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Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells
HBV represents the most common chronic viral infection and major cause of hepatocellular carcinoma (HCC), although its exact role in liver tumorigenesis is unclear. Massive storage of the small (SHBs), middle (MHBs) and large surface (LHBs) HBV envelope proteins leads to cell stress and sustained in...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991457/ https://www.ncbi.nlm.nih.gov/pubmed/26967385 http://dx.doi.org/10.18632/oncotarget.7950 |
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author | Montalbano, Roberta Honrath, Birgit Wissniowski, Thaddeus Till Elxnat, Moritz Roth, Silvia Ocker, Matthias Quint, Karl Churin, Yuri Roederfeld, Martin Schroeder, Dirk Glebe, Dieter Roeb, Elke Fazio, Pietro Di |
author_facet | Montalbano, Roberta Honrath, Birgit Wissniowski, Thaddeus Till Elxnat, Moritz Roth, Silvia Ocker, Matthias Quint, Karl Churin, Yuri Roederfeld, Martin Schroeder, Dirk Glebe, Dieter Roeb, Elke Fazio, Pietro Di |
author_sort | Montalbano, Roberta |
collection | PubMed |
description | HBV represents the most common chronic viral infection and major cause of hepatocellular carcinoma (HCC), although its exact role in liver tumorigenesis is unclear. Massive storage of the small (SHBs), middle (MHBs) and large surface (LHBs) HBV envelope proteins leads to cell stress and sustained inflammatory responses. Cannabinoid (CB) system is involved in the pathogenesis of liver diseases, stimulating acute and chronic inflammation, liver damage and fibrogenesis; it triggers endoplasmic reticulum (ER) stress response. The aim of our work was to investigate the activation of ER stress pathway after ectopic HBV envelope proteins expression, in liver cancer cells, and the role exerted by CB receptors. PCR, immunofluorescence and western blotting showed that exogenous LHBs and MHBs induce a clear ER stress response in Huh-7 cells expressing CB1 receptor. Up-regulation of the chaperone BiP/GRP78 (Binding Immunoglobulin Protein/Glucose-Regulated Protein 78) and of the transcription factor CHOP/GADD153 (C/EBP Homologous Protein/Growth Arrest and DNA Damage inducible gene 153), phosphorylation of PERK (PKR-like ER Kinase) and eIF2α (Eukaryotic Initiation Factor 2α) and splicing of XBP1 (X-box binding protein 1) was observed. CB1(−/−) HepG2 cells did not show any ER stress activation. Inhibition of CB1 receptor counteracted BiP expression in transfected Huh-7 and in HBV(+) PLC/PRF/5 cells; whereas no effect was observed in HBV(−) HLF cells. These results suggest that HBV envelope proteins are able to induce the ER stress pathway. CB1 expression is directly correlated with ER stress function. Further investigations are needed to clarify the involvement of cannabinoid in HCC progression after HBV infection. |
format | Online Article Text |
id | pubmed-4991457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-49914572016-09-01 Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells Montalbano, Roberta Honrath, Birgit Wissniowski, Thaddeus Till Elxnat, Moritz Roth, Silvia Ocker, Matthias Quint, Karl Churin, Yuri Roederfeld, Martin Schroeder, Dirk Glebe, Dieter Roeb, Elke Fazio, Pietro Di Oncotarget Research Paper HBV represents the most common chronic viral infection and major cause of hepatocellular carcinoma (HCC), although its exact role in liver tumorigenesis is unclear. Massive storage of the small (SHBs), middle (MHBs) and large surface (LHBs) HBV envelope proteins leads to cell stress and sustained inflammatory responses. Cannabinoid (CB) system is involved in the pathogenesis of liver diseases, stimulating acute and chronic inflammation, liver damage and fibrogenesis; it triggers endoplasmic reticulum (ER) stress response. The aim of our work was to investigate the activation of ER stress pathway after ectopic HBV envelope proteins expression, in liver cancer cells, and the role exerted by CB receptors. PCR, immunofluorescence and western blotting showed that exogenous LHBs and MHBs induce a clear ER stress response in Huh-7 cells expressing CB1 receptor. Up-regulation of the chaperone BiP/GRP78 (Binding Immunoglobulin Protein/Glucose-Regulated Protein 78) and of the transcription factor CHOP/GADD153 (C/EBP Homologous Protein/Growth Arrest and DNA Damage inducible gene 153), phosphorylation of PERK (PKR-like ER Kinase) and eIF2α (Eukaryotic Initiation Factor 2α) and splicing of XBP1 (X-box binding protein 1) was observed. CB1(−/−) HepG2 cells did not show any ER stress activation. Inhibition of CB1 receptor counteracted BiP expression in transfected Huh-7 and in HBV(+) PLC/PRF/5 cells; whereas no effect was observed in HBV(−) HLF cells. These results suggest that HBV envelope proteins are able to induce the ER stress pathway. CB1 expression is directly correlated with ER stress function. Further investigations are needed to clarify the involvement of cannabinoid in HCC progression after HBV infection. Impact Journals LLC 2016-03-07 /pmc/articles/PMC4991457/ /pubmed/26967385 http://dx.doi.org/10.18632/oncotarget.7950 Text en Copyright: © 2016 Montalbano et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Montalbano, Roberta Honrath, Birgit Wissniowski, Thaddeus Till Elxnat, Moritz Roth, Silvia Ocker, Matthias Quint, Karl Churin, Yuri Roederfeld, Martin Schroeder, Dirk Glebe, Dieter Roeb, Elke Fazio, Pietro Di Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
title | Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
title_full | Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
title_fullStr | Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
title_full_unstemmed | Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
title_short | Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
title_sort | exogenous hepatitis b virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4991457/ https://www.ncbi.nlm.nih.gov/pubmed/26967385 http://dx.doi.org/10.18632/oncotarget.7950 |
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