Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution

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Abstract

Glutathione transferase P1-1 (GSTP1-1) is expressed in some human tissues and is abundant in mammalian erythrocytes (here termed e-GST). This enzyme is able to detoxify the cell from endogenous and exogenous toxic compounds by using glutathione (GSH) or by acting as a ligandin. This review collects studies that propose GSTP1-1 as a useful biomarker in different fields of application. The most relevant studies are focused on GSTP1-1 as a biosensor to detect blood toxicity in patients affected by kidney diseases. In fact, this detoxifying enzyme is over-expressed in erythrocytes when unusual amounts of toxins are present in the body. Here we review articles concerning the level of GST in chronic kidney disease patients, in maintenance hemodialysis patients and to assess dialysis adequacy. GST is also over-expressed in autoimmune disease like scleroderma, and in kidney transplant patients and it may be used to check the efficiency of transplanted kidneys. The involvement of GSTP in the oxidative stress and in other human pathologies like cancer, liver and neurodegenerative diseases, and psychiatric disorders is also reported. Promising applications of e-GST discussed in the present review are its use for monitoring human subjects living in polluted areas and mammals for veterinary purpose.

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Most cited references 171

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Glutathione transferases.

John Hayes, Jack U. Flanagan, Ian R Jowsey (2005)

This review describes the three mammalian glutathione transferase (GST) families, namely cytosolic, mitochondrial, and microsomal GST, the latter now designated MAPEG. Besides detoxifying electrophilic xenobiotics, such as chemical carcinogens, environmental pollutants, and antitumor agents, these transferases inactivate endogenous alpha,beta-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. These enzymes are also intimately involved in the biosynthesis of leukotrienes, prostaglandins, testosterone, and progesterone, as well as the degradation of tyrosine. Among their substrates, GSTs conjugate the signaling molecules 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2) and 4-hydroxynonenal with glutathione, and consequently they antagonize expression of genes trans-activated by the peroxisome proliferator-activated receptor gamma (PPARgamma) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2). Through metabolism of 15d-PGJ2, GST may enhance gene expression driven by nuclear factor-kappaB (NF-kappaB). Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease. Polymorphisms in human MAPEG are associated with alterations in lung function and increased risk of myocardial infarction and stroke. Targeted disruption of murine genes has demonstrated that cytosolic GST isoenzymes are broadly cytoprotective, whereas MAPEG proteins have proinflammatory activities. Furthermore, knockout of mouse GSTA4 and GSTZ1 leads to overexpression of transferases in the Alpha, Mu, and Pi classes, an observation suggesting they are part of an adaptive mechanism that responds to endogenous chemical cues such as 4-hydroxynonenal and tyrosine degradation products. Consistent with this hypothesis, the promoters of cytosolic GST and MAPEG genes contain antioxidant response elements through which they are transcriptionally activated during exposure to Michael reaction acceptors and oxidative stress.

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Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily.

D Sheehan, G. Meade, V Foley … (2001)

The glutathione transferases (GSTs; also known as glutathione S-transferases) are major phase II detoxification enzymes found mainly in the cytosol. In addition to their role in catalysing the conjugation of electrophilic substrates to glutathione (GSH), these enzymes also carry out a range of other functions. They have peroxidase and isomerase activities, they can inhibit the Jun N-terminal kinase (thus protecting cells against H(2)O(2)-induced cell death), and they are able to bind non-catalytically a wide range of endogenous and exogenous ligands. Cytosolic GSTs of mammals have been particularly well characterized, and were originally classified into Alpha, Mu, Pi and Theta classes on the basis of a combination of criteria such as substrate/inhibitor specificity, primary and tertiary structure similarities and immunological identity. Non-mammalian GSTs have been much less well characterized, but have provided a disproportionately large number of three-dimensional structures, thus extending our structure-function knowledge of the superfamily as a whole. Moreover, several novel classes identified in non-mammalian species have been subsequently identified in mammals, sometimes carrying out functions not previously associated with GSTs. These studies have revealed that the GSTs comprise a widespread and highly versatile superfamily which show similarities to non-GST stress-related proteins. Independent classification systems have arisen for groups of organisms such as plants and insects. This review surveys the classification of GSTs in non-mammalian sources, such as bacteria, fungi, plants, insects and helminths, and attempts to relate them to the more mainstream classification system for mammalian enzymes. The implications of this classification with regard to the evolution of GSTs are discussed.

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A study of the quality of life and cost-utility of renal transplantation.

Andreas Laupacis, Paul Keown, Nancy Pus … (1996)

The objective of this study was to assess the cost-utility of renal transplantation compared with dialysis. To accomplish this, a prospective cohort of pre-transplant patients were followed for up to two years after renal transplantation at three University-based Canadian hospitals. A total of 168 patients were followed for an average of 19.5 months after transplantation. Health-related quality of life was assessed using a hemodialysis questionnaire, a transplant questionnaire, the Sickness Impact Profile, and the Time Trade-Off Technique. Fully allocated costs were determined by prospectively recording resource use in all patients. A societal perspective was taken. By six months after transplantation, the mean health-related quality of life scores of almost all measures had improved compared to pre-transplantation, and they stayed improved throughout the two years of follow up. The mean time trade-off score was 0.57 pre-transplant and 0.70 two years after transplantation. The proportion of individuals employed increased from 30% before transplantation to 45% two years after transplantation. Employment prior to transplantation [relative risk (RR) = 23], graft function (RR 10) and age (RR 1.6 for every decrease in age by one decade), independently predicted employment status after transplantation. The cost of pre-transplant care ($66,782 Can 1994) and the cost of the first year after transplantation ($66,290) were similar. Transplantation was considerably less expensive during the second year after transplantation ($27,875). Over the two years, transplantation was both more effective and less costly than dialysis. This was true for all subgroups of patients examined, including patients older than 60 and diabetics. We conclude that renal transplantation was more effective and less costly than dialysis in all subgroups of patients examined.

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Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 27 July 2019

Publication date Collection: August 2019

Volume: 11

Issue: 8

Electronic Location Identifier: 1741

Affiliations

[1 ]Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy

[2 ]UOC of Internal Medicine-Center of Hypertension and Nephrology, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

[3 ]PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

[4 ]Section of Legal Medicine, Social Security and Forensic Toxicology, Department of Biomedicine and Prevention, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy

Author notes

[* ]Correspondence: riccig@ 123456uniroma2.it ; Tel.: +39-067-259-4353, Fax: +39-067-259-4328

[†]

These authors equally contributed to the work.

Author information

Annalisa Noce https://orcid.org/0000-0003-1310-3730

Giulia Marrone https://orcid.org/0000-0002-5854-2086

Nicola Di Daniele https://orcid.org/0000-0001-7671-0015

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Publisher ID: nutrients-11-01741

DOI: 10.3390/nu11081741

PMC ID: 6723968

PubMed ID: 31357662

SO-VID: cc5e4ba5-840b-4089-aef7-f1c456a6f234

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Glutathione Transferase P1-1 an Enzyme Useful in Biomedicine and as Biomarker in Clinical Practice and in Environmental Pollution

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Karger: Nutrition and Dietetics

Most cited references 171

Glutathione transferases.

Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily.

A study of the quality of life and cost-utility of renal transplantation.

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