The importance of glutathione in human disease

Biomedicine and Pharmacotherapy

Volumn 57, Issue 3, 2003, Pages 145-155

  Townsend, Danyelle M ^a   Tew, Kenneth D ^a   Tapiero, Haim ^b  

^a FOX CHASE CANCER CENTER   (United States)

^b UNIV PARIS SUD   (France)

Author keywords

Glutathione (GSH); Glutathione transferases (GST); Human diseases; Reactive oxygen species (ROS)

Indexed keywords

DOXORUBICIN; GLUTAMATE CYSTEINE LIGASE; GLUTATHIONE; GLUTATHIONE TRANSFERASE; REACTIVE OXYGEN METABOLITE;

AGING; AMINO ACID SUBSTITUTION; CANCER; CANCER RISK; CLINICAL TRIAL; CYSTIC FIBROSIS; DRUG EFFECT; ENZYME DEFECT; GENE FUNCTION; GENE STRUCTURE; GENETIC ANALYSIS; GENETIC HETEROGENEITY; GENETIC POLYMORPHISM; GLUTATHIONE METABOLISM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIVER DISEASE; NONHUMAN; OXIDATION REDUCTION REACTION; PARKINSON DISEASE; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW;

EID: 0037733975     PISSN: 07533322     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0753-3322(03)00043-X     Document Type: Review

References (102)

1. Anderson M.E. Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact. 111-2:1998;1-14.
2. Mullineaux P., Creissen G.P. Glutathione reductase: regulation and role in oxidative stress. Oxidative stress and the molecular biology of antioxidant defenses. 1997;Cold Spring Harbor Laboratory Press.
3. Meister M.A.A. Glutathione. Annu Rev Biochem. 52:1983;711-760.
4. Sierra-Rivera E.S.M., Dasouki M., Krishnamani M.R., Phillips J.A., Freeman M.L. Assignment of the gene (GLCLC) that encodes the heavy subunit of y-glutamylcysteine synthetase to human chromosome 6. Cytogenet Cell Genet. 70:1995;278-279.
5. Sierra-Rivera E.D.M., Summar M.L., et al. Assignment of the human gene (GLCLR) that encodes the regulatory subunit of y-glutamylcysteine synthetase to chromosome 1p21. Cytogenet Cell Genet. 72:1996;252-254.
6. Bannai S., Christensen H.N., Vadgama J.V., Ellory J.C., Englesberg E., Guidotti G.G., et al. Amino acid transport systems. Nature. 311:1984;308.
7. Moinova H.R., Mulcahy R.T. An electrophilic responsive element (EpRE) regulates beta-naphthoflavone induction of the human gamma-glutamylcysteine synthetase regulatory subunit gene. Constitutive expression is mediated by an adjacent AP-1 site. J Biol Chem. 273:1998;14683-14689.
8. Wild A., Gipp J.J., Mulcahy T. Overlapping antioxidant response element and PMA response element sequences mediate basal and beta-naphthoflavone-induced expression of the human gamma-glutamylcysteine synthetase catalytic subunit gene. Biochem J. 332:(Pt 2):1998;373-381.
9. Rahman I.S.C., Antonicelli F., MacNee W. Characterisation of y-glutamylcysteine-heavy subunit gene promoter: critical role for AP-1. FEBS Lett. 427:1998;129-133.
10. Bella D.L., Hosokawa Y., Stipanuk M.H. Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo. Am J Physiol. 276:1999;E326-E335.
11. Gomi A.M.T., Ishikawa T., Kuo M.T. Posttranscriptional regulation of MRP/GS-X pump and y-glutamylcysteine synthetase expression by 1(4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea and by cycloheximide in human glioma cells. Biochem Biophys Res Commun. 239:1997;51-56.
12. Brigelius-Flohe R. Tissue-specific functions of individual glutathione peroxidases. Free Radical Biol M. 27:1999;951-965.
13. Downey J.S., Bingle C.D., Cottrell S., Ward N., Churchman D., Dobrota M., et al. The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis. Biochem Biophys Res Commun. 244:1998;463-467.
14. Banki K., Hutter E., Gonchoroff N.J., Perl A. Molecular ordering in HIV-induced apoptosis. Oxidative stress, activation of caspases, and cell survival are regulated by transaldolase. J Biol Chem. 273:1998;11944-11953.
15. Shisler J.L., Senkevich T.G., Berry M.J., Moss B. Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus. Science. 279:1998;102-105.
16. Okamoto K., Toyokuni S., Uchida K., Ogawa O., Takenewa J., Kakehi Y., et al. Formation of 8-hydroxy-2′-deoxyguanosine and 4-hydroxy-2-nonenal-modified proteins in human renal-cell carcinoma. Int J Cancer. 58:1994;825-829.
17. Chinery R., Beauchamp R.D., Shyr Y., Kirkland S.C., Coffey R.J., Morrow J.D. Antioxidants reduce cyclooxygenase-2 expression, prostaglandin production, and proliferation in colorectal cancer cells. Cancer Res. 58:1998;2323-2327.
18. Lee Y.J., Galoforo S.S., Berns C.M., Chen J.C., Davis B.H., Sim J.E., et al. Glucose deprivation-induced cytotoxicity and alterations in mitogen-activated protein kinase activation are mediated by oxidative stress in multidrug-resistant human breast carcinoma cells. J Biol Chem. 273:1998;5294-5299.
19. Kamata H., Hirata H. Redox regulation of cellular signalling. Cell Signal. 11:1999;1-14.
20. Roxas V.P., Smith R.K., Allen E.R., Allen R.D. Overexpression of glutathione S-transferase/glutathione peroxidase enhances the growth of transgenic tobacco seedlings during stress. Nat Biotechnol. 15:1997;988-991.
21. Lind C., Gerdes R., Schuppe-Koistinen I., Cotgreave I.A. Studies on the mechanism of oxidative modification of human glyceraldehyde-3 phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. Biochem Biophys Res Commun. 247:1998;481-486.
22. Klatt P., Pineda-Molina E., Garcia de Lacoba M., Padilla A., Martinez-Galisteo E., Barcena J.A., et al. Redox regulation of c-Jun DNA binding by reversible S-glutathiolation. FASEB J. 13:1999;1481-1490.
23. Itoh K., Wakabayashi N., Katoh Y., Ishii T., Igarashi K., Engel J.D., et al. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13:1999;76-86.
24. Alam J., Camhi S., Choi A.M.K. Identification of a second region upstream of the mouse heme oxygenase-1 gene that functions as a basal level and induce dependent transcriptional enhancer. J Biol Chem. 270:1995;11977-11984.
25. Ward N.E., Pierce D.S., Chung S.E., Gravitt K.R., O'Brian C.A. Irreversible inactivation of protein kinase C by glutathione. J Biol Chem. 273:1998;12558-12566.
26. Wilhelm D., Bender K., Knebeland A.P. The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including jun N-terminal protein kinases and p38 kinase by alkylating agents. Mol Cell Biol. 17:1997;4792-4800.
27. Rainwater R., Parks D., Anderson M.E., Tegtmeyer P., Mann K. Role of cysteine residues in regulation of p53 function. Mol Cell Biol. 15:1995;3892-3903.
28. Liu M., Pelling J.C., Ju J., Chu E., Brash D.E. Antioxidant action via p53-mediated apoptosis. Cancer Res. 58:1998;1723-1729.
29. Herzenberg L.A., DeRosa S.C., Dubs J.G., Roederer M., Anderson M.T., Ela S.W., et al. Glutathione deficiency is associated with impaired survival in HIV disease. Proc Natl Acad Sci USA. 94:1997;1967-1972.
30. Dong C., Yang D.D., Wysk M., Whitmarsh A.J., Davis R.J., Flavell R.A. Defective T-cell differentiation in the absence of JNK1. Science. 281:1998;2092-2095.
31. Powis G., Kirkpatrick D.L., Angulo M., Baker A. Thioredoxin redox control of cell growth and death and the effects of inhibitors. Chem Biol Interact. 111-112:1998;23-24.
32. Saitoh M., Nishitoh H., Fujii M., Takeda K., Tobiume K., Sawada Y., et al. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 17:1998;2596-2606.
33. Gotoh Y., Cooper J.A. Reactive oxygen species and dimerization-induced activation of apoptosis signal-regulating kinase 1 in tumor necrosis factor-alpha signal transduction. J Biol Chem. 273:1998;17477-17482.
34. Makino Y., Yoshikawa N., Okamoto K., Hirota K., Yodoi J., Makino I., et al. Direct Association with thioredoxin allows redox regulation of glucocorticoid receptor function. J Biol Chem. 274:1999;3182-3188.
35. Casagrande S., Bonetto V., Fratelli M., Gianazza E., Eberini I., Massignan T., et al. Glutathionylation of human thioredoxin: a possible crosstalk between the glutathione and thioredoxin systems. Proc Natl Acad Sci USA. 99:2002;9745-9749.
36. Shen H., Tsuchida S., Tamai K., Sato K. Identification of cysteine residues involved in disulfide formation in the inactivation of glutathione transferase P-form by hydrogen peroxide. Arch Biochem Biophys. 300:1993;137-141.
37. Walsh A.C., Rosen D.R., Lawrence D.A. Genetic mapping of GLCLC, the human gene encoding the catalytic subunit of y-glutamylcysteine synthetase, to chromosome band 6pl 12 and characterisation of a polymorphic trinucleotide repeat within its 5′-untranslated region. Cytogenet Cell Genet. 75:1996;114-116.
38. Shi Z.Z., Kala G., Kala S.V., Barrios R.J., Habib G.M., Lukin D.J., et al. Glutathione synthesis is essential for mouse development but not for cell growth in culture. Proc Natl Acad Sci USA. 97:2000;5101-5106.
39. Beutler E.G.T., Kondo T., Matsunaga A.T. The molecular basis of a case of y-glutamylcysteine synthetase deficiency. Blood. 94:1999;2890-2894.
40. Rozet J.M., Perrault I., et al. Structure and refinement of the physical mapping of the y-glutamylcysteine ligase regulatory subunit (GLCLR) gene to chromosome 1p22.1 within the critically deleted region of human malignant mesothelioma. Cytogenet Cell Genet. 82:1998;91-94.
41. Jakobsson P.J., Thoren S., Morgenstern R., Samuelsson B. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA. 96:1999;7220-7225.
42. Mannervik B. The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol. 57:1985;357-417.
43. Tew K.D. Glutathione-associated enzymes in anticancer drug resistance. Cancer Res. 54:1994;4313-4320.
44. McLellan L.I., Wolf C.R. Glutathione and glutathione-dependent enzymes in cancer drug resistance. Drug Resist Update. 2:1999;153-164.
45. Tang A.H., Tu C.P. Biochemical characterization of Drosophila glutathione S-transferases D1 and D21. J Biol Chem. 269:1994;27876-27884.
46. Ranson H., Prapanthadara L., Hemingway J. Cloning and characterization of two glutathione S-transferases from a DDT-resistant strain of Anopheles gambiae. Biochem J. 324:(Pt 1):1997;97-102.
47. Adler V., Yin Z., Fuchs S.Y., Benerza M., Rosario L., Tew K.D., et al. Regulation of JNK signaling by GSTp. EMBO J. 18:1999;1321-1334.
48. Yin Z., Ivanov V., Habelhah H., Tew K.D., Ronai Z. Glutathione S-transferase p elicits protection against hydrogen peroxide-induced cell death via coordinated regulation of stress kinases. Cancer Res (Adv. In Brief). 60:2000;4053-4057.
49. Cho S.G., Lee Y.H., Park H.S., Ryoo K., Kang K.W., Park J., et al. Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J Biol Chem. 276:2001;12749-12755.
50. Davis R.J. Signal transduction by the JNK group of MAP kinases. Cell. 103:2000;239-252.
51. Ono K., Han J. The p38 signal transduction pathway: activation and function. Cell Signal. 12:2000;1-13.
52. Smith G., Stanley L.A., Sim E., Strange R.C., Wolf C.R. Metabolic polymorphisms and cancer susceptibility. Cancer Surv. 25:1995;27-65.
53. Strange R.C., Jones P.W., Fryer A.A. Glutathione S-transferase: genetics and role in toxicology. Toxicol Lett. 112-3:2000;357-363.
54. Smith C.M., Kelsey K.T., Wiencke J.K., Leyden K., Levin S., Christiani D.C. Inherited glutathione-S-transferase deficiency is a risk factor for pulmonary asbestosis. Cancer Epidemiol Biomarkers Prev. 3:1994;471-477.
55. Nelson H.H., Wiencke J.K., Christiani D.C., Cheng T.J., Zuo Z.F., Schwartz B.S., et al. Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta. Carcinogenesis. 16:1995;1243-1245.
56. Strange R.C., Fryer A.A. The glutathione S-transferases: influence of polymorphism on cancer susceptibility. IARC Sci Publ. 1999;231-249. [Chapter 19].
57. Chenevix-Trench G., Young J., Coggan M., Board P. Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset. Carcinogenesis. 16:1995;1655-1657.
58. Pearson W.R., Vorachek W.R., Xu S.J., Berger R., Hart I., Vannais D., et al. Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13. Am J Hum Genet. 53:1993;220-233.
59. DeJong J.L., Mohandas T., Tu C.P. The human Hb (mu) class glutathione S-transferases are encoded by a dispersed gene family. Biochem Biophys Res Commun. 180:1991;15-22.
60. Baez S., Segura-Aguilar J., Widersten M., Johansson A.S., Mannervik B. Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochem J. 324:(Pt 1):1997;25-28.
61. Cowell I.G., Dixon K.H., Pemble S.E., Ketterer B., Taylor J.B. The structure of the human glutathione S-transferase pi gene. Biochem J. 255:1988;79-83.
62. Lo H.W., Ali-Osman F. Structure of the human allelic glutathione S-transferase-pi gene variant, hGSTP1 C, cloned from a glioblastoma multiforme cell line. Chem Biol Interact. 111-2:1998;91-102.
63. Goto S., Iida T., Cho S., Oka M., Kohno S., Kondo T. Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells. Free Radical Res. 31:1999;549-558.
64. Watson M.A., Stewart R.K., Smith G.B., Massey T.E., Bell D.A. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 19:1998;275-280.
65. Stoehlmacher J., Park D.J., Zhang W., Groshen S., Tsao-Wei D.D., Yu M.C., et al. Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst. 94:2002;936-942.
66. Ristoff E., Larsson A. Patients with genetic defects in the gamma-glutamyl cycle. Chem Biol Interact. 111-2:1998;113-121.
67. Shi Z.Z., Habib G.M., Rhead W.J., Gahl W.A., He X., Sazer S., et al. Mutations in the glutathione synthetase gene cause 5-oxoprolinuria. Nat Genet. 14:1996;361-365.
68. Dringen R.G.J., Hirlinger J. Glutathione metabolism in the brain. Eur J Biochem. 267:2000;4912-4916.
69. Halliwell B., Gutteridge J.M. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts. Arch Biochem Biophys. 246:1986;501-514.
70. Youdim M.B. Understanding Parkinson's disease. Sci Am. 276:1997;52-59.
71. Forno L.S. Neuropathology of Parkinson's disease. J Neuropathol Exp Neurol. 55:1996;259-272.
72. Sofic E.L.K., Jellinger K., Riederer P. Reduced and oxidized glutathione in the substantial nigra of patients with Parkinson's disease. Neurosci Lett. 142:1992;128-130.
73. Adams J.D. Jr, Klaidman L.K. Parkinson's disease - redox mechanisms. Curr Med Chem. 8:2001;809-814.
74. Andersen J.K., Hom D.G., Lee F.Y., Harnish P., Hamill R.W., McNeil T.H. Effect of buthionine sulfoximine, a synthesis inhibitor of the antioxidant glutathione, on the murine nigrostriatal neurons. J Neurochem. 67:1996;2164-2171.
75. Sechi G.D.M., Bua G., Satta W.M., Deiana G.A., Pes G.M., Rosati G. Reduced intravenous glutathione in the treatment of early Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry. 20:1996;1159-1170.
76. Buhl R., Jaffe H.A., Holroyd K.J., Wells F.B., Mastrangeli A., Saltini C., et al. Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet. 2:1989;1294-1298.
77. Staal F., Roederer M., Herzenberg L.A., Herzenberg L.A. Intracellular thiols regulate activation of nuclear factor kB and transcription of human immunodeficiency virus. Proc Natl Acad Sci USA. 87:1990;9943-9947.
78. Duh E., Maury W.J., Folks T.M., Fauci A.S., Rabson A.B. Tumor necrosis factor alpha activates human immunodeficiency virus type 1 through induction of nuclear factor binding to the NF-kappa B sites in the long terminal repeat. Proc Natl Acad Sci USA. 86:1989;5674-5678.
79. Suthanthiran M., Anderson M.E., Sharma V.K., Meister A. Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc Natl Acad Sci USA. 87:1990;3343-3347.
80. Gil L., Martinez G., Gonzalez I., Tarinas A., Alvarez A., Giuliani A., et al. Contribution to characterization of oxidative stress in HIV/AIDS patients. Pharmacol Res. 47:2003;217-224.
81. Nakamura H.M.H., Yodoi J. Redox imbalance and its control in HIV infection. Antioxid Redox Signal. 4:2002;455-464.
82. DeRosa S.C., Zaretsky M.D., Dubs J.G., Roederer M., Anderson M., Green A., et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest. 30:(10):2000;915-929.
83. Micke P.B.K., Schlaak J.F., Buhl R. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest. 31:2001;171-178.
84. Fernandez-Checa J.C., Colell A., Garcia-Ruiz C. S-adenosyl-L-methionine and mitochondrial reduced glutathione depletion in alcoholic liver disease. Alcohol. 27:(3):2002;179-183.
85. Fernandez-Checa J.C., Kaplowitz N., Garcia-Ruiz C., Colell A. Mitochondrial glutathione: importance and transport. Semin Liver Dis. 18:(4):1998;389-401.
86. Barbaro G., DiLorenzo G., Soldini M., Parrotto S., Bellomo G., Belloni G., et al. Hepatic glutathione deficiency in chronic hepatitis C: quantitative evaluation in patients who are HIV positive and HIV negative and correlations with plasmatic and lymphocytic concentrations and with the activity of the liver disease. Am J Gastroenterol. 91:(12):1996;2569-2573.
87. Hudson V. Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation. Free Radical Biol M. 30:2001;1440-1461.
88. Roum J.H., Buhl R., McElvaney N.G., Borok Z., Crystal R.G. Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol. 75:1993;2419-2424.
89. Brown R.K., ScBurney A., Lunec J., Kelly F.J. Oxidative damage to DNA in patients with cystic fibrosis. Free Radical Biol M. 234:1995;137-146.
90. Brown R.K., Wyatt H., Price J.F., Kelly F.J. Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress. Eur Respir J. 9:1996;334-339.
91. Hull J., Thomson A.H. Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis. Thorax. 53:1998;1018-1021.
92. Buhl R., Vogelmeier C., Critenden M., Hubbard R.C., Hoyt R.F. Jr, Wilson E.M., et al. Augmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol. Proc Natl Acad Sci USA. 87:1990;4063-4067.
93. Roum J.H., Borok Z., McElvaney N.G., Grimes G.J., Bokser A.D., Buhl R., et al. Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis. J Appl Physiol. 87:1999;438-443.
94. Flint D.H., Tuminello J.F., Emptage M.H. The inactivation of Fe-S cluster containing hydro-lyases by superoxide. J Biol Chem. 268:1993;22369-22376.
95. Gardner P.R., Fridovich I. Superoxide sensitivity of the Escherichia coli aconitase. J Biol Chem. 266:1991;19328-19333.
96. Mallis R.J., Hamann M.J., Zhao W., Zhang T., Hendrich S., Thomas J.A. Irreversible thiol oxidation in carbonic anhydrase III: protection by S-glutathiolation and detection in aging rats. Biol Chem. 383:2002;649-662.
97. Koster J.F., Sluiter W. Is increased tissue ferritin a risk factor for atherosclerosis and ischaemic heart disease? Br Heart. 73:1995;208-209.
98. Toba G., Aigaki T. Disruption of the microsomal glutathione S-transferase-like gene reduces life span of Drosophila melanogaster. Gene. 8:2000;179-187.
99. Jones D.P., Mody V.C. Jr, Carlson J.L., Lynn M.J., Sternberg P. Jr. Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses. Free Radical Biol M. 33:2002;1290-1300.
100. Liu R.M. Down-regulation of gamma-glutamylcysteine synthetase regulatory subunit gene expression in rat brain tissue during aging. J Neurosci Res. 68:2002;344-351.
101. Knight J.A. The biochemistry of aging. Adv Clin Chem. 35:2000;1-62.
102. Murata Y., Amao M., Yoneda J., Hamuro J. Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging. Mol Immunol. 38:2002;747-757.