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Expression of glyoxalase I and II in normal and breast cancer tissues

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Abstract

The present work aimed to study the activities of glyoxalase system enzymes, glyoxalase I (G I) and glyoxalase II (G II), as well as the expression of their genes in human breast carcinoma. Samples of tumoral tissue and normal counterparts were drawn from several patients during surgery. They served either for preparing extracts to be used in enzyme activity evaluations or for RNA extraction and subsequent northern blot analysis. A far higher activity level of G I and G II occurs in the tumor compared with pair-matched normal tissue, as shown by both spectrophotometrical assay and electrophoretic pattern. Such increased activities of G I and G II likely result from an enhanced enzyme synthesis as a consequence of increased expression of the respective genes in the tumoral tissue, as evidenced by northern blot. The present findings confirm a key-role of glyoxalase system to detoxify cytotoxic methylglyoxal and modulate S-D-lactoylglutathione levels in tumor cells. Moreover, they suggest a possible employment of GI inhibitors as anti-cancer drugs.

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References

  1. Carrington SJ, Douglas KT: The glyoxalase enigma. The biological consequences of a ubiquitous enzyme. IRCS Med Sci 14: 763-768, 1986

    Google Scholar 

  2. Sellin S, Aronsson AC, Eriksson LEG, Larsen K, Tibbelin G, Mannervik B: Properties and catalytic functions of glyoxalase I. In: Larsen K, Mannervik B (eds) Functions of Glutathione: Biochemical, Physiological, Toxicological and Clinical Aspects. Raven Press, New York, 1983, pp 187-197

    Google Scholar 

  3. Uotila L: Purification and characterization of S-2-hydroxyacyl-glutathione hydrolase (glyoxalase II) from human liver. Biochemistry 12: 3944-3951, 1973

    Google Scholar 

  4. Phillips SA, Thornalley PJ: The formation of methylglyoxal from triosephosphates. Investigation using a specific assay for methylglyoxal. Eur J Biochem 212: 101-105, 1993

    Google Scholar 

  5. Reichard GA, Skutches CL, Hoeldtke: Acetone metabolism in humans during diabetic ketoacidosis. Diabetes 35: 668-674, 1986

    Google Scholar 

  6. Lyles GA, Chambers J: The metabolism of aminoacetone to methylglyoxal by semicarbazide-sensitive amine oxidase in human umbilical artery. Biochem Pharmacol 43: 1409-1414, 1992

    Google Scholar 

  7. Thornalley PJ, Langborg A, Minhas HS: Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 344: 109-116

  8. Ranganathan S, Walsh ES, Godwin AK, Tew KD: Cloning and characterization of human colon glyoxalase I. J Biol Chem 268: 5661-5667, 1993

    Google Scholar 

  9. Ridderstrom M, Mannervik B: Molecular cloning and characterization of the thiolesterase glyoxalase II from Arabidopsis thaliana. Biochem J 322: 449-454, 1997

    Google Scholar 

  10. Kalia S, Pal S, Guha-Mukherjee S: Activation of glyoxalase I during the cell division cycle and its homology with aux in regulated genes. Plant Sci 132: 55-62, 1998

    Google Scholar 

  11. Zheng X-F, Ruderman JV: Functional analysis of the P box, a doma in in cyclin B required for the activation of cdc25. Cell 75: 155-164, 1993

    Google Scholar 

  12. Thornalley PJ: Glutathione-dependent detoxification of alphaoxoaldehydes by the glyoxalase system: involvement in disease mechanisms and anti-proliferative activity of glyoxalase I inhibitors. Chem Biol Interact 111-112: 137-151, 1998

    Google Scholar 

  13. Kalapos MP: Methylglyoxal in living organisms. Chemistry, biochemistry, toxicology and biological implications. Toxicol Lett 110: 145-175, 1999

    Google Scholar 

  14. Okado A, Kawasaki Y, Hasuike Y, Takahashi M, Teshima T, Fujii J, Taniguchi N: Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines. Biochem Biophys Res Commun 225: 219-224, 1996

    Google Scholar 

  15. Amicarelli F, Bucciarelli T, Poma A., Aimola P, Di Ilio C, Ragnelli AM, Miranda M: Adaptive response of human melanoma cells to methylglyoxal. Carcinogenesis 19: 519-523, 1998

    Google Scholar 

  16. Kalapos MP: On the promine-retine theory of cell division: now and then. Biochem Biophys Acta 1426: 1-16, 1999

    Google Scholar 

  17. Principato GB, Bodo M, Biagioni M, Rosi G, Liotti FS: Glyoxalase and glutathione reductase activity changes in chicken liver during embryo development and after hatching. Acta Embryol Morphol Exp 3: 173-179, 1982

    Google Scholar 

  18. Principato GB, Locci P, Rosi G, Talesa V, Giovannini E: Activity changes of glyoxalase I-II and glutathione reductase in regenerating rat liver. Biochem Intern 6: 249-255, 1983

    Google Scholar 

  19. Ranganathan S, Walsh ES, Tew KD: Glyoxalase I in detoxification: studies using a glyoxalase I transfectant cell line. Biochem J 309: 127-131, 1995

    Google Scholar 

  20. Jerzykowski T, Winter R, Matuszewski W, Piskorska D: A re-evaluation of studies on the distribution of glyoxalase in animal and tumor tissues. Int J Biochem 9: 853-860, 1978

    Google Scholar 

  21. Hooper NI, Tisdale MJ, Thornalley PJ: Glyoxalase activity during differentiation of human leukaemia cells in vitro. Leukaemia Res 11: 1141-1148, 1987

    Google Scholar 

  22. Hooper NI, Tisdale MJ, Thornalley PJ: Modification of the glyoxalase system in human HL60 promyelocytic leukaemics cells during differentiation to neutrophils in vitro. Biochim Biophys Acta 966: 362-369, 1988

    Google Scholar 

  23. Racker E: On the mechanism of action of glyoxalase. J Biol Chem 190: 685-696, 1951

    Google Scholar 

  24. Talesa V, Uotila L, Koivusalo M, Principato G, Giovannini E, Rosi G: Demonstration of glyoxalase II in rat liver mitochondria. Partial purification and occurrence in multiple forms. Biochim Biophys Acta 955: 103-110, 1988

    Google Scholar 

  25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein mesurement with the Folin phenol reagent. J Biol Chem 193: 265-275, 1951

    Google Scholar 

  26. McLellan AC, Thornalley PJ: Optimization of nonpolyacrylamide gel electrophoretic analysis of glyoxalase I phenotypes in clinical blood samples. Clin Chim Acta 204: 137-144, 1991

    Google Scholar 

  27. Uotila L: Glutathione thiol esterases of human red blood cells. Fractionation by gel electrophoresis and isoelectric focusing. Biochim Biophys Acta 580: 277-288, 1979

    Google Scholar 

  28. Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156-159, 1987

    Google Scholar 

  29. Sambrook J, Fritsch EF, Maniatis T: Molecular Cloning. A laboratory manual. Book 1. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1989, Chapter 7

    Google Scholar 

  30. Church GM, Gilbert W: Genomic sequencing. Proc Natl Acad Sci USA 81: 1991-1995, 1984

    Google Scholar 

  31. Ridderstrom M, Saccucci F, Hellman U, Bergman T, Principato G, Mannervik B: Molecular cloning, heterologous expression, and characterization of human glyoxalase II. J Biol Chem 271: 319-323, 1996

    Google Scholar 

  32. Davidson SD, Cherry JP, Choudhury MS, Tazaki H, Mallouh C, Konno S: Glyoxalase I activity in human prostate cancer: a potential marker and importance in chemoterapy. J Urol 161: 690-691, 1999

    Google Scholar 

  33. Di Ilio C, Angelucci S, Pennelli A, Zezza A, Tenaglia R, Sacchetta P: Glyoxalase activities in tumor and non-tumor human urogenital tissues. Cancer Lett 96: 189-193, 1995

    Google Scholar 

  34. Vander Jagt D: The glyoxalase system. In: Poulson D, Dolphin R, Avramovic O (eds) Glutathione: Chemical, Biochemical and Medical Aspects-Part A. Wiley, New York, 1989, pp 597-641

    Google Scholar 

  35. Thornalley JP, Della Bianca V, Bellavite P, Rossi F: S-Dlactoylglutathione in resting and activated human neutrophils. Biochem Biophys Res Commun 145: 769-774, 1987

    Google Scholar 

  36. Kalapos MP, Garzo' T, Antoni F, Mandl J: Accumulation of S-D-lactoylglutathione and transient decrease of glutathione level caused by methylglyoxal load in isolated hepatocytes. Biochim Biophys Acta 1135: 159-164, 1992

    Google Scholar 

  37. Gillespie E: Cell-free microtubule assembly: evidence for control by glyoxalase. Fed Proc 34: 541, 1975

    Google Scholar 

  38. Lo TWC, Thornalley PJ: Inhibition of proliferation of human leukaemia 60 cells by diethyl esters of glyoxalase inhibitors in vitro. Biochem Pharmacol 44: 2357-2363, 1992

    Google Scholar 

  39. Kavarana MJ, Kovaleva EG, Creighton DJ, Wollman MB, Eiseman JL: Mechanism-based competitive inhibitors of glyoxalase I: intracellular delivery, in vitro antitumor activities, and stabilities in human serum and mouse serum. J Med Chem 42: 221-228, 1999

    Google Scholar 

  40. Hamilton DS, Kavarana MJ, Sharkey EM, Eiseman JL, Creighton DJ: A new method for rapidly generating inhibitors of glyoxalase I inside tumor cells using S-(N-aryl-Nhydroxycarbamoyl) ethylsulfoxides. J Med Chem 42: 1823-1827, 1999

    Google Scholar 

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Rulli, A., Carli, L., Romani, R. et al. Expression of glyoxalase I and II in normal and breast cancer tissues. Breast Cancer Res Treat 66, 67–72 (2001). https://doi.org/10.1023/A:1010632919129

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