Full Text:   <2883>

CLC number: Q5

On-line Access: 

Received: 2005-01-13

Revision Accepted: 2005-03-15

Crosschecked: 0000-00-00

Cited: 6

Clicked: 5703

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2005 Vol.6 No.8 P.759-769


Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene


Affiliation(s):  Department of Biochemistry, Sri Venkateswara University, Tirupati 517 502, AP, India

Corresponding email(s):   Thyagarajuk_1999@yahoo.com

Key Words:  Glutathione transferases, Testis, Brain, Phenobarbitol, &beta, -Methylcholanthrene

THYAGARAJU K., HEMAVATHI B., VASUNDHARA K., RAO A.D., DEVI K.N.. Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene[J]. Journal of Zhejiang University Science B, 2005, 6(8): 759-769.

@article{title="Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene
%J Journal of Zhejiang University SCIENCE B
%V 6
%N 8
%P 759-769
%@ 1673-1581
%D 2005
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2005.B0759

T1 - Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene
A1 - RAO A.D.
A1 - DEVI K.N.
J0 - Journal of Zhejiang University Science B
VL - 6
IS - 8
SP - 759
EP - 769
%@ 1673-1581
Y1 - 2005
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2005.B0759

A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and b-Methylcholanthrene (MC). glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Y&beta; and Yδ in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or &beta;-Methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Yδ of π class was expressed on PB treatment and Yc of α class and Y&beta; of μ class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and &beta;-Methylcholanthrene stress.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Abramovitz, M., Homma, H., Ishigaki, S., Tancey, F., Cammer, W., Listowsky, I., 1988. Characterization and localization of glutathione S-transferase in rat brain. J. Neurochem., 50:50-57.

[2] Aliya, S., Reddanna, P., Thyagaraju, K., 2003. Does glutathione S-transferase pi a carcinogenic marker? Molecular and Cellular Biochemistry, 253:313-318.

[3] Awasthi, Y., Singh, S.V., 1985. Subunit structure of human and rat glutathione S-transferases. Comp. Biochem. Physiol., 82B:17-23.

[4] Beckett, G.J., Hayes, J.D., 1993. Glutathione S transferases: Biomedical applications. Adv. Clin. Chem., 30:281-380.

[5] Beckett, G.J., Hussey, A.J., Laing, I., Howie, A.F., Hayes, J.D., Strange, R.C., Faulder, C.G., Hume, R., 1989. Measurements of glutathione S transferases B1 in plasma after birth asphyxia: An early indication of hepatocellular damage. Clin. Chem., 35:995-999.

[6] Board, P.G., Coggan, M., Chelvanayagam, G., Easteal, S., Jermiin, L.S., Schulte, G.K., Danley, D.B., Hoth, L.R., Griffor, M.C., Kamath, A.V., Rosner, M.H, Chrunyk, B.A., Perregaux, D.B., Gabel, C.A., Geoghegan, K.F., Pandit, J., 2000. Identification, characterization and crystal structure of the omega class glutathione transferases. J. Biol. Chem., 275:24798-24806.

[7] Chang, M., Hong, Y., Burgess, J.R., Tu, C.P.D., Reddy, C.C., 1987. Isozyme specificity of rat liver glutathione S-transferases in the formation of PGF and PGE2 from PGH2. Arch. Biochem. Biophy., 259:548-557.

[8] Clifton, G., Kaplowitz, N., 1978. Effect of dietary phenobarbitol, 3,4-benzopyrene and 3-methlycholanthrene on hepatic, intestinal and renal glutathione S-transferase activity in the rat. Biochem. Pharmacol., 27:1284-1287.

[9] Coles, B., Ketterer, B., 1990. The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit. Rev. Biochem. Mol. Biol., 25:47-70.

[10] Devi, K.N., Reddy, C.C., Raveendra, A., Thyagaraju, K., 2002a. Effect of β-methyl cholanthrene on glutathione S-transferases of rat testis. Current Sci., 82:1282-1287.

[11] Devi, K.N., Hemavathi, B., Aliya, S., Raveendra, A., Thyagaraju, K., 2002b. A comparative study on the effect of PB and MC on glutathione S transferases of rat testis. J. Biochem. Molbiol. Biophys., 6(6):373-378.

[12] Dragan, Y.P., Singh, J., Pitit, H.C., 1996. Effect of separate and combined administration of mestranol and PB on glutathione S transferases of rat testis. Journal of Biochemistry, Molecular Biology and Biophysics, 6:373-378.

[13] Feinfeld, D.A., Fleischner, G.M., Arias, I.M., 1981. Urinary ligandin and glutathioen S tarnsferases in Gentamicin induced nephrotoxicity in the rat. Clin. Sci., 61:123-125.

[14] Guthenberg, C., Morgenstern, R., Depierre, J.W., Mannervik, B., 1980. Induction of GSTs A, B and C in rat liver cytosol by trans stillbene oxide. Biochem. Biophys. Acta, 631:1-10.

[15] Guthenberg, C., Astrand, I.M., Alin, P., Mannervik, B., 1983. Glutathione S-transferase in rat testis. Acta. Chem. Scand. Ser., B37:261.

[16] Habig, W.H., Jakoby, W.B., 1981. Assays for differentiation of glutathione S-transferases. Methods Enzymol., 77:398-405.

[17] Habig, W.H., Pabst, M.J., Jakoby, W.B., 1974. Glutathione S-transferase the firstenzymatic step in mercapturic acid formation. J. Biol. Chem., 249:7130-7139.

[18] Hayes, J.D., Mantle, T.J., 1986. Inhibition of hepatic and extrahepatic glutathione S-transferases by primary and secondary bile acids. Biochem. J., 233:779-788.

[19] Hayes, P.C., Portman, B., Aldis, P.M., Williams, R., Hayes, J.D., 1987. Glutathione S-Transferases and Human Pathology. In: Mantle, T.J., Pickett, C.B., Hayes, J.D. (Eds.), Glutathione S-transferases and Carcinogenesis. Taylor and Francis, London, p.175-187.

[20] Hayes, P.C., Hussey, A.J., Keating, J., Bouchier, I.A.D., Williams, R., Beckett, G.J., Hayes, J.D., 1988. Glutathione S transferase level in autoimmune chronic active hepatitis: A more sensitive index of hepatocellular damage than aspartate transaminase. Clin. Chem. Acta, 172:211-216.

[21] Hiratsuka, A., Sebata, N., Kswashima, K., Okuda, H., Ogura, K., Watabe, T., Satoh, K., Hatayama, I., Tsuchida, S., Ishikawa, T., Sat, K., 1990. A new class of rat glutathione S transferase Yrs-Yrs inactivating reactive sulphate esters as metabolites of carcinogenic aryl methanols. J. Biol. Chem., 265:11973-11981.

[22] Howie, A.W., Patrick, B.M., Fisher, A., Collier Frier, B.M., Beckett, G.J., 1989. Plasma hepatic glutathione S tarnsferase concentrations after insulin induced hypoglycemia in normal subjects and diabetic patients. Diabetic Med., 6:224-227.

[23] Kaplowitz, N., Kuhlen Kamp, J., Clifton, G., 1975. Drug induction of hepatic glutathione S-transferase in male and female rats. Biochem. J., 146:351-356.

[24] Ketterer, B., Tan, K.H., Meyer, D.J., Coles, B., 1987. Glutathione S-Transferases and Carcinogenesis. In: Mantle, T.J., Pickett, C.B., Hayes, J.D. (Eds.), Taylor and Francis. London, p.149-164.

[25] Kitahara, A., Satoh, K., Nishimura, K., Ishikawa, T., Ruike, K., Sato, K., Tsuda, H., Ito, N., 1984. Changes in molecular forms of rat hepatic glutathione S transferase durin chemical hepato carcinogenesis. Cancer Res., 44:2698-2703.

[26] Klys, H.S., Whillis, D., Howard, G., Harrison, D.J., 1992. Glutathione S-transferase expression in human testis and testicular germ cell neoplasia. Br. J. Cancer, 66:589-593.

[27] Laemmli, U.K., 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 227:680-685.

[28] Li, N., Reddanna, P., Thyagaraju, K., Reddy, C.C., Tu, C.P.D., 1986. Expression of glutathione S-transferases in rat brain. J. Biol. Chem., 261:7596-7599.

[29] Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., 1951. Protein measurement with Folin phenol reagent. J. Biol. Chem., 193:265-275.

[30] Mannervik, B., Danielson, U.H., 1988. Glutathione S-transferases, structure and catalytic activity. CRC. Crit. Rev. Biochem. Mol. Biol., 23:283-337.

[31] Mannervik, B., Awasthi, Y.C., Board, P.G., Hayes, J.D., Dillio, C., Ketterer, B., 1992. Nomenclature of human glutathione transferases. Biochem. J., 282:305-306.

[32] Meyer, D.J., Beale, D., Tan, K.H., Cole, B., Ketterer, B., 1985. Glutathione S-transferases in primary rat hepatomas: The isolation of a form with glutathione peroxidase activity. FEBS Lett., 184:139-143.

[33] Meyer, D.J., Coles, B., Pemble, S.E., Gilmore, K.S., Fraser, G.M., Ketterer, B., 1991. Theta, a new class of glutathione S-transferases purified from rat and man. Biochem. J., 274:409-414.

[34] Morton, M.R., Bayney, R.M., Pickett, C.B., 1990. Isolation and characterization of the rat GSTs-Yb subunit gene. Archives of Biochemistry and Biophysics, 277:56-60.

[35] Ouchterlony, O., 1966. Handbook of Immunodiffusion and Immuno Electrophoresis. 2nd Ed., An Arbore Publishers, Ann Arbor.

[36] Rabahi, F., Brule, S., Sirois, J., Beckers, J.F., Silversides, D.W., Lussier, J.G., 1999. High expression of bovine alpha glutathione S-transferase (GSTA1 and GSTA2) subunits is mainly associated with steroidogenically active cells and regulated by gonadotrophins in bovine ovarian follicles. Endocrinology, 140:3507-3517.

[37] Reynaud, S., Marionnet, D., Taysse, L., Duchiron, C., Deschaux, P., 2002. The effects of 3-methylcholanthrene on macrophage respiratory burst and bio-transformation activities in the common carp (Cyprinus carpio L.). Fish Shellfish Immunol, 12:17-34.

[38] Rowet, J.D., Patskovisky, Y.V., Patskovska, L.N., Novikova, E., Listowisky, I., 1998. Rationale for reclassification of a distinctive subdivision of mammalian class mu glutathione S-transferases that are primarily expressed in testis. J. Biol. Chem., 273:9593-9601.

[39] Rushmore, T.H., Sharma, R.N.S., Roomi, M.W., Harris, L., Satoh, K., Sato, K., Murray, R.K., Farber, E., 1987. Identification of a characteristic cytosolic poly peptide of rat preneoplastic hepatocyte nodules as placental glutathione S transferase. Biochem. Biophys. Res. Commun, 143:98-103.

[40] Sato, K., Kitahara, A., Satoh, Y., Ishikawa, T., Tatematsu, M., Ito, N., 1984. The placental form of glutathione S transferase as a new marker protein for preneoplasia in rat chemical carcinogenesis, Gann. Jpn. J. Cancer Res., 75:199-202.

[41] Satoh, K., Kitahara, A., Soma, Y., Inaba, Y., Hatayama, I., Sato, K., 1985. Purification, induction and distribution of placental glutathione S-transferases: A new marker enzyme for preneoplastic cells in the rat chemical hepato carcinogenesis. Proc. Natl. Acad. Sci. USA, 82:3964-3968.

[42] Singh, S.V., Saunders, M.O., Moller, P.C., Haber, B., Aswasthi, Y.C., 1987. Comparative studies on the isoenzymes of glutathione S-transferase of rat brain and other tissues. Comp. Biochem. Physiol., 86B:73-81.

[43] Tahir, M.K., Mannervik, B., 1986. Simple inhibition studies for distinction between homodimeric and heterodimeric isoenzymes of glutathione S transferases. J. Biol. Chem., 261:1048-1051.

[44] Thyagaraju, K., Reddanna, P., Nirmala Devi, K., Hildenbrandt, G.R., Reddy, C.C., 1994. Structural multiplicity of glutathione S-transferases. J. Parasit. Appl. Anim. Biol., 3(1):23-29.

[45] Thyagaraju, K., Devi, K.N., Hildenbrandt, G.R., Reddy, C.C., 1996. Purification and characterization of 12 forms of rat brain GSTs. J. Parasitol. Appl. Animal. Biol., 5(1):33-48.

[46] Thyagaraju, K., Vasundhara, K., Hemavathi, B., Uma, A., Devi, K.N., 2004. Effect of phenobarbitol on the induction of glutathione S-transferases in rat testis. Reproductive Biomedicine Online, 8(1):68-74.

[47] Towbin, H.T., Staehelin, J., Gordon, J., 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications. Proc. Natl. Acad. Sci. USA, 7614:4350-4354.

[48] Trull, A.K., Facey, S.P., Rees, G.W., Wight, D.P.D., Nobile-Jamieson, G., Joughin, C., Friend, P.J., Alexander, G.J.M., 1994. Serum alpha-glutathione S transferase: A sensitive marker of hepatocellular damage associated with acute liver allograft rejection. Transplantation, 58:1345-1351.

[49] Tu, C.P.D., Reddy, C.C., 1985. On the multiplicity of rat liver glutathione S-transferases. J. Biol. Chem., 260:9961-9964.

[50] Warburg, O., Christian, W., 1941. Isolierung und kristallisation des gärungsferments enolase. Biochemische Zeitschrift, 310:384-421.

[51] Wendel, A., 1981. Enzymatic Basis of Detoxification. In: Jakoby, W.B. (Ed.), Glutathione. Academic Press, New York, 1:333-353.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE