Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The changes of glutathione S-transferase activity were investigated using rat brain astroglioma C6 cells that were synchronized at different phases of the cell cycle. The enzyme showed two significant activity peaks at G2 and G1 phases. Furthermore, when C6 glioma cells were exposed to a culture medium supplemented with specific glutathione S-transferase inhibitors, ethacrynic acid and caffeic acid, cell growth was remarkably suppressed. These results suggest that glutathione S-transferases may be closely related to the mechanism of cell proliferation.
...
PMID:Possible involvement of glutathione S-transferases in the cell growth of C6 astroglioma cells. 333 40

We describe a case-control study to identify associations between polymorphism at the cytochrome P-450 (CYP2D6) and glutathione S-transferase (GSTT1 and GSTM1) loci and susceptibility to astrocytoma and meningioma. Accordingly, genotype frequencies in 112 astrocytoma and 50 meningioma patients were compared with frequencies in 577 controls. GSTM1 genotype frequencies in these groups were not different. Logistic regression analysis showed GSTT1 null and CYP2D6 poor metabolizer were risk factors in astrocytoma (odds ratio = 2.67 P = 0.0005 and odds ratio = 4.17 P = 0.0043, respectively) and meningioma (odds ratio = 4.52, P = 0.0001 and odds ratio = 4.90, P = 0.0132, respectively) when corrected for the other variables. No interactive effects between genotypes were identified. The data suggest polymorphism at loci encoding carcinogen-metabolizing enzymes influences susceptibility to astrocytoma and meningioma, possibly by determining effectiveness in the detoxification of environmental carcinogens.
...
PMID:Susceptibility to astrocytoma and meningioma: influence of allelism at glutathione S-transferase (GSTT1 and GSTM1) and cytochrome P-450 (CYP2D6) loci. 767 Dec 27

Protein extracted from conventional formalin-fixed and paraffin-embedded tissue sections of human gliomas was examined for immunoblot analysis using antibody against the placental form of glutathione S-transferase (GST-pi). Four benign astrocytomas, five anaplastic astrocytomas and four glioblastomas were used in this study. The preliminary study demonstrated that immunoreactivity of GST-pi was well preserved in normal brain tissue and normal term placenta fixed in acetone, formalin or buffered formalin (pH 7.4). GST-pi in gliomas fixed in formalin also had a good immunoreactivity and showed clear bands on nitrocellulose membranes processed by the method of Western blotting using anti-GST-pi antibody. The results of immunoblot analysis for GST-pi indicate that the intensity of immunoreactivity of benign astrocytoma, anaplastic astrocytoma and glioblastoma increases with the advance of malignancy of these neoplasms. Western blot analysis for GST-pi can be performed using protein extracted from formalin-fixed and paraffin-embedded tissue sections, and the immunoreactive bands can be analyzed quantitatively by densitometric scanning.
...
PMID:Immunoblot analysis of the placental form of glutathione S-transferase in protein extracted from paraffin-embedded human glioma tissue. 850 40

The expression levels of nm23-H1 have been reported to correlate with the metastatic potential of some tumours. We have treated a child with a rare case of astrocytoma with diffuse osteoblastic metastases. We therefore decided to examine the expression of the nm23 gene product in 24 gliomas in order to clarify the association of its expression with the clinical features of the disease. A polyclonal antibody against a GST/nm23-H1 fusion protein was raised in rabbits. Twenty-four specimens, including 5 recurrent gliomas and one extraneural metastasis, were obtained from 19 patients treated surgically between 1990 and 1993 in our hospital. Immunohistochemical staining was performed on paraffin sections using an avidin-biotinyl peroxidase complex method. Of the 24 astrocytic neoplasms, 3 (12.5%) specimens from one patient with diffuse bony metastases stained intensely with nm23-H1. Two specimens obtained from glioblastoma multiforme patients stained weakly. The other 19 specimens were negative for nm23-H1 expression. Little or no nm23 expression was observed in adjacent nontumourous cerebral tissues. The results suggest that high levels of nm23 expression might correlate with extraneural metastatic potential in astrocytic neoplasms.
...
PMID:Immunohistochemical analysis of the nm23 gene product (NDP kinase) expression in astrocytic neoplasms. 873 95

Increases in transforming growth factor beta1 (TGF-beta1) mRNA and biological activity in the early phase of human cytomegalovirus (CMV) infection in fibroblasts are paralleled by increased TGF-beta1-chloramphenicol acetyltransferase (CAT) reporter gene activity. To determine how CMV infection transactivates the TGF-beta1 promoter, we examined the effects of the cotransfected IE2 regulatory protein of human CMV on 5'-deleted TGF-beta1 promoter-CAT reporter genes in transient DNA transfection assays. Two upstream TGF-beta1 promoter regions each containing an Egr-1 consensus site were shown to be important for IE2-induced transactivation in a cell type that displayed greatly reduced nonspecific activity. Furthermore, transfer of an Egr-l site from between positions -125 and -98, but not point mutant versions of this site, to a heterologous promoter also conveyed IE2 responsiveness. Addition of an IE2 expression vector or use of the U373 A45 astrocytoma cell line expressing IE2 also produced synergistic stimulation of GAL4-Egr-l-mediated activation of a target promoter containing GAL4 binding sites. The 80-kDa IE2 protein present in A45 cells proved to selectively bind to glutathione S-transferase (GST)-Egr-1 beads. The results of in vitro protein binding assays also revealed that an intact in vitro-translated IE2 protein bound directly to the GST-Egr-1 fusion protein through the zinc finger domain of the Egr-1 protein and that this binding activity was abolished by deletion of parts of the zinc finger DNA-binding domain. Similarly, the Egr-1 protein was found to associate preferentially with a small region within the C-terminal half of the IE2 protein adjacent to the DNA-binding and dimerization domains that are important for both transactivation and downregulation. We conclude from these observations that IE2 may regulate transcription of the TGF-beta1 gene as well as other potential cellular targets by virtue of its ability to interact with the Egr-1 DNA-binding protein.
...
PMID:The IE2 regulatory protein of human cytomegalovirus induces expression of the human transforming growth factor beta1 gene through an Egr-1 binding site. 879 51

We describe studies to assess the influence of polymorphism in the human glutathione S-transferase GSTM3 gene on susceptibility to high grade astrocytoma. Immunohistochemical studies using a GSTM3-specific antiserum identified expression of the GSTM3 subunit in astrocytes. The relative levels of expression of GSTM1 and GSTM3 in brain cytosols were determined after resolution of these enzymes using chromatofocusing. We found no differences in the level of GSTM3 activity in individuals with GSTM1 null and those with GSTM1-positive genotypes (GSTM1 A, GSTM1 B and GSTM1 A/B). A case-control study was performed to determine if GSTM3 alone or in combination with GSTM1 or GSTT1 influenced susceptibility to high grade astrocytoma. After correction for differences in age and gender, GSTM3 AA was not significantly different in cases compared with controls. No significant interactions between GSTM3 AA and GSTM1 null were identified. The significant interaction between GSTM3 AA and GSTT1 null appeared to result from the strength of the main effect (GSTT1 null). The data show that while GSTM3 is expressed in astrocytes and contributes significantly to total GST activity in human brain, it does not appear to influence susceptibility to high grade astrocytoma. Further, unlike lung, there appears to be no relationship between the level of GSTM3 activity in brain and GSTM1 genotype.
...
PMID:Allelism at the glutathione S-transferase GSTM3 locus: interactions with GSTM1 and GSTT1 as risk factors for astrocytoma. 882 14

Gene deletion at the glutathione S-transferase mu locus (GSTM1) has previously been associated with increased risk for environmentally-induced cancers (e.g. smoking-related lung cancer). In the present study we examined the hypothesis that GSTM1 deletion is a risk factor for malignant brain tumors in adults. We compared the prevalence of the GSTM1 homozygous deletion polymorphism in 158 Caucasian adults with gliomas with 157 controls. Cases and controls were drawn from a large population-based case-control study of brain cancers in six San Francisco Bay area counties. Overall, the prevalence of the GSTM1 deletion was similar in cases (83/158; 53%) and controls (78/157; 50%). Among brain tumor cases, analysis of variance modeling indicated a significant interaction of GSTM1 genotype and gender associated with age at diagnosis (P = 0.02). This effect was due to the fact that women with GSTM1 deletion were younger on average at diagnosis than women who were GSTM1 positive (43.9 years versus 52.4 years, respectively). Age at diagnosis among men was similar for those who were GSTM1 deleted and GSTM1 positive (49.4 years and 47.2 years, respectively). The younger age at diagnosis of GSTM1 null female cases compared with GSTM1 positive cases was observed in astrocytoma as well as the higher grade tumors (e.g. glioblastoma multiforme). There was no association of GSTM1 deletion with age or gender in controls. These studies suggest that among female cases, GSTM1 deletion may be associated with earlier age at onset. Confirmation of these findings could provide important clues to gene-environment interactions in the etiology of malignant brain tumors.
...
PMID:Population-based study of glutathione S-transferase mu gene deletion in adult glioma cases and controls. 923 Feb 93

Though a developing body of data indicates polymorphism at GST genes influences cancer susceptibility, it is unclear why a genotype is associated with one cancer but not another. We believe the GST exert a critical role in normal cell house-keeping activities. GSTM1, GSTM3 and GSTT1 influence tumorigenesis because these enzymes utilise the products of UV-induced oxidative stress. Further support for the importance of these genes in the protection of skin from UV comes from studies in systemic lupus erythematosus (Ollier et al, 1996). Thus, GSTM1 null is associated with increased anti-Ro (but not anti-La) antibodies, a phenotype associated with photosensitivity. At present there is no basis for predicting which cancers will be influenced by GST polymorphisms though other studies do indicate that the GSTs are critical in the metabolism of environmental carcinogens. For example, GSTT1 null confers an increased risk of astrocytoma (Hand et al, 1996). While brain tumours are not clearly associated with environmental pollutants, N-methyl-N-nitrosourea, processed meats and occupation have been implicated. Why GSTT1 but not GSTM1 or GSTM3 influences the risk of astrocytoma is unclear. GSTM3 appears a good susceptibility candidate, as some astrocytes demonstrate strong expression (Hand et al, 1996). Susceptibility to squamous cell cancer of the larynx, a pathology associated with chronic consumption of tobacco and alcohol, is also influenced by allelism at GSTM3 (Jahnke et al, 1996). The roles of CYP2D6 and CYP1A1 are even more unclear, though the finding that systemic agents such as arsenic predispose to multiple BCC, suggests that CYP2D6-mediated hepatic detoxification of photosensitizing agents may be important. Importantly, the extent of altered risk conferred by genotypes is generally 2-3 fold and it is necessary to identify which other genes interact with the GST so that haplotypes associated with 10-20 fold increases in risk can be defined.
...
PMID:Polymorphism in glutathione S-transferase loci as a risk factor for common cancers. 944 13

1. The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the expression of several proteins displaying pro-inflammatory activities the regulation of which is associated to the transcription factor NF-kappaB, was assayed in the human astrocytoma cell line 1321N1. 2. Tumour necrosis factor-alpha (TNF-alpha) activated NF-kappaB as judged from both the appearance of kappaB-binding activity in the nuclear extracts, the degradation of IkappaB proteins in the cell lysates, and the activation of IkappaB kinases using an immunocomplex kinase assay with glutathione S-transferase (GST)-IkappaB proteins as substrates. 3. HTB up to 3 mM did not inhibit the nuclear translocation of NK-kappaB/Rel proteins as judged from electrophoretic mobility-shift assays; however, HTB inhibited the degradation of IkappaBbeta without significantly affecting the degradation of both IkappaBalpha and IkappaBepsilon. 4. In keeping with their inhibitory effect on IkappaBbeta degradation in the cell lysates, both HTB and triflusal inhibited the phosphorylation of GST-IkappaBbeta elicited by TNF-alpha, without affecting the phosphorylation of GST-IkappaBalpha. 5. The effect of both HTB and triflusal on kappaB-dependent trans-activation was studied by assaying the expression of both cyclo-oxygenase-2 (COX-2) and vascular cell adhesion molecule-1 (VCAM-1). HTB and triflusal inhibited in a dose-dependent manner the expression of COX-2 and VCAM-1 mRNA and the induction of COX-2 protein at therapeutically relevant concentrations. 6. These findings show the complexity of the biochemical mechanisms underlying the activation of NF-kappaB in the different cell types and extend the anti-inflammatory effects of HTB and triflusal to neural cells.
...
PMID:Effect of 4-trifluoromethyl derivatives of salicylate on nuclear factor kappaB-dependent transcription in human astrocytoma cells. 1115 5

Ptd(4,5)P(2) is thought to promote and organize a wide range of cellular functions, including vesicular membrane traffic and cytoskeletal dynamics, by recruiting functional protein complexes to restricted locations in cellular membranes. However, little is known about the distribution of PtdIns(4,5)P(2) in the cell at high resolution. We have used the pleckstrin homology (PH) domain of phospholipase delta(1) (PLCdelta(1)), narrowly specific for PtdIns(4,5)P(2), to map the distribution of the lipid in astrocytoma and A431 cells. We applied the glutathione S-transferase-tagged PLCdelta(1) PH domain (PLCdelta(1)PH-GST) in an on-section labelling approach which avoids transfection procedures. Here we demonstrate PtdIns(4,5)P(2) labelling in the plasma membrane, and also in intracellular membranes, including Golgi (mainly stack), endosomes and endoplasmic reticulum, as well as in electron-dense structures within the nucleus. At the plasma membrane, labelling was more concentrated over lamellipodia, but not in caveolae, which contained less than 10% of the total cell-surface labelling. A dramatic decrease in signal over labelled compartments was observed on preincubation with the cognate headgroup [Ins(1,4,5)P(3)], and plasma-membrane labelling was substantially decreased after stimulation with thrombin-receptor-activating peptide (SFLLRN in the one-letter amino acid code), a treatment which markedly diminishes PtdIns(4,5)P(2) levels. Thus we have developed a highly selective method for mapping the PtdIns(4,5)P(2) distribution within cells at high resolution, and our data provide direct evidence for this lipid at key functional locations.
...
PMID:Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C delta1. 1196 66


1 2 Next >>

---