Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Marked alterations of hepatic drug-metabolizing enzymes were observed in hepatitis- and hepatoma-predisposed rats (LEC rats) fed a choline-deficient diet. The diet enhanced the development of hepatitis with severe jaundice. The levels of two major classes of cytochrome P-450, P-450PB and P-450MC, were markedly decreased. GST-Yp was dramatically increased, whereas GST-Ya, Yb1 and Yb2 were decreased. LEA rats (the control rats to LEC) fed a choline-deficient diet mimicked LEC rats fed a normal diet in terms of the above enzyme alterations, indicating that hypomethylation is involved in the pathogenesis of hepatitis and hepatoma in LEC rats. Such hypomethylation may initiate the hepatocytes that spontaneously develop hepatitis and hepatoma.
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PMID:Enhancing effect of a choline-deficient diet on alterations of hepatic drug-metabolizing enzymes in hepatitis- and hepatoma-predisposed rats (LEC rats). 190 19

Liver tissues of LEC rats, which develop fulminant hepatitis and hepatocellular carcinoma (hepatoma), were examined by Northern blot analysis using a cDNA probe of rat placental glutathione S-transferase (GST-P). GST-P gene expression was observed not only during hepatocarcinogenesis but also in fulminant hepatitis before development of chronic hepatitis and hepatoma in LEC rats. Cholangiofibrosis in LEC rats also showed high GST-P expression. A transplantable cell line derived from spontaneous LEC hepatoma exhibited a remarkably high expression. By contrast, very weak expression was observed in the livers of young LEC rats before development of hepatitis and control strain rats. Thus, spontaneous hepatic lesions in LEC rats may provide a new clue to elucidate the mechanism of GST-P gene expression.
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PMID:Gene expression of placental glutathione S-transferase in hereditary hepatitis and spontaneous hepatocarcinogenesis of LEC strain rats. 248 61

Spontaneous occurrence of placental glutathione S-transferase (GST-P)-positive foci was observed in the livers of 5-month-old LEC rats. Quantitative studies revealed that GST-P foci appeared after the onset of hepatitis. The number and size of GST-P foci increased with age and more foci were induced in males than in females. No sex difference, however, was found in the incidence of hepatitis. Although hepatitis is necessary for the induction of GST-P foci, it is insufficient for their further growth. Since hereditary hepatitis first appears at around 4 months of age, leading to a high incidence of hepatocellular carcinomas in later life, the spontaneous occurrence of the foci may be related to the development of hepatocellular carcinoma.
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PMID:Spontaneous occurrence of placental glutathione S-transferase-positive foci in the livers of LEC rats. 289 58

alpha-Glutathione S-transferase (alpha-GST; EC 2.5.1.18) has been advocated as a better marker of hepatocellular damage than the transaminases in toxic and autoimmune hepatitis. We have assessed the potential interest of plasma alpha-GST determination in 94 anti-hepatitis C virus-positive patients with histologically proven chronic hepatitis C (34 women, 60 men, ages 40.0 +/- 11.9 years). Blood samples were assayed for aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, alkaline phosphatase, and alpha-GST on the same day a liver biopsy was performed. alpha-GST concentrations were significantly above reference values in 64% of patients (compared with 58% for AST, 68% for ALT), and this increase was seen in 52% of patients with normal values for transaminases and a Knodell score > 3. Furthermore, there was a significant correlation between alpha-GST and lobular necrosis score (r = 0.31; P < 0.01). Our findings suggest that association of plasma alpha-GST with ALT may improve the biochemical assessment of liver damage in patients with chronic hepatitis C.
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PMID:Plasma alpha-glutathione S-transferase assessed as a marker of liver damage in patients with chronic hepatitis C. 749 11

Hepatitis delta virus (HDV) encodes two proteins, the small hepatitis delta antigen (SHDAg) and large hepatitis delta antigen (LHDAg). Both proteins are identical except for the presence of additional 19 amino acids at the C terminus of LHDAg. While SHDAg is required for HDV RNA replication, LHDAg inhibits replication and is required together with hepatitis B surface antigen for the assembly of HDV. The C-terminal last 4 amino acids of LHDAg (Cys-Arg-Pro-Gln) is an isoprenylation motif. It has previously been shown that the mutation of the Cys inhibited the assembly of HDV. In order to discern whether this effect is due to change of amino acid residue or abolition of isoprenylation, we constructed several LHDAg mutants of the terminal three amino acid residues and tested their abilities to be packaged with HBsAg by cotransfection experiments. We also made GST-fusion proteins of these mutants and tested their abilities to be isoprenylated in rabbit reticulocyte lysate system. We found that some, but not all, of the substitutions of the amino acid residues other than the Cys also inhibited isoprenylation and that the status of isoprenylation of these mutant proteins correlated well with their abilities to be packaged with HBsAg into virions. This result indicates that isoprenylation, rather than the primary amino acid sequence, is required for LHDAg packaging. Furthermore, we found that the attachment of an isoprenylation motif to SHDAg did not enable it to be packaged with HBsAg and that the deletions of any 5 amino acids in the last 15 amino acids (amino acids 196 to 210) unique to the LHDAg abolished the packaging ability. In contrast, the deletion of 33 amino acids (amino acids 163 to 195) upstream of the last C-terminal 19 amino acids of LHDAg did not interfere with its packaging ability. Therefore, we conclude that the 15 amino acids upstream of the isoprenylation site of LHDAg are also essential for HDV assembly, and a large portion of the alleged C-terminal Pro/Gly-rich region (amino acids 146 to 195) is not required for the assembly process.
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PMID:Isoprenylation of large hepatitis delta antigen is necessary but not sufficient for hepatitis delta virus assembly. 811 40

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

The hepatitis delta virus large antigen (lHDAg) is a virally encoded protein that contains a prenylation signal sequence at its carboxyl terminus consisting of the tetrapeptide Cys-Arg-Pro-Gln. Although the presence of the Gln as the COOH-terminal residue generally specifies addition of the 15-carbon farnesyl isoprenoid, earlier reports had suggested that the protein is modified by the 20-carbon geranylgeranyl. The prenylation of lHDAg was examined in vitro using a fusion protein between glutathione S-transferase and the COOH-terminal 117 amino acids of lHDAg (GST-lHDAg). When recombinant GST-lHDAg was incubated with bovine brain cytosol in the presence of either farnesyl diphosphate or geranylgeranyl diphosphate, GST-lHDAg was preferentially farnesylated. Geranylgeranylation of the fusion protein was also observed, although at a rate considerably less than that of farnesylation. Using purified recombinant protein prenyltransferases, GST-lHDAg was found to be an excellent substrate (apparent Km = 0.8 microM) for protein farnesyltransferase (FTase), while modification by protein geranylgeranyltransferase I (GGTase I) was not detected. FTase was also able to catalyze geranylgeranylation of GST-lHDAg at a very low rate, suggesting that the low level of geranylgeranylation of GST-lHDAg observed in cytosolic preparations was mediated by FTase. Consistent with our observations on the in vitro prenylation of the GST-lHDAg fusion protein, isoprenoid analysis of authentic lHDAg expressed in COS cells demonstrated that the protein was farnesylated. Geranylgeranylation of lHDAg expressed in COS cells was not observed. As prenylation of lHDAg is required for the assembly of the hepatitis delta viral particle, these results suggest that inhibitors of FTase may be useful therapeutic agents for treatment of delta virus infection.
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PMID:The hepatitis delta virus large antigen is farnesylated both in vitro and in animal cells. 861 11

The objective of this work is to examine the possible modulation of carcinogen metabolism (activation by cytochrome P450s and detoxification by conjugation via glutathione S-transferases [GST]) in relation to hepatitis B virus (HBV)-associated liver injury. In HBV transgenic mouse lineage 107.5, the hepatitis B surface antigen (HBsAg) is expressed at noncytopathic concentrations but after injection of an HBsAg-specific, major histocompatibility complex (MHC) class I restricted cytotoxic T-lymphocyte (CTL) clone, the mice develop a severe acute necroinflammatory liver disease that reaches maximum severity within 3 days and gradually subsides during the next 2 to 3 weeks. In this model, using immunohistochemical analysis, we observed an increase of P450s (CYP1A and 2A5), both involved in aflatoxin B1, metabolism, but minor changes or no changes for others (2B, 2C, 2E, 3A). There was a fivefold decrease in the total liver P450 microsomal content 3 days' post-CTL injection with the result that the relative proportion of CYP2A5 and 1A compared with other P450s is increased. Individual microsomal P450 enzyme contents estimated by Western blotting; Northern blot analysis of liver CYP messenger RNA (mRNA) levels as well as in vitro metabolism of specific substrates for different P450 isoenzymes were consistent with the immunohistochemical data. Immunohistochemical staining with antibodies to cytosolic pi class GST was increased 1 and 3 days postinjection followed by a progressive decrease at later time points (the same phenomenon was observed to a lesser extent for GST alpha). The activity of hepatic cytosols toward substrates specific for different subclasses of GST (mu, pi, alpha) showed that while GST mu was not changed in the CTL-injected HBV transgenic mice, GST pi and, to a lesser extent, alpha were increased as compared with controls. These results suggest that liver cell injury induced by a process of acute fulminant-like hepatitis can lead to the induction of some carcinogen metabolizing enzymes notably, Cyp 1A, 2A5 and GST pi in the mouse.
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PMID:Differential induction of carcinogen metabolizing enzymes in a transgenic mouse model of fulminant hepatitis. 878 38

Recently we identified human liver endonexin II (EII) as a specific hepatitis B surface antigen (HBsAg) binding protein. To investigate whether EII is also able to interact with the HBsAg envelope of the hepatitis delta virus (H delta V), immunoprecipitation experiments were performed. H delta V particles could be co-precipitated by polyclonal rabbit anti-EII, but not by rabbit anti-glutathiontransferase (GST pi) antibodies from an H delta V-enriched fraction containing EII or GST pi. These findings suggest that H delta V particles were co-precipitated by anti-EII as a consequence of the binding between HBsAg present in the H delta V envelope and EII. Furthermore, binding of H delta V particles to human hepatocytes could be inhibited by incubation of the liver cells with rabbit anti-EII IgG or the H delta V particles with anti-idiotypic (anti-HBsAg) antibodies, developed spontaneously in rabbits immunized with EII. These findings support the assumption that small HBsAg present in the H delta V envelope is important for the attachment to the hepatocytes and that EII plays an important role in this process.
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PMID:Hepatitis delta virus attaches to human hepatocytes via human liver endonexin II, a specific HBsAg binding protein. 879 May 57

AIM:To isolate mouse CCR5 cDNA (muCCR5) and study its expression in vivo.METHODS: Marathon PCR was used to isolate muCCR5 cDNA and two animal models were designed to investigate the gene expression in vivo, one was mouse fulminant hepatitis induced by Propionibacterium acnes (P.acnes) and the other was that with delayed type hypersensitivity reaction (DTH). A specific GST-NH2-terminus of muCCR5 fusion protein antibody F(ab')(2) was prepared and clarified. RT-PCR and immunohistochemical analysis were used to observe the expression level of CCR5 gene in mice.RESULTS: A positive reaction of mouse macrophage was found in DTH but not expressed in P.acnes induced fulminant hepatitis by RT-PCR and immunohistochemical analysis.CONCLUSION: This muCCR5 expression may be involved in an allergic processmediated by cellular immunity but not acute inflammatory reaction induced by P.acnes.
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PMID:CCR5 gene expression in fulminant hepatitis and DTH in mice. 1181 19


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