Journalartikel

Jahr der Veröffentlichung: 2016

Seiten: 20312-20323

Zeitschrift: Oncotarget

Bandnummer: 7

Heftnummer: 15

eISSN: 1949-2553

Open Access Status: Gold

DOI Link: https://doi.org/10.18632/oncotarget.7950

Verlag: Impact Journals

Abstract: 
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 eIF2a (Eukaryotic Initiation Factor 2a) and splicing of XBP1 (X-box binding protein 1) was observed. CB1(-/-) HepG2 cells did not show any ER stress activation. Inhibition of CB1yreceptor 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.

Harvard-Zitierstil: Montalbano, R., Honrath, B., Wissniowski, T., Elxnat, M., Roth, S., Ocker, M., et al. (2016) Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells, Oncotarget, 7(15), pp. 20312-20323. https://doi.org/10.18632/oncotarget.7950

APA-Zitierstil: Montalbano, R., Honrath, B., Wissniowski, T., Elxnat, M., Roth, S., Ocker, M., Quint, K., Churin, Y., Roederfeld, M., Schroeder, D., Glebe, D., Roeb, E., & Di Fazio, P. (2016). Exogenous hepatitis B virus envelope proteins induce endoplasmic reticulum stress: involvement of cannabinoid axis in liver cancer cells. Oncotarget. 7(15), 20312-20323. https://doi.org/10.18632/oncotarget.7950