Mammalian class theta GST and differential susceptibility to carcinogens: a review

Landi, Stefano

doi:10.1016/s1383-5742(00)00050-8

Cited by 428 publications

(304 citation statements)

References 201 publications

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“…Although unlikely, it might also reflect the null mutant genotype in 20% of the Caucasian population. 31 The SV40 T antigen-immortalized cell line SVpgC2a represents a model of a preneoplastic state of the oral epithelium. 18 -20 Eight of the 22 investigated transcripts were differentially expressed, 5 exhibited higher and 3 lower expression levels, in SVpgC2a as compared with the NOK lines.…”

Section: Discussionmentioning

confidence: 99%

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

Vondracek

Weaver

Sarang

et al. 2002

Intl Journal of Cancer

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The metabolic detoxification capacity may critically regulate the susceptibility of human tissues to cancer development. We used standardized and quantitative, reverse transcription-polymerase chain reaction (StaRT-PCR) and microarray chip techniques to analyze transcript levels of multiple detoxification enzymes in cultured normal human oral keratinocytes (NOK) and the Siman virus 40 T antigenimmortalized oral keratinocyte line SVpgC2a, viewing the latter as a model of a benign tumor state. With good agreement between the 2 methodologies, NOK and SVpgC2a were found to express transcripts for cytochrome P450 enzymes (CYPs), factors related to CYP induction and enzymes involved in conjugation reactions or detoxification of reactive oxygen. The cell types expressed similar levels of CYP 2B6/7, CYP 2E1, P450 oxidoreductase, the aryl hydrocarbon receptor nuclear translocator, sulfotransferase 1A1, sulfotransferase 1A3, epoxide hydrolase, glutathione S-transferase M3, glutathione S-transferase pi and catalase, superoxide dismutase 1, glutathione peroxidase 1 and glutathione peroxidase 3. In contrast, SVpgC2a exhibited comparatively higher levels of CYP1A1, 1B1, aryl hydrocarbon receptor, glutathione S-transferase M1, 2, 4, 5, glutathione S-transferase theta 1 and superoxide dismutase 2 and comparatively lower levels of UDP glycosyltransferase 2 and microsomal glutathione S-transferase 1. Some transcripts, e.g., CYP 2A6/7, were not detected by either standard, non quantitative RT-PCR or the above methods, whereas others were barely quantifiable by StaRT-PCR, i.e., were present at 1-10 molecules/10 6 molecules of actin. Overall, the expression analysis demonstrated presence of mRNA for multiple enzymes involved in foreign compound metabolism and detoxification pathways, including several enzymes not previously reported for oral epithelium. Generally, the comparison of NOK from 2 individuals indicated relatively similar transcript levels of these enzymes. In contrast, differences between NOK and SVpgC2a, e.g., for CYP1B1, may reflect alteration caused by immortalization and aid identification of early stage tumor markers in oral epithelium. © 2002 Wiley-Liss, Inc. Key words: oral epithelium; biotransformation; phase I and II metabolizing enzymes; mRNA expressionSeveral enzyme systems including cytochrome P450s (CYPs), conjugation enzymes and enzymes involved in detoxification of reactive oxygen species (ROS) cooperate to protect the organism against reactive agents that are potentially carcinogenic and stress inducing. 1 Oxidative metabolism (so called phase I metabolism), carried out by the CYP family of enzymes, initiate biotransformation of compounds, which do not possess functional groups suitable for conjugation and can thereby generate toxic and mutagenic/ carcinogenic intermediates. 2 Following CYP dependent oxidative activation, conjugation enzymes (involved in so called phase II metabolism) including transferases for glutathione, sulfate, acetyl moieties and glucuronic acid generally decrease the reactivity of ...

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Section: Discussionmentioning

confidence: 99%

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

Vondracek

Weaver

Sarang

et al. 2002

Intl Journal of Cancer

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“…In addition, most lack detectable activity toward CDNB, and thus can be missed if GST activity is the only means of GST isolation [54,55]. The unique activity of theta-class GSTs can be traced to the presence of the essential Ser-11, responsible for glutathione deprotonation and activation, in place of the tyrosine found in the alpha, mu, and pi class GSTs [56]. Theta-class GSTs can be further distinguished from alpha/mu/pi class isoforms because of their high affinity for glutathione (high K m ), but low affinity for glutathione-conjugates.…”

Section: Discussionmentioning

confidence: 99%

“…Theta-class GSTs can be further distinguished from alpha/mu/pi class isoforms because of their high affinity for glutathione (high K m ), but low affinity for glutathione-conjugates. The diminished product retention in the active site of theta GSTs favors increased substrate turnover in comparison to alpha/mu/pi forms, which have a greater capacity to sequester conjugated products [56]. Generally, it is believed that the thetaclass GSTs gave rise to the alpha/mu/pi classes via gene duplication events [52]; however, this has been called into question more recently [57].…”

Section: Discussionmentioning

confidence: 99%

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Proteomic identification, cDNA cloning and enzymatic activity of glutathione S-transferases from the generalist marine gastropod, Cyphoma gibbosum

Whalen¹,

Morin²,

Lin³

et al. 2008

Archives of Biochemistry and Biophysics

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Short title: Characterization of glutathione S-transferases from Cyphoma gibbosumFootnote: The nucleotide and translated amino acid sequences for C. gibbosum GSTs have been deposited in GenBank with the following accession nos. EU008563 (CgGSTM1) and EU008562 (CgGSTM2).Abbreviations footnote: CDNB, 1-chloro-2,4-dinitrobenzene; GST, glutathione S-transferase; nrDB, non-redundant database; RACE, rapid amplification of cDNA ends; RT-PCR, reverse transcriptase polymerase chain reaction 2 ABSTRACT Glutathione S-transferases (GST) were characterized from the digestive gland of Cyphoma gibbosum (Mollusca; Gastropoda), to investigate the possible role of these detoxification enzymes in conferring resistance to allelochemicals present in its gorgonian coral diet. We identified the collection of expressed cytosolic Cyphoma GST classes using a proteomic approach involving affinity chromatography, HPLC and nanospray liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two major GST subunits were identified as putative mu-class GSTs; while one minor GST subunit was identified as a putative theta-class GST, apparently the first theta-class GST identified from a mollusc. Two Cyphoma GST cDNAs (CgGSTM1 and CgGSTM2) were isolated by RT-PCR using primers derived from peptide sequences. Phylogenetic analyses established both cDNAs as mu-class GSTs and revealed a mollusc-specific subclass of the GST-mu clade. These results provide new insights into metazoan GST diversity and the biochemical mechanisms used by marine organisms to cope with their chemically defended prey.

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“…Individuals with these genotypes produce no GSTM1 and GSTT1 protein and consequently have complete lack of GSTM1 and GSTT1 enzymatic activity. It has been reported that approximately 50% and 20% of Caucasian population possess GSTM1-null and GSTT1-null genotype, respectively (Landi 2000;Eaton and Bammler 1999). GSTP1 enzyme activity may be altered due to single-nucleotide polymorphism (SNP), A to G transition, which results in substitution of amino acid isoleucine (Ile) with valine (Val) (Watson et al 1998 (Watson et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Common Polymorphisms in GSTA1, GSTM1 and GSTT1 Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia

Matić

Dragićević²,

Pekmezović

et al. 2016

Tohoku J. Exp. Med.

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Balkan endemic nephropathy (BEN) is a chronic familial form of interstitial nephritis that might eventually lead to end stage renal disease. This nephropathy affects individuals living along of the Danube River and its tributaries in Serbia, Bosnia, Croatia, Bulgaria and Romania. The increased incidence of urinary tract tumors in the BEN areas is well described, but its specific genetic predisposition is still unclear. Certain nephrocarcinogenic compounds, including those associated with BEN, are metabolized by glutathione S-transferase (GST) superfamily of phase II detoxication enzymes. Importantly, the GST-mediated detoxification may result in formation of more toxic compounds. We examined the association of common GST polymorphisms and bladder cancer (BC) risk in individuals from BEN areas in Serbia. A hospitalbased case-control study included 201 BC cases (67 from BEN region) and 122 controls. Each polymorphism was identified by a PCR-based method. Individuals from BEN region with low-expression GSTA1 genotype (AB+BB) exhibited a 2.6-fold higher BC risk compared to those with GSTA1 (AA) genotype who were from non-BEN region (OR = 2.60, p = 0.015). In contrast, carriers of GSTM1-active genotype from BEN region had a 2.9-fold increased BC risk compared to those with GSTM1-active genotype from non-BEN region (OR = 2.90, p = 0.010). Likewise, carriers with GSTT1-active genotype from BEN region exhibited 2.1-fold higher BC risk compared to those from non-BEN region with GSTT1-active genotype (OR = 2.10, p = 0.027). Thus, common polymorphisms in GSTA1, GSTM1 and GSTT1 are associated with susceptibility to BC in individuals from BEN areas of Serbia.

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Mammalian class theta GST and differential susceptibility to carcinogens: a review

Cited by 428 publications

References 201 publications

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

Transcript profiling of enzymes involved in detoxification of xenobiotics and reactive oxygen in human normal and simian virus 40 T antigen‐immortalized oral keratinocytes

Proteomic identification, cDNA cloning and enzymatic activity of glutathione S-transferases from the generalist marine gastropod, Cyphoma gibbosum

Common Polymorphisms in<i> GSTA1</i>, <i>GSTM1</i> and <i>GSTT1 </i>Are Associated with Susceptibility to Urinary Bladder Cancer in Individuals from Balkan Endemic Nephropathy Areas of Serbia

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