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

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

Glutathione S-transferase (GST; EC 2.5.1.18), a sensitive marker of hepatocellular damage, was measured in patients on therapy for histologically proven, autoimmune chronic active hepatitis at various stages of the disease. GST levels were elevated in 65% of serum samples despite immuno-suppressive treatment compared with aspartate transaminase (AST) which was increased in only 23% of samples. In 55% of samples with normal AST concentrations, GST was elevated. No samples demonstrated abnormal transaminase with normal GST levels. It is concluded that continuing hepatocellular damage occurs in patients with autoimmune chronic active hepatitis on immuno-suppressive treatment.
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PMID:Glutathione S-transferase levels in autoimmune chronic active hepatitis: a more sensitive index of hepatocellular damage than aspartate transaminase. 337 Aug 35

Thirty-six wild-caught woodchucks (Marmota monax) were characterized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens [i.e., a tryptophan pyrolysate product, aflatoxin B1, 2-aminofluorene, and trans-7,8-dihydrobenzo(a)pyrene] to mutagenic metabolites in the Ames reversion test and to decrease the activity of direct-acting mutagens [i.e., 4-nitroquinoline N-oxide, 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine X 2HCl, and sodium dichromate]. A considerable interindividual variability in metabolism was observed among the examined woodchucks. Some of the investigated parameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reductase and NADPH-dependent diaphorase) were statistically significant. The comparison of the monitored activities in woodchucks and in other rodent species (rat and mouse) led to the conclusion that the liver metabolism of mutagens and carcinogens in woodchucks is more oriented in the sense of activation, while detoxification mechanisms are more efficient in rats and mice.
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PMID:Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection. 360 50

The nuclear lamina of mammalian cells consists of three major proteins, lamins A, C, and B, and a fourth minor protein, lamin B2. Lamins belong to the family of intermediate filaments and are highly similar both in structure and primary sequence. They are organized in three well-defined domains: 1) a central alpha-helical rod, which is a secondary structure shared by all types of intermediate filaments, formed by three alpha-helices (coils 1A, 1B, and 2) and surrounded by 2) an amino-terminal head and 3) a carboxyl-terminal tail. Autoantibodies toward major lamin have been described previously in sera from patients with different autoimmune diseases. We chose an epitope mapping approach to further characterize the autoimmune response to nuclear lamin. Different lamin B2 domains were expressed as fusion proteins with the glutathione S-transferase and then used in immunoblotting experiments to analyze sera from patients with autoimmune diseases (chronic active hepatitis, SLE, rheumatoid arthritis, and polymyalgia rheumatica) and from healthy subjects. At a 1:1000 dilution, none of the control sera recognized any of the recombinant polypeptides. Conversely, reactive sera were present in all groups of patients. The ability to recognize a protein domain seemed to differ with the pathology. Most chronic active hepatitis sera were reactive to two or more lamin domains and reacting SLE sera always gave positive signals to coil 2 and/or coil 1B. Coil 2 was preferentially recognized by rheumatoid arthritis sera. Polymyalgia rheumatica sera differed from all of the others because of their low reactivity to the rod domain and preference for the C terminus, a lamin-specific domain.
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PMID:Autoantibodies to human nuclear lamin B2 protein. Epitope specificity in different autoimmune diseases. 751 47

Balb/c mice were immunized with basic glutathione s-transferase (B-GST) prepared from human liver and the monoclonal antibody against B-GST was purified. Serum B-GST level was measured in 234 patients with various types of viral hepatitis with solid radioimmuno-sandwich assay and the value in 70 donors (4.19 +/- 4.42 ng/ml) used as control. The serum B-GST level in 117 cases with acute icteric hepatitis, 85 cases with chronic active hepatitis and 32 cases with severe hepatitis were 8.6, 8.4 and 5.9 times higher than that of the controls respectively. At the same time, serum alanine amino-transferase (ALT) activity in patients with various types of viral hepatitis were 6.8, 3.1 and 2.4 times higher respectively. These results showed that the change of serum B-GST level was more prominent than that of ALT activity. In addition, the change of B-GST in 35 patients with CAH and 13 with severe hepatitis were serially observed. Serum B-GST level persisted at high level for a long time in most of the patients, while serum ALT activity soon became normal. It is shown that serum B-GST level is more valuable than ALT in estimating chronic and severe liver damage.
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PMID:[Preparation of monoclonal antibody against basic glutathione S-transferase and its clinical application]. 815 52

It is shown that chronic hepatobiliary pathology is associated with a fall in spontaneous metabolite conjugation related to reduced concentration of hepatic glutathione. There was also enhanced activity of glutathione-dependent enzymes. This indicates progress of compensatory processes associated with mobilization of detoxication phase 2, i.e. stimulation of conjugation processes under depression of cytochrome P-450 system. The authors ascertain high informative value of hepatic glutathione transferase in assessment of disease activity in patients with chronic active hepatitis and hepatic cirrhosis.
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PMID:[The clinical significance of the liver glutathione system in chronic lesions]. 917 70

Mice naturally infected by Helicobacter hepaticus develop a chronic active hepatitis leading to hepatocellular carcinoma. This mouse model of liver cancer was used to examine the impact of bacterial infection on the hepatic expression and activity of enzymes involved in carcinogen bioactivation (phase I enzymes) and detoxification (phase II enzymes). No major differences in total cytochrome P450 (CYP) content were found between control and infected mice during the course of the study. The most striking modulations of individual isoenzymes were the increases in immunohistochemical staining observed for CYP1A and CYP2A5 in relation to increasing age and liver lesions. The increase in CYP2A5 in mice aged over 12 months was confirmed by the observed increases in coumarin 7-hydroxylation (CYP2A5 substrate) in vitro and CYP2A5 mRNA levels by Northern blot analysis. Immunoblotting confirmed the specific induction of CYP1A2 in infected mice 12 and 18 months of age. Perfusion of liver with nitroblue tetrazolium, an indicator for superoxide formation, demonstrated that in livers of infected mice, hepatocytes often co-expressed CYP2A5 and formazan deposition. Concerning phase II enzymes, an enhancement of glutathione S-transferase (GST) activities, related to the disease process, was observed in infected mice. An age-specific increase of GSTpi and A4.4 (early stage of disease) and GST YaYa (>9 months) expression was also demonstrated by immunohistochemical staining. In contrast, catalase and glutathione-peroxidase activities, as well as reduced glutathione content were decreased in the early stages of disease (3-9 months) in infected mice compared to age-matched control mice. Overall, these results suggest that alterations in CYP and GST expression may contribute to the aetiology of tumour incidence due to H. hepaticus infection via production of reactive oxygen species.
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PMID:Distinct time courses of increase in cytochromes P450 1A2, 2A5 and glutathione S-transferases during the progressive hepatitis associated with Helicobacter hepaticus. 939 19

The nonenzymatic conjugation of metabolites is decreased in chronic diseases of the liver, which is caused by decreased concentration of glutathione. The activities of glutathione enzymes are increased, this indicating the development of compensatory processes of mobilization of the second phase of detoxication, that is, increased conjugation under conditions of suppression of the cytochrome P-450 system. Measurement of liver glutathione transferase is a highly informative test for assessing the activity of the pathological process, particularly important in patients with chronic active hepatitis and cirrhosis of the liver.
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PMID:[Activities of glutathione enzymes in liver biopsy specimens in chronic lesions of hepatocytes]. 962 74

Helicobacter hepaticus is a bacterial pathogen that causes chronic active hepatitis and inflammatory bowel disease in mice. The purpose of this study was to develop a recombinant antigen-based enzyme-linked immunosorbent assay (ELISA) to detect H. hepaticus-infected mice. A genomic library of H. hepaticus was constructed and was screened with sera from H. hepaticus-infected mice. A 459-bp open reading frame that coded for an 18-kDa immunoreactive protein, MAP18, was identified. The gene had high identity with genes coding for outer membrane proteins of other bacteria, and the predicted amino acid sequence of MAP18 had a putative membrane-trafficking signal sequence and a putative signal peptidase II cleavage site. The recombinant protein was expressed in Escherichia coli as a glutathione S-transferase (GST) fusion protein, GST-MAP18, and purified by affinity chromatography. The 44-kDa fusion protein was detected on Western blots probed with sera from H. hepaticus-infected mice but was not detected on blots probed with sera from mice infected with Helicobacter muridarum or Helicobacter bilis or with sera from mice free of Helicobacter infection. The GST-MAP18 fusion protein was used as an antigen in an ELISA to detect anti-H. hepaticus antibodies in sera from infected mice. This ELISA was compared to an H. hepaticus-specific ELISA that uses a detergent extract of H. hepaticus as the antigen. Sera from mice naturally and experimentally infected with H. hepaticus, H. bilis, or H. muridarum and sera from mice free of Helicobacter infection were evaluated. Both ELISAs performed with a high specificity (98%); however, the detergent extract-based ELISA performed with a higher sensitivity (89%) than the recombinant protein-based ELISA (sensitivity, 66%). These data indicate that H. hepaticus carries a gene that encodes an immunogenic 18-kDa membrane-associated protein; however, antibodies to this protein are not detected in all infected mice.
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PMID:Cloning and expression of an immunogenic membrane-associated protein of Helicobacter hepaticus for use in an enzyme-linked immunosorbent assay. 1047 29

In experimental studies, bovine lactoferrin (bLF) has been found to significantly inhibit colon, esophagus, lung, and bladder carcinogenesis in rats when administered orally in the post-initiation stage. Furthermore, concomitant administration with carcinogens resulted in inhibition of colon carcinogenesis, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 (CYP1A2), which is preferentially induced by carcinogenic heterocyclic amines. Enhancement of the activities of their phase II counterparts, such as glutathione S-transferase might have also played a critical role in post-initiation suppression in a study of tongue carcinogenesis. Anti-metastatic effects were moreover detected when bLF was given intragastrically to mice bearing highly metastatic colon carcinoma 26 cells (Co 26Lu), with apparent enhancing influence on local and systemic immunity. Marked increase in the number of cytotoxic T and NK cells in the mucosal layer of the small intestine and peripheral blood cells was thus found, this in turn enhancing the production of Interleukin 18 (IL-18) and caspase-1 in the epithelial cells of the small intestine, with possible consequent induction of interferon (IFN)-gamma positive cells. Furthermore, bLF has been found to exert anti-hepatitis C virus (HCV) activity in a preliminary clinical trial in patients with chronic active hepatitis due to this virus, a main causative factor in hepatocellular carcinoma development in Japanese. More extensive clinical trials are now underway in the National Cancer Center Hospital and other institutes to further explore the preventive potential against colon carcinogenesis.
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PMID:Cancer prevention by bovine lactoferrin and underlying mechanisms--a review of experimental and clinical studies. 1190 37

The glutathione S-transferase (GST) supergene family is made up of four gene families responsible for the biotransformation of drugs and other xenobiotics. Genetic variations in this supergene family influence individual detoxification levels and may contribute to the development of cancer. A hospital-based case-control study was conducted to evaluate the association between GST polymorphism among Filipino patients positive for hepatitis B virus (HBV DNA) and clinically diagnosed as either with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma as well as normal individuals negative for HBV infection. Multiplex PCR was used to detect the presence or absence of the GSTT1 and GSTM1 polymorphisms in peripheral blood. DNA sequencing of the S gene region of the virus was used to determine the predominant genotype found among HBV-infected patients. Our results showed that the odds of having a chronic liver disease is only 0.95 (95% CI 0.58-1.57) among those with GSTT1 null genotype compared to those with GSTT1+ genotype. On the other hand, the odds of chronic liver disease is 17.85 times (95% CI 7.34-43.45) for those with GSTM1 null genotype compared to those with GSTM1+ genotype. Using the GSTT1+/GSTM1+ genotype as the reference, both GSTT1+/GSTM1- (OR 16.61; 95% CI 6.69-41.22) and GSTT1-/GSTM1- (OR 11.91; 95% CI 4.48-31.66) genotypes seem to be risk factors for chronic liver disease. From our observations, we conclude that polymorphism in GSTM1 null genotype (OR 17.85; 95% CI 7.34-43.45) seem to be associated with an increased risk of chronic liver disease among Filipinos.
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PMID:Association of glutathione S-transferase T1 and M1 genotypes with chronic liver diseases among Filipinos. 2272 52


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