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The Importance Of Glutathione In Human Disease.

D. Townsend, K. Tew, H. Tapiero
Published 2003 · Biology, Medicine

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Reduced glutathione (GSH) is the most prevalent non-protein thiol in animal cells. Its de novo and salvage synthesis serves to maintain a reduced cellular environment and the tripeptide is a co-factor for many cytoplasmic enzymes and may also act as an important post-translational modification in a number of cellular proteins. The cysteine thiol acts as a nucleophile in reactions with both exogenous and endogenous electrophilic species. As a consequence, reactive oxygen species (ROS) are frequently targeted by GSH in both spontaneous and catalytic reactions. Since ROS have defined roles in cell signaling events as well as in human disease pathologies, an imbalance in expression of GSH and associated enzymes has been implicated in a variety of circumstances. Cause and effect links between GSH metabolism and diseases such as cancer, neurodegenerative diseases, cystic fibrosis (CF), HIV, and aging have been shown. Polymorphic expression of enzymes involved in GSH homeostasis influences susceptibility and progression of these conditions. This review provides an overview of the biological importance of GSH at the level of the cell and organism.
This paper references
10.1016/S0898-6568(99)00071-6
The p38 signal transduction pathway: activation and function.
K. Ono (2000)
10.1515/BC.2002.067
Irreversible Thiol Oxidation in Carbonic Anhydrase III: Protection by S-Glutathiolation and Detection in Aging Rats
R. J. Mallis (2002)
10.1093/CARCIN/16.7.1655
Glutathione S-transferase M1 and T1 polymorphisms: susceptibility to colon cancer and age of onset.
G. Chenevix-Trench (1995)
Antioxidants reduce cyclooxygenase-2 expression, prostaglandin production, and proliferation in colorectal cancer cells.
R. Chinery (1998)
10.1046/j.1365-2362.2000.00736.x
N‐acetylcysteine replenishes glutathione in HIV infection
S. D. De Rosa (2000)
10.1093/CARCIN/16.5.1243
Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta.
H. Nelson (1995)
10.1159/000134447
Genetic mapping of GLCLC, the human gene encoding the catalytic subunit of gamma-glutamyl-cysteine synthetase, to chromosome band 6p12 and characterization of a polymorphic trinucleotide repeat within its 5' untranslated region.
A. Walsh (1996)
10.1074/JBC.273.19.11944
Molecular Ordering in HIV-induced Apoptosis
K. Bánki (1998)
10.1073/PNAS.87.9.3343
Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.
M. Suthanthiran (1990)
10.1136/hrt.73.3.208
Is increased tissue ferritin a risk factor for atherosclerosis and ischaemic heart disease?
J. Koster (1995)
10.1016/S0009-2797(97)00153-1
Structure of the human allelic glutathione S-transferase-pi gene variant, hGSTP1 C, cloned from a glioblastoma multiforme cell line.
H. Lo (1998)
10.1016/0378-1119(80)90036-0
Construction of a SalI/PstI restriction map of spinach chloroplast DNA using low-gelling-temperature-agarose electrophoresis.
R. Herrmann (1980)
Identification of class-mu glutathione transferase genes GSTM1-GSTM5 on human chromosome 1p13.
W. Pearson (1993)
10.1093/CARCIN/19.2.275
Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution.
M. Watson (1998)
10.1016/S1043-6618(02)00320-1
Contribution to characterization of oxidative stress in HIV/AIDS patients.
Lizette Gil (2003)
10.1006/BBRC.1998.8695
Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin.
C. Lind (1998)
10.1038/NBT1097-988
Overexpression of glutathione S-transferase/glutathioneperoxidase enhances the growth of transgenic tobacco seedlings during stress
V. P. Roxas (1997)
10.1016/S0009-2797(97)00146-4
Glutathione: an overview of biosynthesis and modulation.
M. E. Anderson (1998)
10.1080/10715769900301121
Overexpression of glutathione S-transferase pi enhances the adduct formation of cisplatin with glutathione in human cancer cells.
S. Goto (1999)
10.1073/PNAS.94.5.1967
Glutathione deficiency is associated with impaired survival in HIV disease.
L. Herzenberg (1997)
10.1016/S0161-5890(01)00111-0
Intracellular thiol redox status of macrophages directs the Th1 skewing in thioredoxin transgenic mice during aging.
Y. Murata (2002)
10.1016/s0021-9258(18)55001-8
Superoxide sensitivity of the Escherichia coli aconitase.
P. R. Gardner (1991)
10.1006/BBRC.1998.8296
The LEC rat possesses reduced hepatic selenium, contributing to the severity of spontaneous hepatitis and sensitivity to carcinogenesis.
J. S. Downey (1998)
10.1055/S-2007-1007172
Mitochondrial glutathione: importance and transport.
J. Fernández-Checa (1998)
10.1046/J.1432-1327.2000.01597.X
Glutathione metabolism in brain
R. Dringen (2000)
10.1074/jbc.273.20.12558
Irreversible Inactivation of Protein Kinase C by Glutathione*
N. Ward (1998)
10.1054/DRUP.1999.0083
Glutathione and glutathione-dependent enzymes in cancer drug resistance.
L. McLellan (1999)
10.1016/S0741-8329(02)00229-X
S-Adenosyl-L-methionine and mitochondrial reduced glutathione depletion in alcoholic liver disease.
J. Fernández-Checa (2002)
10.2174/0929867013372995
Parkinson's disease--redox mechanisms.
J. D. Adams (2001)
10.1016/S0891-5849(02)01040-7
Redox analysis of human plasma allows separation of pro-oxidant events of aging from decline in antioxidant defenses.
D. Jones (2002)
10.1128/MCB.17.8.4792
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.
D. Wilhelm (1997)
10.1016/S0140-6736(89)91909-0
SYSTEMIC GLUTATHIONE DEFICIENCY IN SYMPTOM-FREE HIV-SEROPOSITIVE INDIVIDUALS
R. Buhl (1989)
10.1016/S0009-2797(97)00155-5
Patients with genetic defects in the ?-glutamyl cycle 1 The Conference on Glutathione and Glutathion
E. Ristoff (1998)
10.1152/JAPPL.1993.75.6.2419
Systemic deficiency of glutathione in cystic fibrosis.
J. H. Roum (1993)
Antioxidant action via p53-mediated apoptosis.
M. Liu (1998)
10.1016/0891-5849(94)00172-G
Oxidative damage to DNA in patients with cystic fibrosis.
R. Brown (1995)
10.1126/SCIENCE.282.5396.2092
Defective T cell differentiation in the absence of Jnk1.
C. Dong (1998)
10.1101/0.667-713
Glutathione Reductase: Regulation and Role in Oxidative Stress
P. Mullineaux (1997)
10.1126/SCIENCE.279.5347.102
Ultraviolet-induced cell death blocked by a selenoprotein from a human dermatotropic poxvirus.
J. Shisler (1998)
10.1016/S0898-6568(98)00037-0
Redox regulation of cellular signalling.
H. Kamata (1999)
10.1002/jnr.10217
Down‐regulation of γ‐glutamylcysteine synthetase regulatory subunit gene expression in rat brain tissue during aging
R. Liu (2002)
10.7916/D8571B9J
Glutathione S-transferase p elicits protection against H2O2-induced cell death via coordinated regulation of stress kinases.
Z. Yin (2000)
10.1006/BBRC.1997.7423
Posttranscriptional Regulation ofMRP/GS-XPump and γ-Glutamylcysteine Synthetase Expression by 1-(4-Amino-2-methyl-5-pyrimidinyl) methyl-3- (2-chloroethyl)-3-nitrosourea and by Cycloheximide in Human Glioma Cells
A. Gomi (1997)
10.1159/000134051
Assignment of the gene (GLCLC) that encodes the heavy subunit of gamma-glutamylcysteine synthetase to human chromosome 6.
E. Sierra-Rivera (1995)
10.1016/s0021-9258(18)41538-4
The inactivation of Fe-S cluster containing hydro-lyases by superoxide.
D. Flint (1993)
10.1016/S0378-4274(99)00230-1
Glutathione S-transferase: genetics and role in toxicology.
R. Strange (2000)
10.1089/15230860260196245
Redox imbalance and its control in HIV infection.
H. Nakamura (2002)
10.1073/PNAS.87.24.9943
Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus.
F. Staal (1990)
Oxidative stress and the molecular biology of antioxidant defenses.
J. G. Scandalios (1997)
Inherited glutathione-S-transferase deficiency is a risk factor for pulmonary asbestosis.
C. Smith (1994)
10.1016/0304-3940(92)90355-B
Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease
E. Sofić (1992)
10.1093/emboj/17.9.2596
Mammalian thioredoxin is a direct inhibitor of apoptosis signal‐regulating kinase (ASK) 1
M. Saitoh (1998)
10.1007/springerreference_175313
Metabolic polymorphisms and cancer susceptibility.
G. Smith (1995)
10.1042/BJ3240097
Cloning and characterization of two glutathione S-transferases from a DDT-resistant strain of Anopheles gambiae.
H. Ranson (1997)
10.1016/S0092-8674(00)00116-1
Signal Transduction by the JNK Group of MAP Kinases
R. Davis (2000)
10.1042/BJ3240025
Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes.
S. Baez (1997)
10.1016/S0378-1119(00)00246-8
Disruption of the microsomal glutathione S-transferase-like gene reduces life span of Drosophila melanogaster.
G. Toba (2000)
10.1042/BJ3320373
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.
A. Wild (1998)
10.1074/JBC.273.9.5294
Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells*
Y. J. Lee (1998)
10.1016/0003-9861(86)90305-X
Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts.
B. Halliwell (1986)
10.1016/S0891-5849(99)00173-2
Tissue-specific functions of individual glutathione peroxidases.
R. Brigelius-Flohé (1999)
10.1006/ABBI.1993.1019
Identification of cysteine residues involved in disulfide formation in the inactivation of glutathione transferase P-form by hydrogen peroxide.
H. Shen (1993)
10.1038/NG1196-361
Mutations in the glutathione synthetase gene cause 5–oxoprolinuria
Z. Shi (1996)
10.1016/S0065-2423(01)35014-X
The biochemistry of aging.
J. A. Knight (2000)
10.1038/311308B0
Amino acid transport systems
Shiro Bannai (1984)
10.1182/BLOOD.V94.8.2890.420K16_2890_2894
The Molecular Basis of a Case of γ-Glutamylcysteine Synthetase Deficiency
E. Beutler (1999)
10.1046/j.1365-2362.2001.00781.x
Oral supplementation with whey proteins increases plasma glutathione levels of HIV‐infected patients
P. Micke (2001)
10.1038/SCIENTIFICAMERICAN0197-52
Understanding Parkinson's disease.
M. B. Youdim (1997)
10.1016/S0006-291X(05)81248-3
The human Hb (mu) class glutathione S-transferases are encoded by a dispersed gene family.
J. DeJong (1991)
10.1159/000015072
Structure and refinement of the physical mapping of the γ-glutamylcysteine ligase regulatory subunit (GLCLR) gene to chromosome 1p22.1 within the critically deleted region of human malignant mesothelioma
J.-M. Rozet (1998)
10.1101/GAD.13.1.76
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain.
K. Itoh (1999)
10.1136/thx.53.12.1018
Contribution of genetic factors other than CFTR to disease severity in cystic fibrosis
J. Hull (1998)
10.1128/MCB.15.7.3892
Role of cysteine residues in regulation of p53 function.
R. Rainwater (1995)
10.1016/S0014-5793(98)00410-4
Characterisation of γ‐glutamylcysteine synthethase‐heavy subunit promoter: a critical role for AP‐1
I. Rahman (1998)
10.1016/S0009-2797(97)00148-8
Thioredoxin redox control of cell growth and death and the effects of inhibitors.
G. Powis (1998)
10.1016/S0891-5849(01)00530-5
Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation.
V. Hudson (2001)
10.1073/pnas.152168599
Glutathionylation of human thioredoxin: A possible crosstalk between the glutathione and thioredoxin systems
S. Casagrande (2002)
10.1159/000134202
Assignment of the human gene (GLCLR) that encodes the regulatory subunit of gamma-glutamylcysteine synthetase to chromosome 1p21.
E. Sierra-Rivera (1996)
10.1097/00005072-199603000-00001
Neuropathology of Parkinson's Disease
L. Forno (1996)
10.1093/JNCI/94.12.936
Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer.
J. Stoehlmacher (2002)
10.1002/IJC.2910580613
Formation of 8‐hydroxy‐2′‐deoxyguanosine and 4‐hydroxy‐2‐nonenal‐modified proteins in human renal‐cell carcinoma
K. Okamoto (1994)
10.1074/jbc.273.28.17477
Reactive Oxygen Species- and Dimerization-induced Activation of Apoptosis Signal-regulating Kinase 1 in Tumor Necrosis Factor-α Signal Transduction*
Y. Gotoh (1998)
10.1152/JAPPL.1999.87.1.438
Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis.
J. H. Roum (1999)
10.1074/jbc.274.5.3182
Direct Association with Thioredoxin Allows Redox Regulation of Glucocorticoid Receptor Function*
Y. Makino (1999)
10.1073/PNAS.96.13.7220
Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target.
P. Jakobsson (1999)
10.1073/PNAS.97.10.5101
Glutathione synthesis is essential for mouse development but not for cell growth in culture.
Z. Shi (2000)
10.1074/JBC.270.20.11977
Identification of a Second Region Upstream of the Mouse Heme Oxygenase-1 Gene That Functions as a Basal Level and Inducer-dependent Transcription Enhancer (*)
J. Alam (1995)
10.1096/fasebj.13.12.1481
Redox regulation of c‐Jun DNA binding by reversible S‐glutathiolation
P. Klatt (1999)
10.1046/j.1471-4159.1996.67052164.x
Effect of Buthionine Sulfoximine, a Synthesis Inhibitor of the Antioxidant Glutathione, on the Murine Nigrostriatal Neurons
J. Andersen (1996)
10.1073/PNAS.86.15.5974
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.
E. Duh (1989)
10.1016/S0278-5846(96)00103-0
Reduced intravenous glutathione in the treatment of early parkinson's disease
G. Sechi (1996)
10.1093/emboj/18.5.1321
Regulation of JNK signaling by GSTp
V. Adler (1999)
10.1002/9780470123034.CH5
The isoenzymes of glutathione transferase.
B. Mannervik (1985)
10.1074/JBC.M005561200
Glutathione S-Transferase Mu Modulates the Stress-activated Signals by Suppressing Apoptosis Signal-regulating Kinase 1*
S. Cho (2001)
10.1183/09031936.96.09020334
Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress.
R. Brown (1996)
The glutathione S-transferases: influence of polymorphism on cancer susceptibility.
R. Strange (1999)
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.
G. Barbaro (1996)
10.1073/PNAS.87.11.4063
Augmentation of glutathione in the fluid lining the epithelium of the lower respiratory tract by directly administering glutathione aerosol.
R. Buhl (1990)
10.1074/JBC.273.24.14683
An electrophile 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.
Moinova Hr (1998)
10.1042/BJ2550079
The structure of the human glutathione S-transferase pi gene.
I. Cowell (1988)
10.1152/ajpendo.1999.276.2.E326
Mechanisms involved in the regulation of key enzymes of cysteine metabolism in rat liver in vivo.
D. L. Bella (1999)
10.1016/s0021-9258(18)46868-8
Biochemical characterization of Drosophila glutathione S-transferases D1 and D21.
A. Tang (1994)



This paper is referenced by
Review Glutathione synthetase deficiency
R. Njålsson (2005)
10.1967/s002449911006
68Ga-Glutathione radio-complex as a new diagnostic probe for targeting colon cancer in rats.
Sumeera Sidiq (2019)
10.1136/gut.2010.225854
Prospective study of serum cysteine levels and oesophageal and gastric cancers in China
G. Murphy (2011)
10.3109/00498254.2012.732714
Evaluation of drug-induced injury and human response in precision-cut tissue slices
A. Vickers (2013)
10.1016/J.SNB.2014.03.055
A selective naked-eye detection and determination of cysteine using an indicator-displacement assay in urine sample
H. Khajehsharifi (2014)
10.1111/J.1439-0426.2008.01128.X
Content of cysteine, reduced and oxidized glutathione in spermatozoa of representatives of Acipenseriformes (Acipenser baerii and A. ruthenus) as well as teleosts (Perca fluviatilis and Sander lucioperca)
Karel Stejskal (2008)
10.1016/j.mrgentox.2014.09.009
Genotoxicity assessment of cerium oxide nanoparticles in female Wistar rats after acute oral exposure.
M. Kumari (2014)
10.1371/journal.pone.0105181
Global Metabolomic Analysis of Human Saliva and Plasma from Healthy and Diabetic Subjects, with and without Periodontal Disease
V. Barnes (2014)
10.1016/J.TET.2016.12.049
A novel cyanobiphenyl benzothiazole-based fluorescent probe for detection of biothiols with a large Stokes shift and its application in cell imaging
Song Chen (2017)
10.1007/s10895-020-02618-8
High-sensitivity Detection of Cysteine and Glutathione Using Au Nanoclusters Based on Aggregation-induced Emission.
Y. Zhang (2020)
10.1016/j.colsurfa.2020.125466
Ce-doped ZnCo2O4 nanospheres: synthesis, double enzyme-like performances, catalytic mechanism and fast colorimetric determination for Glutathione
Dexin Yin (2020)
10.1007/978-3-319-99037-8_16
Utilisation of Tetraphenylethene-Derived Probes with Aggregation-Induced Emission Properties in Fluorescence Detection of Biothiols
M. Liu (2019)
10.1016/j.bmcl.2018.11.040
A thiol-inducible and quick-response DNA cross-linking agent.
Y. Xu (2019)
10.1155/2019/2847961
“Turn-On” Fluorescent Assay of Biothiols Based on Nitrogen-Rich Polymer Carbon Nanostrips and Its Application in Cell Imaging
Xiangying Meng (2019)
10.1016/J.SNB.2018.01.016
Meso-heteroaryl BODIPY dyes as dual-responsive fluorescent probes for discrimination of Cys from Hcy and GSH
J. Zhang (2018)
10.1007/S10404-017-1938-Z
Sensitive analysis of glutathione in bacteria and HaCaT cells by polydopamine/gold nanoparticle-coated microchip electrophoresis via online pre-concentration of field-amplified sample stacking
Y. Zhang (2017)
10.1016/j.watres.2018.07.065
The impact of disinfection Ct values on cytotoxicity of agricultural wastewaters: Ozonation vs. chlorination.
S. Dong (2018)
STATUS OF LIPID PEROXIDATION AND ANTIOXIDANT PROTECTION SYSTEM IN WOMEN OF REPRODUCTIVE AGE WITH VIRAL HEPATITIS A
Maria Rashidova (2015)
10.31989/FFHD.V2I3.99
Anti-ulcer activity of Ipomoea batatas tubers (sweet potato)
Vandana Panda (2012)
Evaluation of oxyclozanide and niclosamide combination as alternative antiparamphistomal therapy in buffaloes
Hazem M. Shaheen (2013)
Efeito de nanopartículas de ouro associadas à N-acetilcisteína sobre lesão pulmonar aguda induzida por carragenina em ratos
Leandro de Costa da Silva (2013)
10.1007/s00604-017-2603-7
Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica nanoparticles and target induced release of glucose measured with a portable glucose meter
Qingqing Tan (2017)
10.1039/c4cc07757a
A multi-functional probe to discriminate Lys, Arg, His, Cys, Hcy and GSH from common amino acids.
X. Lu (2015)
10.1016/j.toxrep.2014.06.003
Effect of Nɛ-carboxymethyllysine on oxidative stress and the glutathione system in beta cells
Daniëlle M. P. H. J. Boesten (2014)
10.1111/jpn.13005
Effects of dietary supplemental methionine source and betaine replacement on the growth performance and activity of mitochondrial respiratory chain enzymes in normal and heat‐stressed broiler chickens
Fatemeh Sahebi Ala (2019)
10.1007/s10571-011-9795-x
Flavonoid Baicalein Modulates H2O2-Induced Mitogen-Activated Protein Kinases Activation and Cell Death in SK-N-MC Cells
M. Moslehi (2011)
10.1016/j.etap.2016.05.027
Profenofos induced biochemical alterations and in silico modelling of hatching enzyme, ZHE1 in zebrafish (Danio rerio) embryos.
R. Pamanji (2016)
10.1016/j.ejmech.2016.02.060
Toward overcoming cisplatin resistance via sterically hindered platinum(II) complexes.
H. Yu (2016)
10.1039/c4an00639a
Constructing a fluorescent probe for specific detection of cysteine over homocysteine and glutathione based on a novel cysteine-binding group but-3-yn-2-one.
Y. Liu (2014)
10.1016/j.steroids.2014.06.003
Selective estrogen-induced apoptosis in breast cancer
I. Obiorah (2014)
10.1016/J.SNB.2014.04.006
Indirect colorimetric detection of glutathione based on its radical restoration ability using carbon nanodots as nanozymes
M. Shamsipur (2014)
10.1016/j.neuro.2018.10.004
Neurobehavioral and oxidative stress alterations following methylmercury and retinyl palmitate co‐administration in pregnant and lactating rats and their offspring
Pedro Espitia-Pérez (2018)
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