Cited by 1,266Sulfur Compounds in BiologyGlutathione Transferases and PolymorphismsRedox biology and oxidative stress

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Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

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Lushchak, Volodymyr I.·2012·Journal of Amino Acids

DOI 10.1155/2012/736837PMC PMC3303626

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Abstract

Glutathione (GSH) is a tripeptide, which has many biological roles including protection against reactive oxygen and nitrogen species. The primary goal of this paper is to characterize the principal mechanisms of the protective role of GSH against reactive species and electrophiles. The ancillary goals are to provide up-to-date knowledge of GSH biosynthesis, hydrolysis, and utilization; intracellular compartmentalization and interorgan transfer; elimination of endogenously produced toxicants; involvement in metal homeostasis; glutathione-related enzymes and their regulation; glutathionylation of sulfhydryls. Individual sections are devoted to the relationships between GSH homeostasis and pathologies as well as to developed research tools and pharmacological approaches to manipulating GSH levels. Special attention is paid to compounds mainly of a natural origin (phytochemicals) which affect GSH-related processes. The paper provides starting points for development of novel tools and provides a hypothesis for investigation of the physiology and biochemistry of glutathione with a focus on human and animal health.

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“Moreover, tumors also present high levels of GSH, as well as glutathione-S-Sglutathione (GSSG) and GSH-conjugates in their interstitial fluid [44-47], which can be transferred intracellularly and provide the basis for the salvage cycle of recycling the excreted GSH and GSSG by the original cell or by other cells [44,4…”
Background
Gibbs Energy of Superoxide Dismutase Heterodimerization Accounts for Variable Survival in Amyotrophic Lateral Sclerosis
Shi, Y., Acerson, M. J., Abdolvahabi, A., Mowery, R. A., & Shaw, B. F. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b01742 · Cited by 22
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“The chosen biomarkers are one of the most acknowledged indicators of oxidative stress, what is justified by results of numerous studies (e.g. Mates 2000; Osman et al. 2007; Niki 2008; Lushchak 2012).”
Background
Anxiolytic effect of anacardic acids from cashew ( Anacardium occidentale ) nut shell in mice
Júnior, A. L. G., Tchekalarova, J. D., Machado, K. D. C., Moura, A. K. S., Paz, M. F. C. J., da Mata, A. M. O. F., Nogueira, T. R., Islam, M. T., Rios, M. A. D. S., Citó, A. M. D. G. L., et al. (2018) · IUBMB Life · doi:10.1002/iub.1738 · Cited by 21
“GSH is a tripeptide (c-glutamyl-cysteinyl-glycine) responsible for the direct removal of ROS and also acts as a cofactor for ROS-neutralizing enzyme glutathione peroxidase (42), while CAT is an enzyme responsible for the conversion of hydrogen peroxide (H2O2) into water (H2O) and oxygen (O2) (43).”
Background
An Adverse Outcome Pathway (AOP) for forestomach tumors induced by non-genotoxic initiating events
Proctor, D. M., Suh, M., Chappell, G. A., Borghoff, S. J., Thompson, C. M., Wiench, K., Finch, L., & Ellis‐Hutchings, R. G. (2018) · Regulatory Toxicology and Pharmacology · doi:10.1016/j.yrtph.2018.04.016 · Cited by 21
Inhibition of NRF2 signaling and increased reactive oxygen species during embryogenesis in a rat model of retinoic acid-induced neural tube defects
Liu, D., Xue, J., Liu, Y., Gu, H., Wei, X., Ma, W., Luo, W., Ma, L., Jia, S., Dong, N., et al. (2018) · NeuroToxicology · doi:10.1016/j.neuro.2018.09.005 · Cited by 23
In vivo toxicometabolomics reveals multi-organ and urine metabolic changes in mice upon acute exposure to human-relevant doses of 3,4-methylenedioxypyrovalerone (MDPV)
Araújo, A. M., Carvalho, M. C., Costa, V. M., Duarte, J. A., Dinis‐Oliveira, R. J., Bastos, M. D. L., de Pinho, P. G., & Carvalho, F. D. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02949-2 · Cited by 21
“However, its antioxidant potential is the most well-known property, providing cellular protection due to its ability to neutralize reactive oxygen and nitrogen species (ROS/RNS) and electrophiles and to act as a cofactor for several antioxidant enzymes (Lushchak 2012).”
Background
Altered metabolic homeostasis between vitamin D and long chain polyunsaturated fatty acids in preeclampsia
Nandi, A. A., Wadhwani, N. S., & Joshi, S. (2017) · Medical Hypotheses · doi:10.1016/j.mehy.2017.01.009 · Cited by 21
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Glutathione-related genetic polymorphisms are associated with mercury retention and nephrotoxicity in gold-mining settings of a Colombian population
Pérez, O. M. M., Flórez-Vargas, O., Cruz, G. R., González, F. R., Rocha-Muñoz, L. P., & Rodríguez, L. H. S. (2021) · Scientific Reports · doi:10.1038/s41598-021-88137-3 · Cited by 20
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Alışık, M., Alışık, T., Nacir, B., Neşeli̇oğlu, S., Işık, İ. G., Koyuncu, P., & Erel, Ö. (2021) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2021.04.023 · Cited by 22
Hericium erinaceus (Bull.) Pers. Ethanolic Extract with Antioxidant Properties on Scopolamine-Induced Memory Deficits in a Zebrafish Model of Cognitive Impairment
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“Glutathione is an essential component of the cellular antioxidant defense system and is directly involved in maintaining cellular redox homeostasis [52].”
Background
Design of Nanoparticles in Cancer Therapy Based on Tumor Microenvironment Properties
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“Additionally, higher levels of ROS are connected to a higher level of antioxidants [96].”
Background
Metabolomics of the anti-inflammatory effect of Pueraria lobata and Pueraria lobata var. Thomsonii in rats
Xi, C., Zhang, M., Li, B., Meng, X., Xu, S., Du, H. X., Wang, X., Xu, J., Ke, H., Cui, Y., et al. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116144 · Cited by 20
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“Research has shown that environmental stresses that involve the osmotic regulation system can cause the formation of free radicals 57,96 .”
The mitochondrial uncoupler 2,4-dinitrophenol attenuates sodium nitroprusside-induced toxicity in Drosophila melanogaster: Potential involvement of free radicals
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Self-citation
Critical role of cellular glutathione homeostasis for trivalent inorganic arsenite-induced oxidative damage in human bronchial epithelial cells
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“The GSH is a biological antioxidant present in high concentrations, and offers protection against oxidative damage [34, 45, 46].”
Background
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“Several in vitro and in vivo studies have shown that NAC induces the intracellular biosynthesis of glutathione (GSH), a well-known direct antioxidant and substrate for several antioxidant enzymes [13].”
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“This isoform is present in every cell and also in the cytosol, mitochondria, and peroxysomes.”
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“Along with evidence of oxidative damage, we found impairment of the GSH-dependent system, which is critical in antioxidant response [71,72].”
BackgroundInfluential
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“Glutathione (GSH) is an abundant thiol-containing compound in most cells, and is found in the millimolar range in the cytoplasm of healthy cells, making it an excellent candidate for GSH-triggered siRNA release [8].”
Background
A high-fat diet differentially regulates glutathione phenotypes in the obesity-prone mouse strains DBA/2J, C57BL/6J, and AKR/J
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“The protective capacity of this molecule is attributable in part to its abilities to directly neutralize reactive oxygen species and to serve as a cofactor for reactive oxygen species metabolizing enzymes [1].”
Background
The problem of assessing the viability of invasive species in the conditions of the steppe zone of Ukraine
Holoborodko, К. К., Маренков, О. М., Gorban, V. A., & Voronkova, Y. (2016) · Biosystems Diversity · doi:10.15421/011663 · Cited by 18
“Actually glutathione not only protects the cell from such toxic agents as free radicals, but also determines the redox status of the intracellular environment generally (Anderson, 1998; Lushchak, 2012).”
Background
Effect of dietary vitamin E and selenium supplementation on semen quality in Cairn Terriers with normospermia
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“GSH- PX serves as an intracytoplasmatic antioxidant and is predominantly located in the mitochondria (Batcioglu, Ozturk, Karagozler, & Karatas, 2002; Lushchak, 2012; Sunde & Hoekstra, 1980).”
BackgroundInfluential
Changes in the Fecal Metabolome Are Associated with Feeding Fiber Not Health Status in Cats with Chronic Kidney Disease
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“Because the antioxidant glutathione conjugates with amino acids to form cysteinylglycine [19], reduced concentrations of cysteinylglycine in the feces of CKD cats consuming scFOS may suggest increased intestinal concentrations of glutathione, which is known to provide intestinal mucosal health benefits [20].”
Background
Reactive oxygen species, glutathione, and vitamin E concentrations in dogs with hemolytic or nonhemolytic anemia
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“The duration of hemolysis was unknown in these cases, so future studies should investigate the effect of acute vs chronic hemolysis on the plasma and RBC fractions of GSH.”
BackgroundInfluential
Size and ligand effects of gold nanoclusters in alteration of organellar state and translocation of transcription factors in human primary astrocytes
Gran, E. R., Bertorelle, F., Fakhouri, H., Antoine, R., Bakulić, M. P., Maršić, Ž. S., Bonačić‐Koutecký, V., Blain, M., Antel, J. P., & Maysinger, D. (2021) · Nanoscale · doi:10.1039/d0nr06401g · Cited by 18
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Mechanisms of nitric oxide generation in living systems
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Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS
El‐Sherbiny, M., Fahmy, E. K., Eisa, N. H., Said, E., Elkattawy, H. A., Ebrahim, H. A., Elsherbiny, N. M., & Ghoneim, F. M. (2021) · Molecules · doi:10.3390/molecules26247684 · Cited by 20
“With regard to γ-GCS, reduced glutathione (GSH) is a ubiquitous tripeptide thiol, vital intracellular, and extracellular protective antioxidant, playing a crucial role in the detoxification of various xenobiotics [54].”
Background

Authors: Lushchak, V. I.
Affiliations: Vasyl Stefanyk Carpathian National University (UA)
Corresponding author: Lushchak, Volodymyr I.
ORCID: Lushchak, Volodymyr I.
Venue: Journal of Amino Acids
Publisher: Wiley
Published: 2012-02-28
Volume: 2012
Pages: 1-26
ISSN: 2090-0104 (ISSN-L)
2090-0112
DOI: 10.1155/2012/736837
PMC: PMC3303626
OpenAlex: W2043037824
Cited by: 1,266
References: 283
Citations by year: 2026: 70 · 2025: 117 · 2024: 119 · 2023: 126 · 2022: 125 · 2021: 131 · 2020: 110 · 2019: 79 · 2018: 76 · 2017: 93 · 2016: 64 · 2015: 64 · 2014: 52 · 2013: 29 · 2012: 7
FWCI: 20.84
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (unspecified)
Locations: Journal of Amino Acids (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Ministry of Education and Science of Ukraine (0106U002245)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: glutathione, glutathione homeostasis, reactive oxygen species, reactive nitrogen species, glutathione synthesis, glutathione metabolism, metal homeostasis, glutathionylation, sulfhydryl groups, phytochemicals, disease pathology

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Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions

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