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Gama-glutamil transferazın oksidatif stres ve kardiyovasküler hastalıklarla ilişkisi

Year 2013, Volume: 35 Issue: 2, 291 - 301, 27.06.2013

Azize Şener Özge Çevik

Abstract

Özet

Gama-glutamil transferaz’ın (GGT) öncelikli rolü, hücre içi indirgenmiş glutatyon (GSH) sentezi için gerekli olan öncül amino asitleri, özellikle de sisteini sağlamak için hücre dışı GSH’ın yıkımıdır. Böylece enzim, antioksidan etki gösterir. Ancak, GGT tarafından ekstrasellüler GSH’ın katabolizması, ortamda geçiş metalleri varlığında reaktif oksijen türlerinin oluşumuna da neden olabilmektedir. Son epidemiyolojik çalışmalar serum GGT aktivitesi artışının (normal referans değerleri içinde) temelinde ateroskleroz olan kardiyovasküler hastalıklar için bir öngörücü olabileceğini göstermektedir. Bu derlemede GGT ile oksidatif stres arasındaki ilişkiye ve GGT’nin kardiyovasküler hastalıkların klinik değerlendirilmesinde ve patogenezinde önemi ile ilgili son bilgilere yer verilmiştir.

Anahtar sözcükler: Gama-glutamil transferaz; glutatyon, oksidatif stress, kardiyovasküler hastalıklar

 

Abstract

The primary role of the gamma-glutamyltransferase (GGT) is to break down the extracellular glutathione (GSH) in order to provide precursor amino acids especially cysteine, required for the intracellular GSH synthesis. Thus, the enzyme shows an antioxidant effect. However, it may cause reactive oxygen species generation in the presence of transition metals during the metabolism of GGT-catalysed extracellular GSH. Recent epidemiological researches have shown that elevated serum GGT activity, within its reference level range, is a marker of cardiovascular diseases, which brought on by atherosclerosis. In this review, recent knowledge on the association between GGT and oxidative stress as well as the importance of GGT activity in the pathogenesis and clinical evaluation of Cardiovascular Diseases has been discussed.

Keywords: Gamma-Glutamyltransferase, glutathione, oxidative stress, cardiovascular diseases

Keywords

Gamma-Glutamyltransferase glutathione oxidative stress cardiovascular diseases

References

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Gama-Glutamil Transferazın Oksidatif Stres ve Kardiyovasküler Hastalıklarla İlişkisi

Year 2013, Volume: 35 Issue: 2, 291 - 301, 27.06.2013

Azize Şener Özge Çevik

Abstract

Gama-glutamil transferaz’ın (GGT) öncelikli rolü, hücre içi indirgenmiş glutatyon (GSH) sentezi için gerekli olan  öncül amino asitleri, özellikle de sisteini sağlamak için hücre dışı GSH’ın yıkımıdır. Böylece enzim, antioksidan etki gösterir. Ancak, GGT tarafından ekstraselüler GSH’ın katabolizması, ortamda geçiş metalleri varlığında reaktif oksijen türlerinin oluşumuna da neden olabilmektedir. Son epidemiyolojik çalışmalar serum GGT aktivitesi artışının (normal referans değerleri içinde) temelinde ateroskleroz olan kardiyovasküler hastalıklar için bir öngörücü olabileceğini göstermektedir. Bu derlemede GGT ile oksidatif stres arasındaki ilişkiye ve GGT’nin kardiyovasküler hastalıkların klinik değerlendirilmesinde ve patogenezinde önemi ile ilgili son bilgilere yer verilmiştir.

 

 

 

Keywords

Gama-glutamil transferaz; glutatyon oksidatif stress kardiyovasküler hastalıklar

References

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  • Storozhenko S, Belles-Boix E, Babiychuk E, Hérouart D, Davey MW, Slooten L, Van Montagu M, Inzé D, Kushnir S. Gamma-glutamyl transpeptidase in transgenic tobacco plants. Cellular localization, processing, and biochemical properties. Plant Physiol 2002; 128: 1109-19.
  • Okada T, Suzuki H, Wada K, Kumagai H, Fukuyama K. Crystal structures of gamma-glutamyltranspeptidase from Escherichia coli, a key enzyme in glutathione metabolism, and its reaction intermediate. Proc Natl Acad Sci USA 2006; 103: 6471-76.
  • Şener A. Gamma-glutamiltransferaz. Turk J Bioch 1997; 23: 27-33.
  • Grisk O, Küster U, Ansorge S. The activity of gamma-glutamyl transpeptidase (gamma-GT) in populations of mononuclear cells from human peripheral blood. Biol Chem Hoppe-Seyler 1993; 374: 287-90.
  • Tager M, Ittenson A, Franke A, Frey A, Gassen HG, Ansorge S. GammaGlutamyl transpeptidase-cellular expression in populations of normal human mononuclear cells and patients suffering from leukemias. Ann Hematol 1995; 70: 237Şener A, Yardımcı T. Lectin affinity chromatography and electrophoretic properties of human platelet gamma-glutamyl transferase. Platelets 2000; 11: 325Şener A, Yardımcı T. Activity determination, kinetic analyses and isoenzyme identification of gamma glutamyltransferase in human neutrophils. J Biochem Mol Biol 2005; 38: 343-9.
  • Hanigan MH. Gamma-glutamyl transpeptidase, a glutathionase: Its expression and function in carcinogenesis. Chem Biol Interact 1998; 111-112: 333-42.
  • Rajpert-De Meyts E, Heisterkamp N, Groffen J. Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase. Proc Natl Acad Sci USA 1988; 85: 8840Whitfield JB. Gamma glutamyl transferase. Crit Rev Clin Lab Sci 2001; 38: 26335
  • Ikeda Y, Fujii J, Taniguchi N, Meister A. Expression of an active glycosylated human gamma-glutamyl transpeptidase mutant that lacks a membrane anchor domain. Proc Natl Acad Sci USA 1995; 92: 126-30.
  • Irvine DS. Glutathione as a treatment for male infertility. Rev Reprod 1996; 1: 612
  • Meister, A. Metabolism and transport of glutathione and other γ-glutamyl compouds. In: A. Larsson. Function of Glutathione: Biochemical, Physiological, Toxicological, and Clinical Aspects. 1st ed. New York: Raven Press; 1983: 1-22. Aksoy Y. The role of glutathione in antioxidant mechanism. T Klin J Med Sci 2002; 22: 442-8.
  • Forman HJ, Zhang H, Rinna A. Glutathione: Overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009; 30: 1-12.
  • Estrela JM, Ortega A, Obrador E. Glutathione in cancer biology and therapy. Crit Rev Clin Lab Sci 2006; 43: 143-81.
  • Orlowski M, Meister A. The gamma-glutamyl cycle: a possible transport system for amino acids. Proc Natl Acad Sci USA 1970; 67: 1248-55.
  • Griffith OW, Bridges RJ, Meister A. Transport of gamma-glutamyl amino acids: role of glutathione and gamma-glutamyl transpeptidase. Proc Natl Acad Sci USA 1979; 76: 6319-22.
  • Hanigan MH, Ricketts WA. Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. Biochemistry 1993; 32: 6302
  • Emdin M, Passino C, Franzini M, Paolicchi A, Pompella A. Gammaglutamyltransferase and pathogenesis of cardiovascular diseases. Future Cardiol 2007; 3: 263-70.
  • Abraham NZ, Carty RP, DuFour DR, Pincus MR. Cinical enzymology. In: McPherson MR, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. New York: Saunders; 2007: 245-62.
  • Parihar A, Parihar MS, Milner S, Bhat S. Oxidative stress and anti-oxidative mobilization in burn injury. Burns 2008; 34: 6-17.
  • Suzuki YJ, Forman HJ, Sevanian A. Oxidants as stimulators of signal transduction. Free Radic Biol Med 1996; 22: 269-85.
  • Moldovan L, Moldovan NI. Oxygen free radicals and redox biology of organelles. Histochem Cell Biol 2004; 122: 395-412. del Bello B, Paolicchi A, Comporti M, Pompella A, Maellaro E. Hydrogen peroxide produced during gamma-glutamyl transpeptidase activity is involved in prevention of apoptosis and maintainance of proliferation in U937 cells. FASEB J 1999; 13: 69-79.
  • Paolicchi A, Dominici S, Pieri L, Maellaro E, Pompella A. Glutathione catabolism as a signaling mechanism. Biochem Pharmacol 2002; 64: 1027-35.
  • Lu SC. Regulation of hepatic glutathione synthesis: Current concepts and controversies. FASEB J 1999; 13: 1169-83.
  • Rathbun WB, Killen CE, Holleschau AM, Nagasawa HT. Maintenance of hepatic glutathione homeostasis and prevention of acetaminophen-induced cataract in mice by L-cysteine prodrugs. Biochem Pharmacol 1996; 51: 1111-6.
  • Jones DP, Carlson JL, Mody VC, Cai J, Lynn MJ, Sternberg P. Redox state of glutathione in human plasma. Free Radic Biol Med 2000; 28: 625-35.
  • Stark AA. Oxidative metabolism of glutathione by gamma-glutamyl transpeptidase and peroxisome proliferation: the relevance to hepatocarcinogenesis. A hypothesis. Mutagenesis 1991; 6: 241-5.
  • Aberkane H, Stoltz JF, Galteau MM, Wellman M. Erythrocytes as targets for gamma-glutamyltranspeptidase initiated pro-oxidant reaction. Eur J Haematol 2002; 68: 262-71.
  • Pompella A, Corti A, Paolicchi A, Giommarelli C, Zunino F. Gammaglutamyltransferase, redox regulation and cancer drug resistance. Curr Opin Pharmacol 2007; 7: 360-6.
  • Giustarini D, Campoccia G, Fanetti G, Rossi R, Giannerini F, Lusini L, Di Simplicio P. Minor thiols cysteine and cysteinylglycine regulate the competition between glutathione and protein SH groups in human platelets subjected to oxidative stress. Arch Biochem Biophys 2000; 380: 1-10.
  • Spear N, Aust SD. Thiol-mediated NTA-Fe(III) reduction and lipid peroxidation. Arch Biochem Biophys 1994; 312: 198-202.
  • Dominici S, Paolicchi A, Corti A, Maellaro E, Pompella A. Prooxidant reactions promoted by soluble and cell-bound gamma-glutamyltransferase activity. Methods Enzymol 2005; 401: 484-501.
  • Essex DW. The role of thiols and disulfides in platelet function. Antioxid Redox Signal 2004; 6: 736-46.
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There are 80 citations in total.

Details

Primary Language English
Journal Section Reviews
Authors

Azize Şener

Özge Çevik

Publication Date June 27, 2013
Published in Issue Year 2013Volume: 35 Issue: 2

Cite

AMA Şener A, Çevik Ö. Gama-glutamil transferazın oksidatif stres ve kardiyovasküler hastalıklarla ilişkisi. CMJ. June 2013;35(2):291-301.