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)

Hepatitis C virus (HCV), a major etiologic agent of transfusion associated hepatitis, is a positive, single-stranded RNA virus and is also known to be implicated in liver cirrhosis and hepatocellular carcinoma. Nonstructural protein 5A (NS5A) of HCV contains acidic and proline-rich amino acids in its carboxy-terminal half. These structural features resemble eukaryotic transcription activators. In this report, we show that NS5A functions as a potent transcriptional activator when fused to the yeast (Saccharomyces cerevisiae) GAL4 DNA-binding domain (1-147). The potential transcriptional activator maps to the C-terminal half of NS5A in the yeast cell. Therefore, our data provides the first evidence that NS5A may modulate host cell function at the transcriptional level.
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PMID:Hepatitis C virus nonstructural protein 5A contains potential transcriptional activator domains. 938 55

The X protein (HBx) of human hepatitis B virus (HBV) is a transcriptional activator protein. The HBx protein plays an important role in viral replication in HBV infected cells and the liver diseases including hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Therefore, the repression of HBx gene expression by hammerhead ribozymes may be a good way to inhibit HBV replication and cure HBV-related liver diseases. We designed two hammerhead ribozymes, RzA and RzB, to cleave target sites at nucleotides 114 and 309 in the HBx open reading frame (ORF), respectively. In vitro, RzA and RzB cleaved HBx RNAs at their target sites up to 52 and 75%, respectively; however, the disabled ribozymes (dRzs) which have mutations in the catalytic site did not cleave the target RNAs at all. When each of the ribozymes were cotransfected into HepG2 cells with HBx expression plasmid, RzA and RzB reduced the level of HBx mRNA to 40 and 57%, respectively. The transactivation activity of HBx protein was also reduced dramatically by the ribozymes. These results suggest that the hammerhead ribozymes, RzA and RzB, can be used for the gene therapy of liver diseases caused by HBV.
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PMID:Repression of hepatitis B virus X gene expression by hammerhead ribozymes. 1020 56

Nrf2 is a basic leucine zipper transcriptional activator that is essential for the coordinate transcriptional induction of various antioxidant drug-metabolizing enzymes. Numerous studies have firmly established Nrf2's importance in protection from oxidative stress and certain chemical insults. Given the protective function of Nrf2, surprisingly few studies have focused on the relationship between Nrf2 and apoptosis. Therefore, we analysed how Nrf2 influences Fas signaling using Nrf2-deficient T cells. At a concentration of 1 microg/ml, the anti-Fas antibody induced 60% of cell death in Nrf2-deficient cultured thymocytes while, using the same treatment, only 40% of Nrf2 wild-type thymocytes died (P<0.05). Nrf2 deficiency enhances the sensitivity of Fas-mediated apoptosis in T cells. Next we examined the effect of Nrf2 deficiency during hepatocellular apoptosis in vivo. In comparison to wild-type mice, Nrf2-deficient mice displayed more severe hepatitis after induction with the anti-Fas antibody or tumor necrosis factor (TNF)-alpha. The enhanced sensitivity to anti-Fas or TNF-alpha stimulation was restored by preadministration of glutathione ethyl monoester, a compound capable of passing the cell membrane and upregulating the intracellular levels of glutathione. The results indicated that Nrf2 activity regulates the sensitivity of death signals by means of intracellular glutathione levels.
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PMID:Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels. 1468 86

The X protein (HBx) of human hepatitis B virus (HBV) is a transcriptional activator protein. The HBx protein plays an important role in viral replication in HBV infected cells and the liver diseases including hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Therefore, the repression of HBx gene expression by 10-23 DNAzymes might be a good way to inhibit HBV replication and counteract HBV-related liver diseases. We designed three 10-23 DNAzymes with different substrate-recognition domains. When each of the 10-23 DNAzymes were cotransfected into human AD293 cells with HBx-EGFP expression plasmid, they could all reduce the level of HBx mRNA as well as the HBx-EGFP protein. These results suggest that the 10-23 DNAzymes might be used for gene therapy of liver diseases caused by HBV.
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PMID:Inhibition of hepatitis B virus X gene expression by 10-23 DNAzymes. 1693 Jul 33