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Gene Review

Gsta4  -  glutathione S-transferase alpha 4

Rattus norvegicus

Synonyms: GST 8-8, GST A4-4, GST K, GST Yk, Glutathione S-transferase Yk, ...
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Disease relevance of Gsta4


Psychiatry related information on Gsta4

  • Alterations in GSH and other GSH-related enzymes at 3 and 10 days support the concept that--upon AA exposure--aortic defense mechanisms respond early and induction of GSH biosynthesis and rat GST8-8 occur to alleviate the toxic effects of acrolein, a major, genotoxic product of AA metabolism [2].

High impact information on Gsta4

  • All alpha-class GST antibodies studied were reactive, to various degrees, with astrocytes and choroid plexus; however, ependymal cells of the subventricular zones were immunonegative. alpha-class GST 8-8 (YkYk) immunoreactivity was specifically localized to endothelial cells and/or astrocytic end feet associated with blood vessels [3].
  • Transient transfection of COS cells with CYP2E1 cDNA caused a similar accumulation of CYP2E1 and GST A4-4 in mitochondria and increased production of mitochondrial ROS [4].
  • These studies suggest that mouse GST 5.7 structurally corresponds to rat GST 8-8 and belongs to the Alpha class [5].
  • In general, GST 7-7 was better than GST 8-8 in utilizing these analogues as substrates, and glycyl analogues were better than gamma-glutamyl analogues as both substrates and inhibitors [6].
  • The 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-induced oxidative damage was apparent in the microsomal fraction of brain, lung, and liver, and it also increased 4-hydroxynonenal specific GST A4-4 activity in the brain and lung mitochondrial matrix fraction [1].

Biological context of Gsta4

  • We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3 [7].
  • Gsta4 expression was strongly correlated with the gene dose of var3, with approximately 60% of the variance in expression accounted for by genotype at this locus [7].
  • The presence of GST8-8 in the vasculature, which is constantly exposed to products of lipid peroxidation, and its induction by AA, suggest that GST8-8 plays a key role in protecting blood vessels against oxidative stress and hence, may be involved in the atherogenic process [2].

Anatomical context of Gsta4


Associations of Gsta4 with chemical compounds


Analytical, diagnostic and therapeutic context of Gsta4

  • Western blot of purified total GSTs using antibodies against rec-mGSTA4-4 revealed a single band at 25 kDa, confirming the presence of a GST isozyme immunologically similar to rat GST8-8, which is known to utilize alpha,beta-unsaturated carbonyls as preferred substrates [12].


  1. Preferential effects of nicotine and 4-(N-methyl-N-nitrosamine)-1-(3-pyridyl)-1-butanone on mitochondrial glutathione S-transferase A4-4 induction and increased oxidative stress in the rat brain. Bhagwat, S.V., Vijayasarathy, C., Raza, H., Mullick, J., Avadhani, N.G. Biochem. Pharmacol. (1998) [Pubmed]
  2. Glutathione S-transferase 8-8 is localized in smooth muscle cells of rat aorta and is induced in an experimental model of atherosclerosis. Misra, P., Srivastava, S.K., Singhal, S.S., Awasthi, S., Awasthi, Y.C., Boor, P.J. Toxicol. Appl. Pharmacol. (1995) [Pubmed]
  3. Glutathione S-transferase isoenzymes in rat brain neurons and glia. Johnson, J.A., el Barbary, A., Kornguth, S.E., Brugge, J.F., Siegel, F.L. J. Neurosci. (1993) [Pubmed]
  4. Elevated mitochondrial cytochrome P450 2E1 and glutathione S-transferase A4-4 in streptozotocin-induced diabetic rats: tissue-specific variations and roles in oxidative stress. Raza, H., Prabu, S.K., Robin, M.A., Avadhani, N.G. Diabetes (2004) [Pubmed]
  5. Characterization of a novel glutathione S-transferase isoenzyme from mouse lung and liver having structural similarity to rat glutathione S-transferase 8-8. Medh, R.D., Saxena, M., Singhal, S.S., Ahmad, H., Awasthi, Y.C. Biochem. J. (1991) [Pubmed]
  6. Interaction of rat glutathione S-transferases 7-7 and 8-8 with gamma-glutamyl- or glycyl-modified glutathione analogues. Adang, A.E., Meyer, D.J., Brussee, J., Van der Gen, A., Ketterer, B., Mulder, G.J. Biochem. J. (1989) [Pubmed]
  7. Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity. Björk, K., Saarikoski, S.T., Arlinde, C., Kovanen, L., Osei-Hyiaman, D., Ubaldi, M., Reimers, M., Hyytiä, P., Heilig, M., Sommer, W.H. FASEB J. (2006) [Pubmed]
  8. Rat GST 8-8 is expressed predominantly in myeloid origin cells infiltrating the gravid uterus. Awasthi, S., Singhal, S.S., Srivastava, S.K., Chaubey, M., Piper, J.T., Zimniak, P., Yallampalli, C., Rajaraman, S., Awasthi, Y.C. Int. J. Biochem. Cell Biol. (1997) [Pubmed]
  9. Glutathione S-transferase 8-8 expression is lower in alcohol-preferring than in alcohol-nonpreferring rats. Liang, T., Habegger, K., Spence, J.P., Foroud, T., Ellison, J.A., Lumeng, L., Li, T.K., Carr, L.G. Alcohol. Clin. Exp. Res. (2004) [Pubmed]
  10. Metabolism of 4-hydroxynonenal by rat Kupffer cells. Luckey, S.W., Petersen, D.R. Arch. Biochem. Biophys. (2001) [Pubmed]
  11. Attenuation of 4-hydroxynonenal-induced cataractogenesis in rat lens by butylated hydroxytoluene. Srivastata, S.K., Awasthi, S., Wang, L., Bhatnagar, A., Awasthi, Y.C., Ansari, N.H. Curr. Eye Res. (1996) [Pubmed]
  12. The role of glutathione S-transferases as a defense against reactive electrophiles in the blood vessel wall. He, N.G., Awasthi, S., Singhal, S.S., Trent, M.B., Boor, P.J. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
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