smad3-ATF3 signaling mediates TGF-beta suppression of genes encoding Phase II detoxifying proteins. Free Radic Biol Med. 2005;38:375-87 pubmed
  16. Zimniak P, Singhal S, Srivastava S, Awasthi S, Sharma R, Hayden J, et al. Estimation of genomic complexity, heterologous expression, and enzymatic characterization of mouse glutathione S-transferase mGSTA4-4 (GST 5.7). J Biol Chem. 1994;269:992-1000 pubmed
    We have previously isolated a cDNA clone for a unique mouse lung glutathione S-transferase, mGSTA4-4 (GST 5.7) (Zimniak, P., Eckles, M. A., Saxena, M., and Awasthi, Y. C. (1992) FEBS Lett. 313, 173-176)...
  17. Medh R, Saxena M, Singhal S, Ahmad H, Awasthi Y. Characterization of a novel glutathione S-transferase isoenzyme from mouse lung and liver having structural similarity to rat glutathione S-transferase 8-8. Biochem J. 1991;278 ( Pt 3):793-9 pubmed
    ..These studies suggest that mouse GST 5.7 structurally corresponds to rat GST 8-8 and belongs to the Alpha class. ..
  18. Boerma M, Singh P, Sridharan V, Tripathi P, Sharma S, Singh S. Effects of Local Heart Irradiation in a Glutathione S-Transferase Alpha 4-Null Mouse Model. Radiat Res. 2015;183:610-9 pubmed
    Glutathione S-transferase alpha 4 (GSTA4-4) is one of the enzymes responsible for the removal of 4-hydroxynonenal (4-HNE), an electrophilic product of lipid peroxidation in cellular membranes during oxidative stress...
  19. Apidianakis Y, Que Y, Xu W, Tegos G, Zimniak P, Hamblin M, et al. Down-regulation of glutatione S-transferase ? 4 (hGSTA4) in the muscle of thermally injured patients is indicative of susceptibility to bacterial infection. FASEB J. 2012;26:730-7 pubmed publisher
    ..we demonstrate that the presence of a burn wound dramatically affects expression of both human (hGSTA4) and mouse (mGsta4) 4HNE scavengers...
  20. Curtis J, Grimsrud P, Wright W, Xu X, Foncea R, Graham D, et al. Downregulation of adipose glutathione S-transferase A4 leads to increased protein carbonylation, oxidative stress, and mitochondrial dysfunction. Diabetes. 2010;59:1132-42 pubmed publisher
    ..The primary enzymatic method for lipid aldehyde detoxification is via glutathione S-transferase A4 (GSTA4) dependent glutathionylation...
  21. Robin M, Prabu S, Raza H, Anandatheerthavarada H, Avadhani N. Phosphorylation enhances mitochondrial targeting of GSTA4-4 through increased affinity for binding to cytoplasmic Hsp70. J Biol Chem. 2003;278:18960-70 pubmed
    Recently we showed that three different isoforms of cytosolic glutathione S-transferases (GST), including GSTA4-4, are also localized in the mitochondrial compartment...
  22. Al Nimer F, Ström M, Lindblom R, Aeinehband S, Bellander B, Nyengaard J, et al. Naturally occurring variation in the Glutathione-S-Transferase 4 gene determines neurodegeneration after traumatic brain injury. Antioxid Redox Signal. 2013;18:784-94 pubmed publisher
    ..prompted us to study further if a naturally occurring genetic variation in glutathione-S-transferase alpha 4 (Gsta4) affects the outcome after TBI...
  23. Abel E, Angel J, Riggs P, Langfield L, Lo H, Person M, et al. Evidence that Gsta4 modifies susceptibility to skin tumor development in mice and humans. J Natl Cancer Inst. 2010;102:1663-75 pubmed publisher
    ..Having identified glutathione S-transferase ?4 (Gsta4) as a candidate tumor promotion susceptibility gene that mapped within the delimited region, we analyzed Gsta4-..
  24. Shearn C, Fritz K, Shearn A, Saba L, Mercer K, Engi B, et al. Deletion of GSTA4-4 results in increased mitochondrial post-translational modification of proteins by reactive aldehydes following chronic ethanol consumption in mice. Redox Biol. 2016;7:68-77 pubmed publisher
    ..A primary mechanism of reactive aldehyde detoxification by hepatocytes is through GSTA4-driven enzymatic conjugation with GSH...