Glutathione-transferase alpha

Glutathione-transferase alpha (GST-a) protects cells by catalyzing the detoxification of xenobiotics and carcinogens. GST-a was recently found to be of diagnostic value in renal tumors. On the basis of cDNA microarray findings, immunohistochemical studies have so far shown GST-a to be highly expressed in CCRCC (90%) but not in ChRCC or oncocytomas and only occasionally in PRCC. 

Di Ilio C, Sacchetta P, lannarelli V, et al. 1995. Binding of pesticides to alpha, mu and pi class glutathione transferase. Toxicol Lett 76 173-177. 

Wadleigh RW, Yu SJ (1987) Glutathione transferase activity of fall armyworm larvae toward alpha-, beta-unsaturated carbonyl allelochemicals and its induction by allelochemicals. Insect Biochem 17 759-764... 

Protein cross-links may be also produced in reaction of 4-hydroxynonenal with lysine, histidine, serine, and cysteine residues, primarily via Michael addition (J5, R7, U8). These reactions occur spontaneously, but also may be catalyzed by certain glutatione 5-transferases. The glutathione transferase A4-4, which unlike other alpha-class glutathione transferases, shows high catalytic activity toward lipid peroxidation products such as 4-hydroxynon-2-enal, is the key enzyme for these reactions (B31). Products of protein coupling with aldehydes secondary to lipid peroxidation have a specific fluorescence, which can herald the protein oxidative modification process (CIO). 

Yang, X. (2005). Overexpression of glutathione S-transferase alpha in clear cell renal cell carcinoma. Am. J. Clin. Pathol. 123, 421-429. 

Jemstrom, B, Mariner, H., Meyer, D. J., and Ketterer, B. (1985). Glutathione Conjugation of the Carcinogenic and Mutagenic Electrophile (+/—)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-oxy-7,8,9,10-tetra hydrobenzo[a]pyrene Catalyzed by Purified Rat Liver Glutathione Transferases, Carcinogenesis, 6 85-93. 

Rozell B, Flansson FIA, Guthenberg C, Tahir MK, MannervikB. Glutathione transferases of classes alpha, mu and pi show selective expression in different regions of rat kidney. Xenobiotica (1993) 23(8) 835-849. 

Glutathione GSTA1 Glutathione S-transferase alpha 1 6pl2.1... 

Branten AJ, Mulder TP, Peters WH, Assmann KJ, Wetzels JF (2000) Urinary excretion of glutathione S transferases alpha and pi in patients with proteinuria reflection of the site of tubular injury. Nephron 85(2) 120-126, doi 45644... 

Sakai, M., Matsushima-Hibiya, Y., Nishizawa, M., and Nishi, S. (1995) Suppression of rat glutathione transferase P expression by peroxisome proliferators interaction between Jun and peroxisome proliferator-activated receptor alpha. Cancer Res. 55, 5370-5376. 

AlO. Alin, P., Jensson, H., Cederlund, E., Jomvall, H., and Mannervik, B., Cytosolic glutathione transferases from rat liver. Primary structure of class alpha glutathione transferase 8-8 and characterization of low-abundance class Mu glutathione transferases. Biochem. J. 261, 531-539 (1989). 

B26. Berhane, K., and Mannervik, B., Inactivation of the genotoxic aldehyde acrolein by human glutathione transferases of classes alpha, mu, and pi. Mol. Pharmacol 37, 251-254 (1990). 

The glutathione transferase (GST) comprises multifunctional proteins coded by a multigene family. These enzymes are both cytosolic and microsomal and function as homodimers and heterodimers. They exist as four classes in mammals. The human enzymes comprise the following dimers Al-1, Al-2, A2-2, A3-3 (alpha class), Mla-la, Mla-lb, Mlb-lb, Mla-2, M2-2, M3-3 (mu class), Pl-1 (pi class), Tl-1 (theta class), and three microsomal enzymes (MIC). The GST Al-1 and Al-2 are also known as ligandin when they act as binding or carrier proteins, a property also displayed by Mla-la, Mlb-lb and also by GSH (pi class). 

The glutathione transferases are soluble dimeric proteins that are composed of identical subunits, although some forms are heterodimers. These enzymes are present in most tissues and are primarily cytosolic (approximately 95%), although a small percentage are found in the endoplasmic reticulum (approximately 5%). The cytosolic glutathione S-transferases (GSTs) are divided into six families or classes alpha, kappa, mu, pi, sigma, and theta. The alpha, mu, and pi GST classes are primarily responsible for most of the catalytic activity associated with liver detoxication of xenobiotics. 

Clapper ML, Everley EC, Strobel LA, Townsend AJ, Engstrom PF. Coordinate induction of glutathione S-transferase alpha, mu, and pi expression in murine liver after a single administration of oltipraz. Mol Pharmacol 1994 45 469-474. 

Tetlow N, Liu D, Board P. Polymorphism of human Alpha class glutathione transferases. Pharmacogenetics 2001 11(7) 609-617. 

Tong Z, Board PG, Anders MW. Glutathione transferase zeta-catalyzed biotransformation of dichloroacetic acid and other alpha-haloacids. Chem Res Toxicol 1998 11(11) 1332-1338. 

BERHANE, K., WIDERSTEN, M., ENGSTROM, A., KOZARICH, J.W., MANNERVIK, B., Detoxication of base propenals and other alpha, beta-unsaturated aldehyde products of radical reactions and lipid peroxidation by human glutathione transferases, Proc. Natl. Acad. Sci. USA, 1994, 91, 1480-1484. 

Caccuii AM, Antonini G et al (1999) Proton release on binding of glutathimie to alpha, mu and delta class glutathione transferases. Biochem J 344(Pt 2) 419-425... 

Cameron, A.D., Sinning, I., L Hermite, G., Olin, B., Board, P.G., Mannervik, B., and Jones, T.A. 1995. Structural analysis of human alpha-class glutathione transferase Al-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate. Structure, 3, 717-727. 

Krishna R.N., Getchell T.V. and Getchell M.L. (1994). Differential expression of alpha-class, mu-class, and pi-class of glutathione S-transferases in chemosensory mucosae of rats during development. J Neurosci Res 39, 243-259. 

Sherratt, P.J., Pulford, D.J., Harrison, D.J., Green, T. Hayes, J.D. (1997) Evidence that human class theta glutathione S-transferases Tl-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse. Comparison of the tissue distribution of GST Tl-1 with that of classes alpha, mu and pi GST in human. Biochem. J., 326. 837-846... 

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