Skip to main content

Advertisement

SpringerLink
Log in

Selective expression of detoxifying glutathione transferases in mouse colon: effect of experimental colitis and the presence of bacteria

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Glutathione transferases (GSTs) play a central role in the cellular defense against harmful endogenous compounds and xenobiotics in mouse and man. The gastrointestinal channel is constantly exposed to bacteria, bacterial products, and xenobiotics. In the present study the distribution of alpha, mu, and pi class GSTs was examined immunohistologically in the colon of conventional and germ-free (GF) mice subjected to experimental colitis. The tissues samples were from conventional mice with and without colitis induced by dextran sulfate sodium (DSS); GF mice treated with DSS or carrageenan; and GF mice inoculated with normal mouse bacterial flora as well as with Lactobacillus GG. In conventional as well as in GF mice the mu and pi class GSTs showed reduced intestinal expression when colitis was induced. In contrast, the level of GSTs reacting with antibodies directed against the alpha class, in particular mGST A4-4, was elevated after induction of inflammation. Of special interest is mGST A4-4 because of its high catalytic activity with toxic products of lipid peroxidation. In the colon of conventionalized GF mice that were given mouse intestinal flora, the mGST A4-4 expression was increased with time for several weeks, but then showed a decrease to a normal level. Additionally, the inoculation of GF mice with Lactobacillus GG induced all the intestinal GSTs studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A–E
Fig. 2A–F

Similar content being viewed by others

References

  • Alder V, Yin Z, Fuchs SY, Benezra M, Rosario L, Tew KD, Pincus MR, Sardana M, Henderson CJ, Wolf CR, Davis RJ, Ronai Z (1999) Regulation of JNK signaling by GSTp. EMBO J 18:1321–1334

    Article  PubMed  Google Scholar 

  • Axelsson L-G (1996) Experimental animal models for the study of inflammatory bowel diseases and gastrointestinal anti-inflammatory drugs. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology 215, Uppsala, Sweden, pp 62 (ISBN 91-554-3781-4)

  • Axelsson L-G (1999) Xenobiotics, intestinal microflora and innate gastrointestinal immunity: what can clinical observations and experimental animal models tell us about environmentally related diseases. Microecol Ther 28:327–335

    CAS  Google Scholar 

  • Axelsson L-G, Midtvedt T (1997) Sulfation and Mw-optimized carrageenan induces colon inflammation in germfree mice. Gastroenterology 112:A925

    Google Scholar 

  • Axelsson L-G, Landström E, Goldschmidt TJ, Gronberg A, Bylund-Fellenius AC (1996a) Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice. Effects in CD4+-cell depleted, athymic and NK-cell depleted SCID mice. Inflamm Res 45:181–191

    CAS  PubMed  Google Scholar 

  • Axelsson L-G, Midtvedt T, Bylund-Fellenius A-C (1996b) The role of intestinal bacteria, bacterial translocation and endotoxin in dextran sodium sulfate-induced colitis in the mouse. Microb Ecol Health Dis 9:225–237

    Article  Google Scholar 

  • Axelsson L-G, Landström E, Bylund-Fellenius A-C (1998) Experimental colitis induced by dextran sulfate sodium in mice: beneficial effects of sulfasalazine and olsalazine. Aliment Pharmacol Ther 12:925–934

    Article  CAS  PubMed  Google Scholar 

  • Berhane K, Widersten M, Engström A, Kozarich JW, Mannervik B (1994) 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 U S A 91:1480–1484

    Google Scholar 

  • Board PG, Coggan M, Chelvanayagam G, Easteal S, Jermiin LS, Schulte GK, Danley DE, Hoth LR, Griffor MC, Kamath AV, Rosner MH, Chrunyk BA, Perregaux DE, Gabel CA, Geoghegan KF, Pandit J (2000) Identification, characterization, and crystal structure of the Omega class glutathione transferases. J Biol Chem 275:24798–24806

    Article  CAS  PubMed  Google Scholar 

  • Bruin WCC de, Wagenmans MJM, Board PG, Peters WHM (1999) Expression of glutathione S-transferase theta class isoenzymes in human colorectal and gastric cancers. Carcinogenesis 20:1453–1457

    Article  PubMed  Google Scholar 

  • Bruin WCC de, Wagenmans MJM, Peters WHM (2000) Expression of glutathione S-transferase alpha, P1-1 and T1-1 in the human gastrointestinal tract. Jpn J Cancer Res 9:310–316

    Google Scholar 

  • Bylund-Fellenius A-C, Landström E, Axelsson L-G, et al (1994) Experimental colitis induced by dextran sulfate in normal and germfree mice. Microb Ecol Health Dis 7:207–215

    Google Scholar 

  • Cheng JZ, Singhal SS, Saini M, Singhal J, Piper JT, Van Kuijk FJ, Zimniak P, Awasthi YC, Awasthi S (1999) Effects of mGST A4 transfection on 4-hydroxynonenal-mediated apoptosis and differentiation of K562 human erythroleukemia cells. Arch Biochem Biophys 372:29–36

    Article  CAS  PubMed  Google Scholar 

  • Cho SG, Lee YH, Park HS, Ryoo K, Kang KW, Park J, Eom SJ, Kim MJ, Cang TS, Choi SY, Shim J, Kim Y, Dong MS, Lee MJ, Kim SG, Ichijo H, Choi EJ (2001) Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J Biol Chem 26:12749–12755

    Article  Google Scholar 

  • Clapper ML, Adrian RH, Pfeiffer GR, Kido K, Everley L, Cooper HS, Murthy S (1999) Depletion of colonic detoxication enzyme activity in mice with dextran sulfate sodium-induced colitis. Aliment Pharmacol Ther 13:389–396

    Article  CAS  PubMed  Google Scholar 

  • Cooper HS, Murthy SNS, Shah RS, Sedergran DJ (1993) Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238–249

    CAS  PubMed  Google Scholar 

  • Cooper HS, Murthy S, Kido K, Yoshitake H, Flanigan A (2000) Dysplasia and cancer in the dextran sulfate sodium mouse colitis model. Relevance to colitis-associated neoplasia in the human: a study of the histopathology, B-catenin and p53 expression and the role of inflammation. Carcinogenesis 21:757–768

    Article  CAS  PubMed  Google Scholar 

  • Desmots F, Rissel M, Gilot D, Lagadic-Gossmann D, Morel F, Guguen-Guillouzo C, Guillouzo A, Loyer P (2002) 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 277:17892–17900

    Article  CAS  PubMed  Google Scholar 

  • Edalat M, Pettersson S, Persson MA, Mannervik B (2002) Probing biomolecular interactions of glutathione transferase M2-2 by using peptide phage display. Chembiochem 3:823–828

    Article  CAS  PubMed  Google Scholar 

  • Elson CO, Sartor RB, Tennyson GS, Riddell RH (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367

    CAS  PubMed  Google Scholar 

  • French N, Pettersson S (2000) Microbe-host interactions in the alimentary tract: the gateway to understanding inflammatory bowel disease. Gut 47:162–163

    Article  CAS  PubMed  Google Scholar 

  • Grisham MB (1993) Animal models of inflammatory bowel disease. Curr Opin Gastroenterol 9:524–533

    Google Scholar 

  • Gustafsson BE (1959) Lightweight stainless steel systems for rearing germfree animals. NY Acad Sci 78:17–28

    CAS  Google Scholar 

  • Hao XY, Castro VM, Bergh J, Sundström B, Mannervik B (1994) Isoenzyme-specific quantitative immunoassays for cytosolic glutathione transferases and measurement of the enzymes in blood plasma from cancer patients and in tumor cell lines. Biochim Biophys Acta 1225:223–230

    Article  CAS  PubMed  Google Scholar 

  • Hayes JD, McLellan LI (1999) Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res 1:273–300

    Google Scholar 

  • Hirono I, Sumi Y, Kuhara K, Miyakawa M (1981) Effect of degraded carrageenan on the intestine in germfree rats. Toxicol Lett 8:207–212

    Article  CAS  PubMed  Google Scholar 

  • Hooper LV, Gordon JI (2001) Commensal host-bacterial relationships in the gut. Science 292:1115–1118

    Article  CAS  PubMed  Google Scholar 

  • Hubatsch I, Ridderström M, Mannervik B (1998) Human glutathione transferase A4-4: an alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation. Biochem J 330:175–179

    CAS  PubMed  Google Scholar 

  • Ishioka T, Kuwabara N, Oohasi Y, Wakabayashi K (1987) Induction of colorectal tumors in rats by sulfated polysaccharides. CRC Crit Rev Toxicol 17:215–244

    CAS  Google Scholar 

  • Kimura J, Hayakari M, Kumano T, Nakano H, Satoh K, Tsuchida S (1998) Altered glutathione transferase levels in rat skin inflamed due to contact hypersensitivity: induction of the alpha-class subunit 1. Biochem J 335:605–610

    CAS  PubMed  Google Scholar 

  • Malin M, Suomalainen H, Saxelin M, Isolauri E (1996) Promotion of IgA immune response in patients with Crohn’s disease by oral bacteriotherapy with Lactobacillus GG. Ann Nutr Metab 40:137–145

    CAS  PubMed  Google Scholar 

  • Mannervik B (1985) The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol 57:357–417

    CAS  PubMed  Google Scholar 

  • Mannervik B, Danielson UH (1988) Glutathione transferases: structure and catalytic activity. CRC Crit Rev Biochem 23:263–337

    Google Scholar 

  • Mannervik B, Ålin P, Guthenberg C, Jensson H, Tahir MK, Warholm M, Jörnvall H (1985) Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A 82:7202–7206

    CAS  PubMed  Google Scholar 

  • Marteau PR, de Vrese M, Cellier CJ, Schrezenmeir J (2001) Protection from gastrointestinal diseases with the use of probiotics. Am J Clin Nutr 73:430S–436S

    CAS  PubMed  Google Scholar 

  • Mattey DL, Hassell AB, Plant M, Dawes PT, Ollier WR, Jones PW, Fryer AA, Alldersea JE, Strange RC (1999) Association of polymorphism in glutathione S-transferase loci with susceptibility and outcome in rheumatoid arthritis: comparison with the shared epitope. Ann Rheum Dis 58:164–168

    CAS  PubMed  Google Scholar 

  • Morgenstern R, DePierre JW, Jörnvall H (1985) Microsomal glutathione transferase: primary structure. J Biol Chem 260:13976–13983

    Google Scholar 

  • Nieto N, Torres MI, Fernández MI, Giron MD, Rios A, Suarez MD, Gil A (2000) Experimental ulcerative colitis impairs antioxidant defense system in rat intestine. Dig Dis Sci 45:1820–1827

    Article  CAS  PubMed  Google Scholar 

  • Oestreicher P, Nielsen ST, Rainsford KD (1992) Sulphasalazine fails to prevent development of mucosal ulceration and 5-lipoxygenase activity in guinea-pigs with chronic inflammatory bowel disease induced by combined bacterial immunization and oral carrageenin. J Pharm Pharmacol 44:528–531

    CAS  PubMed  Google Scholar 

  • Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R (1990) A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694–702

    CAS  PubMed  Google Scholar 

  • Ranganathan S, Tew KD (1991) Immunohistochemical localization of glutathione S-transferases alpha, mu, and pi in normal tissue and carcinomas from human colon. Carcinogenesis 12:2383–2387

    CAS  PubMed  Google Scholar 

  • Rollinson S, Levene AP, Mensah FK, Roddam PL, Allan JM, Diss TC, Roman E, Jack A, MacLennan K, Dixon MF, Morgan GJ (2003) Gastric marginal zone lymphoma is associated with polymorphisms in genes involved in inflammatory response and antioxidative capacity. Blood 102:1007–1011

    Article  CAS  PubMed  Google Scholar 

  • Schotte L, Steidler L, Vandekerckhove J, Remaut E (2000) Secretion of biologically active murine interleukin-10 by Lactococcus lactis. Enzyme Microb Technol 27:761–765

    Article  CAS  PubMed  Google Scholar 

  • Spiik A-K, Ridderstad A, Axelsson L-G, Midtvedt T, Björk L, Pettersson S (2002) P65 antisense oligonucleotides treatment inhibits lymphocyte infiltration and CD14 expression in dextran sulfate induced colitis in the mouse. Int J Colorectal Dis 17:223–232

    Article  PubMed  Google Scholar 

  • Steidler L, Hans W, Schotte L, Neirynck S, Obermeier F, Falk W, Fiers W, Remaut E (2000) Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289:1352–1355

    Article  CAS  PubMed  Google Scholar 

  • Uribe A, Alam M, Johansson O, Midtvedt T, Theodorsson E (1994) Microflora modulates endocrine cells in the gastrointestinal mucosa of the rat. Gastroenterology 107:1259–1269

    Google Scholar 

  • Vuilleumier S, Pagni M (2002) The elusive roles of bacterial glutathione S-transferases: new lessons from genomes. Appl Microb Biotech 58:138–146

    Article  CAS  Google Scholar 

  • Weiner ML (1991) Toxicological properties of carrageenan. Agents Actions 32:46–51

    CAS  PubMed  Google Scholar 

  • WHO Technical Reports Series (1984) Toxicological evaluation of certain food additives and food contaminants. Twenty-eighth report on the joint FAO/WHO expert committee on food additives, Geneva, pp 21–33

  • Willis CM, Britton LE, Reiche L, Wilkinson JD (2001) Reduced levels of glutathione S-transferases in patch test reactions to dithranol and sodium lauryl sulphate as demonstrated by quantitative immunocytochemistry: evidence for oxidative stress in acute irritant contact dermatitis. Eur J Dermatol 11:99–104

    CAS  PubMed  Google Scholar 

  • Yamada M, Ohkusa T, Okayasu I (1992) Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamster induced by dextran sulfate sodium. Gut 33:1521–1527

    CAS  PubMed  Google Scholar 

  • Yamada T, Sartor RB, Marshall S, Specian RD, Grisham MB (1993) Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats. Gastroenterology 104:759–771

    CAS  PubMed  Google Scholar 

  • Yin ZL, Dahlstrom JE, Le Couteur DG, Board PG (2001) Immunohistochemistry of omega class glutathione S-transferase in human tissues. J Histochem Cytochem 49:983–987

    CAS  PubMed  Google Scholar 

  • Zimniak P, Singhal SS, Srivastava SK, Awasthi S, Sharma R, Hayden JB, Awasthi YC (1994) Estimation of genomic complexity, heterologous expression, and enzymatic characterization of mouse glutathione S-transferase mGST A4-4 (GST 5.7). J Biol Chem 269:992–1000

    Google Scholar 

Download references

Acknowledgements

We thank Dr. Yogesh C. Awasthi, University of Texas Medical Branch, Galveston, TX, USA, for the antibody against mGST A4-4. We are also grateful to Ros-Mari Johansson, Sandra Stenberg, Eva Österlund, and Anna-Karin Persson for practical assistance in the experimental work. This investigation was supported by the Swedish Cancer Society.

Author information

Authors and Affiliations

  1. Microbiology and Tumor Biology Center (MTC), Gastrobiology Unit, Division of Molecular Pathology, Karolinska Institutet, Box 280, 171 77, Stockholm, Sweden

    Lars-Göran Axelsson

  2. Department of Biochemistry, Biomedical Center, Uppsala University, Box 576, 751 23, Uppsala, Sweden

    Maryam Edalat & Bengt Mannervik

Authors
  1. Maryam Edalat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bengt Mannervik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lars-Göran Axelsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars-Göran Axelsson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Edalat, M., Mannervik, B. & Axelsson, LG. Selective expression of detoxifying glutathione transferases in mouse colon: effect of experimental colitis and the presence of bacteria. Histochem Cell Biol 122, 151–159 (2004). https://doi.org/10.1007/s00418-004-0688-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-004-0688-7

Keywords

Search

Navigation