Purification and characterization of a labile rat glutathione transferase of the Mu class

Kispert, Andreas; Meyer, David J.; Lalor, E.; Coles, Brian; Ketterer, Brian

doi:10.1042/bj2600789

Cited by 48 publications

(45 citation statements)

References 30 publications

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“…Hepatocytes were treated with ␣-amanitin (2 g/ml) in the absence or presence of 100 units/ml IL-1. Total RNA isolated from cells 0, 4,8,12,14,16,18,20,24, and 28 h following ␣-amanitin treatment were analyzed by Northern blot and hybridized with the rGSTM1 probe as described under "Experimental Procedures." rGSTM1 mRNA level was related to 18 S rRNA levels, and values are represented as the log of the untreated controls.…”

Section: Figmentioning

confidence: 99%

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Mahéo¹,

Antras-Ferry

Morel

et al. 1997

Journal of Biological Chemistry

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The influence of various cytokines on the expression of glutathione S-transferases (GSTs) was investigated in rat hepatocytes in primary culture. Only treatment of hepatocytes with interleukin-1␤ (IL-1) was effective, resulting in a marked decrease in GSTs. Steady-state mRNA levels of rGSTA2 and M1 were strongly downregulated by IL-1 in a dose-dependent manner after a 24-h exposure while rGSTP1 mRNA level was increased by a 48-h treatment. Similar effects of IL-1 were observed at the protein level. The response to IL-1 appeared to be specific for each subunit within GST gene families. In addition, IL-1 strongly suppressed the induction of rGSTA2 by 3-methylcholanthrene, oltipraz (a synthetic derivative of 1,2-dithiole-3-thione), and phenobarbital and that of rGSTM1 by oltipraz and phenobarbital, whereas it was ineffective on rGSTP1 induction by these compounds. Using in vitro nuclear run-on transcription assay and Northern blot analysis of ␣-amanitin-treated cells, IL-1-mediated rGSTM1 mRNA decrease was found to result from mRNA destabilization. These results provide the first demonstration that IL-1 regulates some major GST subunits in hepatocytes by a post-transcriptional mechanism.

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Section: Figmentioning

confidence: 99%

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Mahéo¹,

Antras-Ferry

Morel

et al. 1997

Journal of Biological Chemistry

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“…3B). Cyanogen bromide cleavage of GST11-11 (Yo or rG-STM5) (17) yielded an identical sequence between the putative CNBr cleavage site methionine residues of this particular peptide 9, and Hsieh et al (22) recently found this peptide after protease digestion of a rat testicular GST. Those authors were apparently unaware that the N-terminal sequence of this subunit extends beyond that of other Mu-class subunits and assumed that this peptide was near the N terminus of the GST with the first methionine at position 2.…”

Section: Iodo[mentioning

confidence: 99%

“…Indeed, this study establishes that a labile and poorly characterized rat subunit previously designated as Yo or GST 11 (14,16,17) and mouse mGSTM5 are similar to the human hGSTM3 subunit in terms of structure, catalytic mechanisms, tissueselective expression patterns, and other unique properties.…”

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confidence: 99%

Rationale for Reclassification of a Distinctive Subdivision of Mammalian Class Mu Glutathione S-Transferases That Are Primarily Expressed in Testis

Rowe¹,

Patskovsky

Patskovska

et al. 1998

Journal of Biological Chemistry

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A rat testicular Mu-class glutathione S-transferase (GST) resolved by reversed-phase high performance liquid chromatography cross-reacted with peptide sequence-specific antisera raised against the human hGSTM3 subunit. Electrospray ionization mass spectrometry indicated that this rat GST subunit (designated rGSTM5 in this report) has a significantly greater molecular mass (26,541 Da) than the other rat GST subunits. The mouse homologue (mGSTM5 subunit) was also identified and characterized by high performance liquid chromatography and electrospray ionization mass spectrometry. Sequence analysis of rGSTM5 peptide fragments and the sequence deduced from a cDNA clone showed that the protein is highly homologous to the hGSTM3 and murine mGSTM5 subunits. All three GSTs of this subclass have N-and C-terminal extensions with Cterminal cysteine residues, but the two penultimate amino acids near the C terminus are divergent in the three species. The proteins of this class Mu subfamily have similar catalytic specificities and mechanisms, are all cysteine rich, are found mainly in testis, and share characteristics that distinguish them from other GSTs. Moreover, the rGSTM5 subunit isolated from rat testis was not found in heterodimeric combination with other common Mu-class GST subunits. As the rGSTM5, mGSTM5, and hGSTM3 subunits are structurally more closely related to each other than they are to other Mu GSTs, it is proposed that they be considered a functionally distinct and separate subfamily within class Mu. The identification of this unique mammalian GST subclass could advance strategies for interspecies comparisons of GSTs and provides a rodent model for studies on functions and regulatory mechanisms for human GSTs.

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“…PB was dissolved in phosthey are not required to be accepted pharmaceuticals. phate 21 Tissues or cells were treated with MC (20 mg/kg/day intraperitoneally, inwere homogenized in buffer A (150 mmol/L of KCl, 50 mmol/ jected in corn oil [2 mL/kg] for 3 or 5 days) 9 or with OPZ, L of phenylmethanesulfonyl fluoride, 1 mmol/L of ethylenediwhich was incorporated into the diet at a final concentration aminetetraacetic acid, and 2 mmol/L of dithiothreitol in 10 of 0.075% (wt/wt) for 3 or 5 days. 10 Four animals were used mmol/L of potassium phosphate buffer, pH 7.0), and the sufor each experimental condition and were killed 24 hours pernatant cytosol fraction was recovered.…”

mentioning

confidence: 99%

A comparison of the effect of inducers on the expression of glutathione- S -transferases in the liver of the intact rat and in hepatocytes in primary culture

et al. 1996

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uid chromatography (HPLC) analysis of GST subunits. Recently, we used human hepatocytes in primary cul-HPLC also showed an induction of subunit 10 at the ture to study the effects of inducers of glutathione-Sprotein level of which the mRNA was not analyzed. Our transferases (GSTs) in the expectation that information results show that rat hepatocytes in primary culture obtained can be used to predict the value of particular prove to be a good model for the effect of inducers on inducers for use in the chemoprevention of cancer and both the expression of GST mRNA and protein levels other toxicities. However, in vitro human studies cannot in the rat liver in vivo. The demonstration of this good readily be confirmed by studies in vivo. This problem correlation in the rat with respect to increases gives supdoes not arise in experimental animals. In the current port for the use of human hepatocytes for predictive studies, the response of male rat hepatocytes in primary studies of chemoprotection in human pharmacology. culture to the following inducers of GST isoenzymes has (HEPATOLOGY 1996;23:881-887.) been determined: 3-methylcholanthrene (MC); phenobarbital (PB); 1,2-dithiole-3-thione and its 5-(2-pyrazi- nyl)-4-methyl derivative, oltipraz (OPZ), and the results have been compared with induction obtained in liversThe glutathione-S-transferases (GSTs) represented of MC-and OPZ-treated rats. Each type of inducer was by four multigene families (a, m, p, and u) provide profound to elicit a different response. In vitro, phenobarbi-tection against the genotoxicity and cytotoxicity of a tal increased messenger RNA (mRNA) levels of subunits number of electrophiles.1,2 In the rat, GST class a con1b and 3 after 12 and 72 hours, respectively; MC had tains subunits 1a, 1b, 2, 8 and 10; class m, subunits 3, a rapid effect on GST a class mRNAs (bringing about 4, 6, 9, and 11; class p, subunit 7 1 ; and class u, subunits increase after only 2 hours of treatment), increased sub-5, 12, and 13. 2,3unit 7 mRNA slightly, and had no effect on mu class Like other enzymes of xenobiotic metabolism they mRNAs; dithiolethiones induced both subunit 1b and 7 are most abundant in the liver and are inducible by mRNAs after 4 hours and, to a much lower extent, submany xenobiotics.4 By increasing hepatic detoxication, unit 3 mRNA after 72 hours. In vivo, MC induced significantly both subunit 1b and 7 mRNAs whereas OPZ in-inducers have the potential to prevent what might othcreased significantly subunits 1b, 3 and 7 mRNA levels, erwise be serious toxic damage. For example, rats are and to a lower extent those of subunit 2, after 3 days and usually susceptible to aflatoxin B 1 (AFB 1 )-induced beyond to at least 5 days of treatment. Results obtained hepatocarcinogenesis but may become resistant after in mRNA studies were confirmed by high-pressure liq-they have been treated with chemicals that increase levels of GST. 5 This phenomenon, referred to as chemoprevention, is also believed to occur in humans. ThereAbbreviations: GST, glutathione-S-trans...

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Purification and characterization of a labile rat glutathione transferase of the Mu class

Cited by 48 publications

References 30 publications

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Modulation of Glutathione S-Transferase Subunits A2, M1, and P1 Expression by Interleukin-1β in Rat Hepatocytes in Primary Culture

Rationale for Reclassification of a Distinctive Subdivision of Mammalian Class Mu Glutathione S-Transferases That Are Primarily Expressed in Testis

A comparison of the effect of inducers on the expression of glutathione- S -transferases in the liver of the intact rat and in hepatocytes in primary culture

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