Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of cyanocobalamin (CNCbl, vitamin B12) on hepatitis C virus internal ribosome entry site (HCV IRES)-dependent initiation of translation was studied by ribosomal toeprinting and sucrose gradient centrifugation analysis. These results suggested that CNCbl did not inhibit HCV IRES-dependent translation by a competitive binding mechanism. CNCbl allowed 80 S elongation complex formation on the mRNA, but stalled the initiation at that point, effectively trapping the 80 S ribosomal complexes on the HCV IRES. CNCbl had no effect on cap-dependent mRNA, consistent with the known mRNA specificity of this translational inhibitor. To help elucidate the mechanism, comparative data were collected for the well-characterised translation inhibitors cycloheximide and 5'-guanylyl-imidophosphate. Although CNCbl stalled HCV IRES-dependent translation at approximately the same step in initiation as cycloheximide, the mechanisms of these two inhibitors are distinct.
J Mol Biol 2002 May 24
PMID:Vitamin B12 stalls the 80 S ribosomal complex on the hepatitis C internal ribosome entry site. 1205 31

Chronic infections with hepatitis B (HBV) and hepatitis C (HCV) viruses are major risk factors for hepatocellular carcinoma (HCC). We have utilized a proteomic approach to determine whether a distinct repertoire of autoantibodies can be identified in HCC. Sera from 37 patients with HCC and 31 subjects chronically infected with HBV or HCV without HCC were investigated. Sera from 116 patients with other cancers, three patients with systemic lupus erythematosus, and 24 healthy subjects were utilized as controls. We report the identification of eight proteins, for each of which autoantibodies were detected in sera from more than 10% of patients with HCC but not in sera from healthy individuals (p < 0.05). Autoantibodies to four of these proteins were detected at a comparable frequency in sera from patients with chronic hepatitis. The other four proteins, which consisted of calreticulin isoforms, cytokeratin 8, nucleoside diphosphate kinase A, and F(1)-ATP synthase beta-subunit, induced autoantibodies among patients with HCC, independently of their HBV/HCV status. Calreticulin, and a novel truncated form of calreticulin (Crt32) we have identified, most commonly elicited autoantibodies among patients with HCC (27%). We conclude that a distinct repertoire of autoantibodies is associated with HCC that may have utility in early diagnosis of HCC among high risk subjects with chronic hepatitis.
Mol Cell Proteomics 2002 Mar
PMID:A distinct repertoire of autoantibodies in hepatocellular carcinoma identified by proteomic analysis. 1209 19

Remarkable progress has been made in transfusion safety from infection over the past three decades. Donor deferrals for at-risk behaviors, the introduction of more-sensitive viral-screening assays and the recent introduction of nucleic-acid amplification technology have nearly eliminated transmission of HIV and hepatitis C virus (HCV) by blood transfusion in North America. Nevertheless, risks of other infectious agents for which such robust screening tools have not been developed, such as bacteria and parasites, still remain. As a result of these successes, the non-infectious risks such as misidentification of patients and inadequate and inappropriate transfusion have become the primary sources of transfusion risk.
Trends Mol Med 2002 Jul
PMID:Blood-bank testing for infectious diseases: how safe is blood transfusion? 1211 17

The p38 mitogen activated kinase (MAPK) signaling pathway plays an essential role in regulating many cellular processes, including inflammation, cell differentiation, and cell death. Here, we report that the hepatitis C virus (HCV) core inhibits the Fas-mediated p38 signaling pathway. The Fas-mediated p38 activation is suppressed in core-expressing HepG2 cell lines, as well as in the hepatocytes of transgenic mice. In addition, core protein blocked the Fas-mediated activation of apoptosis signal-regulating kinase 1 (ASK1), a major upstream MAPKKK of p38. Treatment of a specific p38 inhibitor (SB203580) or overexpression of a kinase-defective mutant, ASK1 (K709R), promoted Fas-mediated cell death in HepG2 cells. This suggests that the p38 and ASK1 activation is required for cell survival against Fas-mediated cell death. In addition, we observed that the HCV core protein enhances Fas-mediated liver injury and lethality in transgenic mice. Collectively, our findings suggest that the HCV core inhibits the Fas-mediated p38 signaling pathway, which results in accelerated Fas-mediated cell death.
Mol Cells 2002 Jun 30
PMID:Hepatitis C virus core inhibits the Fas-mediated p38 mitogen activated kinase signaling pathway in hepatocytes. 1213 86

The hepatitis C viruses (HCVs) are a group of small enveloped RNA viruses that have been viewed as a leading cause of chronic hepatitis in humans. Infections by HCV represent a serious global health problem, because millions of people worldwide are infected and no efficient treatment is available at the present time. Since HCV was identified in 1989, considerable effort has been devoted to the discovery and development of novel molecules to treat HCV-related diseases. One of the approaches is the development of novel inhibitors that interrupt the normal functions of HCV NS5B, an RNA-dependent RNA polymerase essential to HCV replication. This review summarizes recent advances in the biochemical and structural understanding of HCV NS5B polymerase as well as in the development of antiviral agents targeting this important enzyme.
Cell Mol Life Sci 2002 Jun
PMID:RNA-dependent RNA polymerase encoded by hepatitis C virus: biomedical applications. 1216 21

Two fragments (1.9 and 1.8 kb) including, respectively, "structural" genes (A, B, and lysis polypeptide) and "replicase" gene, were obtained by reverse transcription PCR on the template of bacteriophage MS2 genome RNA. The fragments contained a common sequence which allowed the assembly of the entire functional genome sDNA. 1.8 kb fragment was subjected to two independent modifications: 1) so that the replicase gene could be replaced by other sequences no more than 1.5 kb in size and 2) it was inserted (on an artifician Tn-like structure) into E. coli chromosome. A system for replication of MS2-like corpuscles was thus created, containing a "shortened" genome and having extra genes. For extra genes, aminoglycoside-3'-phosphotransferase (kanamycin resistance) or a sequence of antiviral genetic program directed against hepatitis C virus were used.
Mol Gen Mikrobiol Virusol 2002
PMID:[RNA transduction by phage MS2 noninfectious virions]. 1218 20

Chronic hepatitis C is a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. Although current treatment options are limited, progress in understanding the molecular virology of hepatitis C has led to the identification of novel antiviral targets. Moreover, in vitro and in vivo model systems have been developed that allow systematic evaluation of new therapeutic strategies. This review details current concepts in molecular virology and emerging therapies for hepatitis C.
Trends Mol Med 2002 Oct
PMID:Hepatitis C: molecular virology and antiviral targets. 1238 70

Interferon (IFN) therapy has been associated with the development of Major Depressive Disorder (MDD) when given to patients with hepatitis C (HCV). The incidence, time course, risk factors, and treatment of IFN-induced MDD are poorly understood. The objectives of the present study were to determine the incidence of IFN-induced MDD, as well as to determine the efficacy of open-label antidepressant treatment, in particular selective serotonin reuptake inhibitors (SSRIs) for IFN-induced MDD. Thirty-nine HCV patients on IFN therapy were monitored weekly using the Beck Depression Inventory (BDI). Those who became depressed were treated with citalopram, a SSRI antidepressant. Main outcome measures included the incidence of IFN-induced MDD, as well as response rates to antidepressants in those patients who developed IFN-induced MDD. Our results showed that 13 of 39 patients (33%) developed IFN-induced MDD. There were no differences in age, gender, past history of MDD, or substance use between those who became depressed and those who did not. However, there were significantly fewer African American patients in the depressed group. Patients who developed IFN-induced MDD were on IFN therapy for an average of 12.1 weeks prior to the development of MDD. Eleven of 13 patients (85%) were responsive to antidepressant treatment. We conclude that IFN-induced MDD is common in HCV patients. Health care providers should follow IFN-treated HCV patients for the development of MDD, particularly between the 2nd and 5th months of IFN therapy. SSRIs, in particular citalopram, are an effective treatment for IFN-induced depression in HCV patients.
Mol Psychiatry 2002
PMID:A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C. 1239 46

The presenilin-type aspartic protease signal peptide peptidase (SPP) can cleave signal peptides within their transmembrane region. SPP is essential for generation of signal peptide-derived HLA-E epitopes in humans and is exploited by Hepatitis C virus for processing of the viral polyprotein. Here we analyzed requirements of substrates for intramembrane cleavage by SPP. Comparing signal peptides that are substrates with those that are not revealed that helix-breaking residues within the transmembrane region are required for cleavage, and flanking regions can affect processing. Furthermore, signal peptides have to be liberated from the precursor protein by cleavage with signal peptidase in order to become substrates for SPP. We propose that signal peptides require flexibility in the lipid bilayer to exhibit an accessible peptide bond for intramembrane proteolysis.
Mol Cell 2002 Oct
PMID:Requirements for signal peptide peptidase-catalyzed intramembrane proteolysis. 1241 11

In hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC), serum alanine aminotransferase (ALT) is frequently sustained on a high level after hepatectomy, with the formation of recurrent HCC tumors during follow-up periods. We investigated whether or not postoperative serum ALT level affects the interval before recurrence in hepatitis C virus-associated HCC. The subjects studied were 50 hepatectomized HCC patients who were HCV-Ab(+), and underwent a curable surgery in our Hospital from June 1990 to December 1999. We assessed the significance of the postoperative serum ALT level affecting tumor-free survival rates, as compared with other clinicopathological parameters, using univariate and multivariate Cox proportional hazard analysis. Thereafter, tumor-free and overall survival rates after hepatectomy were compared between high and low ALT groups, using Kaplan-Meier plotting and a log-rank test. The factor of ALT levels (a high or low ALT group) was most strongly associated with a tumor-free survival rate. Both tumor-free and overall survival rates were significantly poorer in the high ALT group than in the low ALT group among HCV-associated HCC cases (p<0.05). The results in this study suggest that postoperative hepatitis, which is indicated by sustained high ALT levels, may shorten the interval before recurrence in HCV-associated HCC. We should take care to control postoperative hepatitis to improve the prognoses of HCV-associated HCC cases.
Int J Mol Med 2002 Dec
PMID:Posthepatectomy hepatitis shortens tumor-free intervals in hepatitis C virus-associated hepatocellular carcinoma patients. 1243 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>