Enzymology of Microsomal Glutathione S-Transferase

Andersson, Claes; Mosialou, Erifili; Weinander, Rolf; Morgenstern, Ralf

doi:10.1016/s1054-3589(08)61028-5

Cited by 81 publications

(52 citation statements)

References 49 publications

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“…GSTs are considered to be ubiquitous enzymes, representing ~3% of all microsomal proteins, a high level of expression similar to that in the liver (17). Not surprisingly, we found MGST1 to be particularly abundant in the RPE and liver and to constitute a major immunogenic antigen in RPE microsomes.…”

Section: Role Of Mgst1 In the Rpementioning

confidence: 49%

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging^,

2004

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High oxygen tension, exposure to light, and the biochemical events of vision generate significant oxidative stress in the retina and the retinal pigment epithelium (RPE). Understanding the mechanisms and basis of susceptibility to progressive retinal diseases involving oxidative damage such as age-related macular degeneration (AMD) remains a major challenge. Here microsomal glutathione S-transferase (MGST1) is shown to be a dominant, highly expressed enzyme in bovine and mouse RPE microsomes that displays significant reduction activity toward synthetic peroxides, oxidized RPE lipids, and oxidized retinoids. This enzymatic reduction activity (GPx) can be partially neutralized with a monoclonal anti-MGST1 antibody developed in this study. MGST1-transfected HEK293 cells exhibited greater viability (70 ± 4% survival) compared with untransfected control cells (46 ± 4% survival) when challenged with 20μM H 2 O 2 , and greater viability of MGST1-transfected cells following challenge with oxidized docosahexaenoic acid was also observed. Cultured ARPE19 cells transfected with silencing MGST1 siRNAs exhibited lower expression of MGST1 (12% and 26% of the controls) and significantly lower GPx activity (44 ± 13%) and, thus, were more susceptible to oxidative damage. Immunoblotting revealed that the in vivo expression of MGST1 in mouse RPE decreases 3-4-fold with age, to trace levels in 18-month-old mice. GPx activity in the RPE was also found to be reduced in 12-month-old mice to ~67%. These results support an important protective function for MGST1 against oxidative insult in the RPE that decreases with age and suggest that this enzyme may play a role in the development of age-related diseases such as AMD.Aging of the retinal pigment epithelium (RPE) 1 involves many biochemical changes and alterations in the kinetics of physiological renewal of the photoreceptor cells. The apparent † This research was supported by NIH Grants EY09339, EY13385, EY06603, and EY14239, a grant from Research to Prevent Blindness, Inc. (RPB), to the Department of Ophthalmology at the University of Washington, the Stargardt and Retinal Eye Disease Fund, and a grant from the E. K. Bishop Foundation. K.P. is a RPB Senior Investigator. ‡ GenBank Accession Number AY334548.* Address correspondence to this author at the Department of Ophthalmology, University of Washington, Box 356485, Seattle,. E-mail:palczews@u.washington.edu.. § Department of Ophthalmology, University of Washington. || Cole Eye Institute, Cleveland Clinic Foundation. ⊥ Department of Pharmacology, University of Washington. # Department of Chemistry, University of Washington.1 Abbreviations: AMD, age-related macular degeneration; CEP, ω-(2-carboxyethyl)pyrrole; CDNB, 1-chloro-2,4-dinitrobenzene; (c)-GST, (cytosolic) glutathione S-transferase; DHA, docosahexaenoic acid; DM, dodecyl β-maltoside; DMSO, dimethyl sulfoxide; GPx, glutathione peroxidase; GR, glutathione reductase; GST, glutathione S-transferase; GSH, reduced glutathione; GSSG, oxidized glutathione; 13(S)-HpODE, 13(S)-...

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Section: Role Of Mgst1 In the Rpementioning

confidence: 49%

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging^,

2004

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“…In mammals, at least six classes of soluble enzyme, designated Theta, Kappa, Alpha, Mu, Pi and Sigma, have been described [1][2][3][4]. Three membrane-bound forms that have evolved separately from the cytosolic transferases are referred to as microsomal GST, leukotriene C % synthase and microsomal GST II [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse: Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human

Sherratt

Pulford

Harrison

et al. 1997

Biochemical Journal

136

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The cDNA encoding human glutathione S-transferase (GST) T1 has been expressed as two recombinant forms in Escherichia coli that could be purified by affinity chromatography on either IgGSepharose or nickel-agarose ; one form of the transferase was synthesized from the pALP 1 expression vector as a Staphylococcus aureus protein A fusion, whereas the other form was synthesized from the pET-20b expression vector as a C-terminal polyhistidine-tagged recombinant. The yields of the two purified recombinant proteins from E. coli cultures were approx. 15 mg\l for the protein A fusion and 25 mg\l for the C-terminal polyhistidine-tagged GST T1-1. The purified recombinant proteins were catalytically active, although the protein A fusion was typically only 5-30 % as active as the histidine-tagged GST. Both recombinant forms could catalyse the conjugation of glutathione with the model substrates 1,2-epoxy-3-(4h-

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“…In Phase II, the glutathione S-transferases (GSTs) allow these metabolites to combine with polar endogenous molecules to form conjugation products that are excreted quickly [100]. With this reaction, the solubility of dangerous compounds increases for their excretion [101]. In this same Phase II of the enzymatic de-intoxication, many electrophilic metabolites, such as xenobiotic derivates and endogenous molecules, such as aflatoxins, have carcinogenic and genotoxic effects [102][103][104].…”

Section: Glutathione S-transferase (Gst) Enzymesmentioning

confidence: 99%

Do Gastroenterologists Consider Aflatoxins as Origin of Digestive System Cancers?

Carvajal-Moreno¹

2017

J Pharmacovigil

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Aflatoxins are important etiological factors for cancers in the digestive system that have not been extensively studied. The present review describes reports of the presence of aflatoxins in cancers of the esophagus, stomach, pancreas, liver, colon and rectum. The presence of AFB 1 -FAPY adducts and mutations in codon 249 of the tumor suppressor gene p53 in colorectal cancer tumors and Ki-ras activation by point mutation in pancreas cancer are reliable criteria to accept AFs as an important etiological factor. The Ministries of Health of the different countries should perform more preventive practices on crops in the field and in warehouses; they should chemically analyze aflatoxins in fresh and industrialized foods for humans and feeds for animals to avoid the presence of these dangerous toxins.

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Enzymology of Microsomal Glutathione S-Transferase

Cited by 81 publications

References 49 publications

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging^,

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging^,

Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse: Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human

Do Gastroenterologists Consider Aflatoxins as Origin of Digestive System Cancers?

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Enzymology of Microsomal Glutathione S-Transferase

Cited by 81 publications

References 49 publications

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging,

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging,

Evidence that human class Theta glutathione S-transferase T1-1 can catalyse the activation of dichloromethane, a liver and lung carcinogen in the mouse: Comparison of the tissue distribution of GST T1-1 with that of classes Alpha, Mu and Pi GST in human

Do Gastroenterologists Consider Aflatoxins as Origin of Digestive System Cancers?

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Product

Resources

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Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging^,

Microsomal Glutathione S-Transferase 1 in the Retinal Pigment Epithelium: Protection against Oxidative Stress and a Potential Role in Aging^,