Interventional Medicine and Applied Science
Volume/Issue:
Volume 1: Issue 1
Expression pattern of molecular chaperones after liver transplantation in hepatitis C positive recipients. Relation to serum HCV-RNA titers
Authors:
B. Nemes Clinic of Transplantation and Surgery, Semmelweis University, Budapest, Hungary
Clinic of Transplantation and Surgery, Semmelweis University, Baross u. 23–25, H-1087, Budapest, Hungary

Search for other papers by B. Nemes in
Current site
Google Scholar
PubMed Close
,
A. Doros Clinic of Transplantation and Surgery, Semmelweis University, Budapest, Hungary

Search for other papers by A. Doros in
Current site
Google Scholar
PubMed Close
,
Á. Holczbauer 2nd Institute of Pathology, Semmelweis University, Budapest, Hungary

Search for other papers by Á. Holczbauer in
Current site
Google Scholar
PubMed Close
,
E. Sárváry Clinic of Transplantation and Surgery, Semmelweis University, Budapest, Hungary

Search for other papers by E. Sárváry in
Current site
Google Scholar
PubMed Close
,
P. Nagy 1st Institute of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary

Search for other papers by P. Nagy in
Current site
Google Scholar
PubMed Close
,
G. Lengyel 2nd Clinic of Internal Medicine, Semmelweis University, Budapest, Hungary

Search for other papers by G. Lengyel in
Current site
Google Scholar
PubMed Close
,
A. Kiss 2nd Institute of Pathology, Semmelweis University, Budapest, Hungary

Search for other papers by A. Kiss in
Current site
Google Scholar
PubMed Close
, and
Zs. Schaff 2nd Institute of Pathology, Semmelweis University, Budapest, Hungary

Search for other papers by Zs. Schaff in
Current site
Google Scholar
PubMed Close
Pages:
35–40
Online Publication Date:
01 Dec 2009
Publication Date:
01 Dec 2009
Article Category:
Research Article
DOI:
https://doi.org/10.1556/imas.1.2009.1.5
Keywords:
liver transplantation; hepatitis C virus; chaperone; apoptosis; viral titer; RNA; recurrence; XBP; ATF6
Restricted access

Abstract

Hepatitis C (HCV) is one of the main causes of liver transplantation (OLT). Previously we have reported that high serum C RNA level correlates with the severity of histopathological signs and poor clinical outcome. The core antigen of virus C is known to interfere with chaperones in the hepatocytes, results in an endoplasmic reticulum (ER) stress. In this study HCV positive liver transplanted patients were evaluated, whether there are correlations among chaperone expression, recurrence and viral titer. Patients were enrolled after surviving the first month following OLT. Sera were collected regularly, and biopsies were taken on demand following OLT. The diagnosis of recurrent HCV was proven by Knodell-Ishak scoring. In this case ribavirin+interferon were initiated, and maintained for one year. All chaperones were upregulated in the transplanted liver graft showing recurrent hepatitis C disease. ATF6, GP96, GRP78, CNX and CLR chaperones were upregulated significantly compared to their levels in normal livers. Except for one chaperone, the level of upregulation did not correlate with the serum's HCV-RNA titre: the only difference between Group1 and 2 (RNA titre above and below 8.78 106 respectively) was that the level of ATF6 was 1.6 times higher in Group1 compared to Group2. The expression of all chaperones was reduced, and some even became downregulated after the interferon treatment. In accordance with the literature our results suggest that hepatitis C might induce apoptosis through ER-stress. Those cells exposed to a high C viral load, had a lower chance to be eliminated.

  • 1. E.P. Molmenti G.B.G. Klintmalm 2000 Hepatitis C recurrence after liver transplantation Liver Transpl 6 413 414.

  • 2. V. Di Martino et al.1997 Long-term longitudinal study of intrahepatic hepatitis C virus replication after liver transplantation Hepatology 26 1343 1350.

    • Search Google Scholar
    • Export Citation

  • 3. S. Fagiuali et al.2002 (AISF 2000-OLT Study Group): Liver Transplantation: The Italian experience Dig Liver Dis 34 619 620.

  • 4. B. Nemes et al.2005 Serum hepatitis C virus-ribonucleotide acid monitoring after liver transplantation. The Hungarian experience Dig. Liver. Dis. 37 68 69.

    • Search Google Scholar
    • Export Citation

  • 5. R. Sreekumar et al.2000 Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantation Hepatology 32 1125 1130.

    • Search Google Scholar
    • Export Citation

  • 6. V. Di Martino et al.2000 Influence of liver hepatitis C virus RNA and hepatitis C virus genotype on Fas-mediated apoptosis after liver transplantation for hepatitis C Transplantation 70 1390 1396.

    • Search Google Scholar
    • Export Citation

  • 7. A. Choukhi et al.1998 Involvement of Endoplasmic Reticulum Chaperones in the Folding of Hepatitis C Virus Glycoproteins J of Virology 72 3851 3858.

    • Search Google Scholar
    • Export Citation

  • 8. N. Di Domenico et al.1996 COBAS AMPLICOR: a fully automated RNA and DNA amplification and detection system for routine diagnostic PCR Clin Chem 42 1915 1923.

    • Search Google Scholar
    • Export Citation

  • 9. R.G. Knodell 1981 Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis Hepatology 1 431 435.

    • Search Google Scholar
    • Export Citation

  • 10. K. Ishak 1995 Histological grading and staging of chronic hepatitis J Hepatol 22 696 699.

  • 11. E.K. Drazan 2000 Molecular biology of hepatitis C infection Liver Transplantation 6 396 406.

  • 12. K.D. Tardif G. Waris A. Siddiqui 2005 Hepatitis C virus, ER stress and oxydative stress Trends in Microbiology 13 159 163.

  • 13. R.B. Ray et al.1997 Transcriptional repression of P53 promoter by hepatitis C virus core protein J Biol Chem 272 10983 10986.

  • 14. K.H. Lan et al.2002 HCV NS5A interacts with p53 and inhibits p53-mediated apoptosis Oncogene 21 4801 4811.

  • 15. A. de Beeck et al.2004 Characterization of Functional Hepatitis C Virus Envelope Glycoproteins J of Virology 78 994 3002.

  • 16. J.-C. Meunier et al.1999 Analysis of the glycosylation sites of hepatitis C virus (HCV) glycoprotein E1 and the influence of E1 glycans on the formation of the HCV glycoprotein complex J of Gen Virology 80 887 896.

    • Search Google Scholar
    • Export Citation

  • 17. R. Kaufman 1999 Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls Genes Dev 13 1211 1233.

    • Search Google Scholar
    • Export Citation

  • 18. H. Pahl 1999 Signal transduction from the endoplasmic reticulum to the cell nucleus Physiol. Rev. 79 683 699.

  • 19. G. Waris K.D. Tardif A. Siddiqui 2002 Endoplasmic reticulum (ER) stress: hepatitis C virus induces an ER-nucleus signal transduction pathway and activates NF-kappaB and STAT-3 Biochem Pharmacol 64 1425 1430.

    • Search Google Scholar
    • Export Citation

  • 20. A.R. Ciccaglione et al.2005 M Activation of endoplasmic reticulum stress response by hepatitis C virus proteins Arch Virol 150 1339 1356.

    • Search Google Scholar
    • Export Citation

  • 21. H. Yoshida et al.2001 XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor Cell 107 881 891.

    • Search Google Scholar
    • Export Citation

  • 22. S.H. Lee et al.2008 A molecular chaperone glucose-regulated protein 94 blocks apoptosis induced by virus infection Hepatology 47 854 866.

    • Search Google Scholar
    • Export Citation

  • 23. T. Okamoto et al.2006 Hepatitis C virus RNA replication is regulated by FKBP8 and Hsp90 EMBO J 25 5015 5025.

  • 24. T. Okamoto et al.2008 A single-amino-acid mutation in hepatitis C virus NS5A disrupting FKBP8 interaction impairs viral replication J Virol 82 3480 3489.

    • Search Google Scholar
    • Export Citation

  • 25. N.L. Benali-Furet et al.2005 Hepatitis C vírus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion Oncogene 24 4921 4933.

    • Search Google Scholar
    • Export Citation

  • 26. S.W. Chan P.A. Egan 2005 Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein response FASEB J 19 1510 1512.

    • Search Google Scholar
    • Export Citation

  • 27. H. Marusawa et al.1999 Hepatitis C virus core protein inhibits Fas- and Tumor Necrosis Factor alpha-mediated apoptosis via NF-kB activation J Virol 73 4713 4720.

    • Search Google Scholar
    • Export Citation

  • 28. A. Emadali et al.2005 Distinct endoplasmic reticulum stress responses are triggered during human liver transplantation J Pathol 207 111 118.

    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
Cover Interventional Medicine and Applied Science
Interventional Medicine and Applied Science
Print ISSN:
2061-1617
Online ISSN:
2061-5094

2019  
Scimago
H-index		 11
Scimago
Journal Rank		 0,220
Scimago
Quartile Score		 Medicine (miscellaneous) Q3
Scopus
Cite Score		 155/133=1,2
Scopus
Cite Score Rank		 General Medicine 199/529 (Q2)
Scopus
SNIP		 0,343
Scopus
Cites		 206
Scopus
Documents		 23

 

Interventional Medicine and Applied Science
Language English
Size  
Year of
Foundation		 2009
Publication
Programme		 changed title
Volumes
per Year		  
Issues
per Year		  
Founder Akadémiai Kiadó
Founder's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address		 H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher		 Chief Executive Officer, Akadémiai Kiadó
ISSN 2061-1617 (Print)
ISSN 2061-5094 (Online)

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Apr 2024 46 0 0
May 2024 10 0 0
Jun 2024 29 0 0
Jul 2024 13 0 0
Aug 2024 25 0 0
Sep 2024 14 0 0
Oct 2024 2 0 0