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At least 19 recordsLinked to original sources
PubMed1989

Identification of the trans-stilbene oxide-active glutathione transferase in human mononuclear leukocytes and in liver as GST1.

A glutathione transferase from human mononuclear leukocytes with a high activity toward trans-stilbene oxide (GT-tSBO) has been studied in liver and blood from fetus and adults and in blood from neonates. Using starch gel electrophoresis, different phenotypes of GST1 have been determined, GST1 0, GST1 1, and GST1 2. As judged from activity measurements and the fact that only those individuals who express the null allele of GST1, the GST1 0, which has a low activity toward trans-stilbene oxide, it is concluded that the hepatic transferase GST1 is identical to GT-tSBO, as well as to hepatic transferase mu. In addition, it has been shown that the different genotypes of GST1 1 (GST1 1-1, GST1 1-0) and GST1 2 (GST1 2-2, GST1 2-0) can be separated by measuring the GT-tSBO activity in whole blood from the same individual. It is also demonstrated that GT-tSBO activity is much lower in fetal liver, approximately 10 times, compared with adult liver, while this activity seems to be unchanged in the blood from fetus and adults, as well as in neonates.

Adult↗
PubMed1989

A human homologue of the yeast GST1 gene codes for a GTP-binding protein and is expressed in a proliferation-dependent manner in mammalian cells.

A human homologue (GST1-Hs) of the yeast GST1 gene that encodes a new GTP-binding protein essential for the G1-to-S phase transition of the cell cycle was cloned from the cDNA library of human KB cells. The GST1-Hs cDNA contained a 1497 bp open reading frame coding for a 499 amino acid protein with mol. wt 55,754 and with the amino acid sequence homologies of 52.3 and 37.8% to the GST1 protein and polypeptide chain elongation factor EF1 alpha respectively. The regions potentially responsible for GTP binding and GTP hydrolysis were conserved in the GST1-Hs protein as well. When expressed in yeast cell, the GST1-Hs gene could complement the ts phenotype of yeast gst1 mutant. GST1-Hs and its mouse homologue were expressed in human fibroblasts and in various mouse cell types respectively, at relatively low levels in their quiescent states, and the level of those expressions increased rapidly, prior to the onset of DNA replication and the total RNA synthesis, when human or mouse fibroblasts were progressed out of the growth-arrested state by the addition of serum. A possible role of GST1-Hs in mammalian cell growth is discussed.

Amino Acid Sequence↗
PubMed2024

Loss of Gst1 enhances resistance to MMS by reprogramming the transcription of DNA damage response genes in a Rad53-dependent manner in Candida albicans.

The DNA damage response is a highly conserved protective mechanism that enables cells to cope with various lesions in the genome. Extensive studies across different eukaryotic cells have identified the crucial roles played by components required for response to DNA damage. When compared to the essential signal transducers and repair factors in the DNA damage response circuitry, the negative regulators and underlying mechanisms of this circuitry have been relatively under-examined. In this study, we investigated Gst1, a putative glutathione transferase in the fungal pathogen Candida albicans. We found that under stress caused by the DNA damage agent MMS, GST1 expression was significantly upregulated, and this upregulation was further enhanced by the loss of the checkpoint kinases and DNA repair factors. Somewhat counterintuitively, deletion of GST1 conferred increased resistance to MMS, potentially via enhancing the phosphorylation of Rad53. Furthermore, overexpression of RAD53 or deletion of GST1 resulted in upregulated transcription of DNA damage repair genes, including CAS1, RAD7, and RAD30, while repression of RAD7 transcription in the GST1 deletion reversed the strain's heightened resistance to MMS. Finally, Gst1 physically interacted with Rad53, and their interaction weakened in response to MMS-induced stress. Overall, our findings suggest a negative regulatory role for GST1 in DNA damage response in C. albicans, and position Gst1 within the Rad53-mediated signaling pathway. These findings hold significant implications for understanding the mechanisms underlying the DNA damage response in this fungal pathogen and supply new potential targets for therapeutic intervention.

Candida albicans↗
PubMed1989

Immunohistochemical localization of human liver glutathione S-transferase (GST) isozymes with special reference to polymorphic GST1.

The products of three human glutathione S-transferase (RX:glutathione R-transferase, EC 2.5.1.18) (GST) loci (GST 1, GST 2 and GST 3) were purified and their immunohistochemical localization in liver was studied with special attention to the polymorphism of GST1 (neutral isozyme). The GST1 was homogeneously stained in cytoplasm of hepatocytes throughout the lobule of liver showing GST1 1, GST1 2 and GST1 2-1 phenotypes. However, none of the hepatic tissue showing GST1 0 phenotype was stained. Immunohistochemical staining of GST2 (basic isozyme) was distributed in the cytoplasm of hepatocytes homogeneously throughout the hepatic lobule in all cases and the strong staining intensity was also demonstrated in nucleus. GST3 (acidic isozyme) was strongly stained in biliary epithelium, while staining of hepatocytes was not apparent. These results indicate that the human liver GST isozymes exhibit significant difference in their inter-individual, specific cellular and organellar distribution.

Animals↗
PubMedDate not supplied

Detection of GST1 gene deletion by the polymerase chain reaction and its possible correlation with stomach cancer in Japanese.

A homozygous gene deletion at the GST1 locus of genomic DNA isolated from peripheral blood was investigated for its relationship with several types of cancer using the polymerase chain reaction (PCR) technique. DNA samples were prepared from blood obtained from 128 healthy blood donors and 150 patients with cancer or chronic hepatitis. PCR primers were prepared based on the human cDNA sequence and the intron/exon sequences of the rat Yb2 gene. The amplified sequence between exons 5 and 6 including intron 5 showed very clearly the presence of absence of the GST1 gene, after electrophoresis in a 2% agarose gel. Segregation of the presence and absence of PCR product from samples of twins and their parents indicated that presence involves homozygous or heterozygous normal GST1 genotypes while absence involves only homozygous gene deletion. The patients with stomach cancer had a significantly higher frequency of gene deletion than did the healthy controls (P < 0.005). Thus, GST1 deletion may be a possible genetic marker for early detection of a group at high risk of stomach cancer.

Asian People↗
PubMed1992

Mapping of the human GSPT1 gene, a human homolog of the yeast GST1 gene, to chromosomal band 16p13.1.

The GSPT1 gene, a human homolog of the yeast GST1 gene (formerly named GST1-Hs), was mapped on human chromosome 16p13.1 by a combination of nonradioactive in situ hybridization and Giemsa staining. Southern blot hybridization with a panel of human-rodent somatic cells confirmed the location of the GSPT1 gene on chromosome 16 and also showed the existence of a homologous gene on the X chromosome. A breakpoint for nonrandom chromosome rearrangements has been found in the region of GSPT1 in patients with acute nonlymphocytic leukemia.

Blotting, Southern↗
PubMed1991

The human glutathione S-transferases: a case-control study of the incidence of the GST1 0 phenotype in patients with adenocarcinoma.

The suggestion that individuals with the GST1 0 phenotype have a greater susceptibility to carcinogens than those with other GST1 phenotypes has been examined by using a starch gel zymogram approach to compare the frequency of this phenotype in control subjects and a group of patients with adenocarcinoma of stomach and colon. A significantly greater proportion of the patients with adenocarcinoma demonstrated the null phenotype, odds ratio analysis indicating that individuals with this polymorphic variant have an approximately 3-fold greater risk of developing these cancers.

Adenocarcinoma↗
PubMed1991

Purification and characterization of human muscle glutathione S-transferases: evidence that glutathione S-transferase zeta corresponds to a locus distinct from GST1, GST2, and GST3.

Human muscle glutathione S-transferase isozyme, GST zeta (pI 5.2) has been purified by three different methods using immunoaffinity chromatography, DEAE cellulose chromatography, and isoelectric focusing. GST zeta prepared by any of the three methods does not recognize antibodies raised against the alpha, mu, or pi class glutathione S-transferases of human tissues. GST zeta has a blocked N-terminus and its peptide fingerprints also indicate it to be distinct from the alpha, mu, or pi class isozymes. As compared to GSTs of alpha, mu, and pi classes, GST zeta displays higher activities toward t-stilbene oxide and Leukotriene A4 methyl ester. GST zeta also expresses GSH-peroxidase activity toward hydrogen peroxide. The Kms of GST zeta for CDNB and GSH were comparable to those reported for other human GSTs but its Vmax for CDNB, 7620 mol/mol/min, was found to be considerably higher than that reported for other human GSTs. The kinetics of inhibition of GST zeta by hematin, bile acids, and other inhibitors also indicate that it was distinct from the three classes of GST isozymes. These studies suggest that GST zeta corresponds to a locus distinct from GST1, GST2, and GST3 and probably corresponds to the GST4 locus as suggested previously by Laisney et al. (1984, Human Genet. 68, 221-227). The results of peptide fingerprints and kinetic analysis indicate that as compared to the pi and alpha class isozymes, GST zeta has more structural and functional similarities with the mu class isozymes. Besides GST zeta several other GST isozymes belonging to pi and mu class have also been characterized in muscle. The pi class GST isozymes of muscle have considerable charge heterogeneity among them despite identical N-terminal sequences.

Amino Acid Sequence↗
PubMed1992

Genetic monitoring of human polymorphic cancer susceptibility genes by polymerase chain reaction: application to glutathione transferase mu.

Several genes involved in the metabolism of carcinogens have been found to be polymorphic in human populations and are associated with increased risk of cancer at some sites. This study focuses on the polymorphic enzyme glutathione transferase mu (GT mu). Smokers with low lymphocyte GT mu activity are at an approximately 2-fold higher risk for lung cancer and an approximately 3-fold higher risk for stomach and colon adenocarcinomas. Recent cloning and sequencing of the GST1 gene has allowed the development of convenient genotyping methods based on restriction fragment length polymorphisms (RFLP) or the polymerase chain reaction (PCR). The GST1 polymorphism has been shown to be a deletion of the gene locus. To detect the presence or absence of the gene we amplified exons 4-5 and/or exons 6-7 of the GST1 gene by PCR. PCR amplification produced bands of 215-bp or 273-bp from individuals with one or two copies of the GST1 allele and no band if the individual was homozygously deleted (0/0). In the exon 6-7 PCR, we co-amplified a 268-bp portion of the beta-globin gene as an internal reference standard for quantitative analysis of product yield. This allowed homozygote individuals (+/+) to be distinguished from heterozygotes (+/0). We have compared the GST1 genotype to lymphocyte GT mu activity measured on trans-stilbene oxide (TSO) in the lymphocytes of 45 individuals. Low GT mu activity (< 67 pmole/min/10(7) cells) was strongly associated (24/24) with the GST1 0/0 genotype. With the exception of one individual, activities greater than 67 pmole/min/10(7) were associated with the presence of the GST1 allele (20/21). Individuals with the highest GT-TSO activity were found to be homozygous for GST1. (+/+), while heterozygotes (+/0) generally had lower activity, suggesting a gene dosage effect in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Gene Deletion↗
PubMed1990

[Hereditary polymorphism of glutathione-S-transferase in the human liver in normal conditions and in alcoholic hepatitis].

A total of 100 autopsy liver extracts from Russian individuals were examined for glutathione-S-transferase I (GST1) isozymes by means of starch gel electrophoresis. The gene frequencies of GST1* 1, GST1* 2 and GST1* 0 were 0.051, 0.251 and 0.697, respectively. Analysis of data obtained and those in literature for other populations revealed the difference between European and Mongoloid groups. The GST1 0 phenotype was found in samples of liver from individuals with alcoholic hepatitis at frequency 77.3%. The gene frequencies for GST1* 1, GST1* 2 and GST1* 0 were 0.020, 0.100 and 0.879, respectively.

Glutathione Transferase↗
PubMed1989

Glutathione-S-transferase (GST) polymorphism among ethnic groups in Singapore with report of additional alleles at loci 1 and 2.

Glutathione S-transferases (GST; E.C.2.5.1.18) were phenotyped by starch gel electrophoresis in post-mortem liver samples from 683 unrelated subjects of both sexes. 305 were Chinese, 185 Indians, 147 Malays and 46 from other racial groups of South-East Asia. GST1 and GST2 were found to be polymorphic in these populations. Additional alleles (GST1*3 and GST2*O) were observed at low frequency in all the ethnic groups. The frequency of GST1*1 was lower and that of GST1*2 was higher in Indians and Malays as compared to Chinese. GST1*0 and GST1*3 frequencies were similar in all these ethnic groups. The gene frequencies of the alleles of the GST2 locus varied significantly in the population studied. GST2*0 frequency was significantly higher in Indians than in Chinese and Malays, while the lowest frequency of GST2*1 was found in the Indians. GST2*2 frequency was higher in the Malays than in Chinese and Indians. GST1 and GST2 phenotype distributions were in agreement with Hardy-Weinberg equilibrium in all the ethnic groups studied. Sex made no significant difference in the phenotype distribution.

Alleles↗
PubMed1989

[Immunochemical properties and immunohistological localization of human liver glutathione S-transferase isozymes].

The products of three human glutathione S-transferase (GST) loci (GST1, GST2 and GST3) were purified and their immunochemical properties as well as immunohistological localization in liver were studied. Three group of isozymes were different in molecular weight, substrate specificities and antigenicity. Two homodimers (type 1 and type 2) of GST1 which shows genetic polymorphism, were similar in immunochemical properties other than isoelectric point. Inactivity of GST1 0 was due to impaired protein synthesis. Immunohistologically, GST1 isozyme was homogeneously stained in cytoplasm of hepatocytes throught the lobule of liver showing GST1 1, GST1 2 and GST1 2-1 phenotypes. On the other hand, GST2 isozyme was stained in the cytoplasm as well as the nucleus of hepatocytes throughout the hepatic lobule in all cases. GST3 isozyme was strongly stained in biliary epithelium. These results indicate that the human liver GSTs are composed of three immunochemically distinct isozymes, which exhibit significant difference in inter-individual, specific cellular and organellar distribution.

Glutathione Transferase↗
PubMed1992

The human glutathione S-transferases: comparison of isoenzyme expression in normal and astrocytoma brain.

We describe expression of alpha, mu and pi class glutathione S-transferases (GST) in brain tissue from 21 controls and uninfiltrated and tumour tissue from 17 glioma patients. GST were sequentially resolved by chromatofocusing into the GST2, GST1, GST5, GST2 (5.5), GST3, GST6 sets and the contribution of each to total activity determined. The immunological identity of these isoforms was studied using immunoblotting. The pi class GST3 isoform was the major contributor to activity in control tissue (70.9%) and, uninfiltrated (75.1%) and tumour samples (82.4%). Expression was significantly greater in the tumours (P less than 0.05). Expression of alpha isoforms GST2 and GST2 (5.5) was variable with most subjects demonstrating no detectable GST2 (B1 and B2 chromatofocused monomers). An isoform termed GST2 (5.5) chromatofocussed at pH 5.5 and cross-reacted with antisera to B1. It was detected in most control and glioma patients and comprised about 5% of total activity. The contribution of GST2 and GST2 (5.5) to activity was similar in control, uninfiltrated and tumour tissue. Two mu class enzymes, GST1 and GST5, were identified. GST1 isoforms were detected in 9 of 21 control samples, the phenotype of these and matched liver samples were identical. GST1 isoforms were detected in 4 of 16 tumour samples, a significantly lower incidence than in a previously established control group. GST5 was expressed in most samples, the contribution of this locus to activity was significantly reduced in the tumours (5.2%) compared with control samples (14.5%).

Astrocytoma↗
PubMed1992

Insect glutathione S-transferases. Biochemical characteristics of the major forms from houseflies susceptible and resistant to insecticides.

Two classes of glutathione transferases have been identified and purified from Musca domestica. The first, designated as GST1, migrates as a single band of 28 kDa in SDS-gel electrophoresis, and the second, designated as GST2, migrates as a 32-kDa band. Antisera prepared against each class have no immunological cross-reactivity, and heterodimeric associations between the two classes have not been detected. Each class is composed of several isoforms: GST1 is composed of forms with isoelectric points from 4 to 9, whereas all the forms of GST2 have acidic pI values. Screening of cDNA libraries yielded clones coding for GST1, and the gene was sequenced and expressed in Escherichia coli. The high activity found in an insecticide-resistant strain (Cornell R) is correlated with high level of GST1 transcript.

Amino Acid Sequence↗
PubMed1988

A yeast gene required for the G1-to-S transition encodes a protein containing an A-kinase target site and GTPase domain.

A new temperature-sensitive mutant of Saccharomyces cerevisiae, gst1 (G1-to-S transition) was isolated. At nonpermissive temperature the mutant cells with large buds accumulated and DNA synthesis was substantially arrested. From the reciprocal experiment of temperature-shift and mating-factor treatment, it was shown that the execution point was post 'START'. This suggested that the mutation affected the G1-to-S phase transition in the cell cycle. A DNA clone complementing the gst1-1 mutation was isolated from a yeast gene library, and gst1 was mapped in chr4R, by Southern blotting of cloned sequence to the individual yeast chromosome DNA by OFAGE system and by genetic analysis. The gene product was tentatively assigned from DNA sequencing analysis, as a protein of mol. wt 76,565 which contained consensus sequences for a target site of cAMP-dependent protein kinase(s) and for GTPase with extensive homology to polypeptide chain elongation factor EF1 alpha.

Amino Acid Sequence↗
PubMed1989

The development expression of alpha-, mu- and pi-class glutathione S-transferases in human liver.

The developmental expression of the alpha, mu and pi class glutathione S-transferases has been defined in human liver using radioimmunoassay and immunohistochemistry. Expression of alpha and mu class isoenzymes increased significantly at birth, while that of the pi isoenzyme declined during the first trimester. Mu-class isoenzymes (GST1 1, GST1 2, GST1 2-1) were expressed in hepatocytes but not in other liver cell types.

Aging↗
PubMed1991

[Distribution of glutathione S-transferase isozymes in rat small intestinal mucosa].

We have investigated the longitudinal distribution of glutathione S-transferase (GST) isozymes in the trisected small intestine mucosa of rats. Only GST subunits 1 and 7 were detected by Western blot analysis of the intestinal cytosol using antiserum for GST1-1, 1-2, 3-4 and 7-7. Cytosolic GST1-1, 3-4 and 7-7 were assayed by the quantitative ELISA. There was a marked decline of the concentration of GST1-1 from proximal (35.17 nmol/g tissue) to distal intestine (1.67 nmol/g tissue). GST3-4 was hardly detected in the intestinal mucosa. Among the GSTs, GST7-7 existed in the highest concentration in any segment of intestine, i.e. 58.76 nmol/g tissue (61% of GSTs) in the proximal intestine and 32.38 nmol/g tissue (93% of GSTs) in the distal intestine.

Animals↗