Hepatitis C virus core triggers apoptosis in liver cells by inducing ER stress and ER calcium depletion View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-07

AUTHORS

Naoual L Benali-Furet, Mounia Chami, Ludivine Houel, Francesca De Giorgi, Fabienne Vernejoul, David Lagorce, Louis Buscail, Ralf Bartenschlager, François Ichas, Rosario Rizzuto, Patrizia Paterlini-Bréchot

ABSTRACT

Hepatitis C virus (HCV) core, known to be involved in liver carcinogenesis, is processed in the endoplasmic reticulum (ER). We thus investigated the impact of three HCV core isolates on ER stress, ER calcium signalling and apoptosis. We show that HCV core constructs trigger hyperexpression of Grp78/BiP, Grp 94, calreticulin and sarco/endoplasmic reticulum calcium ATPase, inducing ER stress. By using the ER-targeted aequorin calcium probe, we found that ER calcium depletion follows ER stress in core-expressing cells. HCV core induces apoptosis through overexpression of the CHOP/GADD153 proapoptotic factor, Bax translocation to mitochondria, mitochondrial membrane depolarization, cytochrome c release, caspase-3 and PARP cleavage. Furthermore, reversion of HCV core-induced ER calcium depletion (by transfection of SERCA2) completely abolished mitochondrial membrane depolarization, suggesting that both ER stress (through CHOP overexpression) and calcium signalling play a major role in the HCV core-mediated control of apoptosis. ER stress and apoptosis were also found in a proportion of HCV-full-length replicon-expressing cells and in the liver of HCV core transgenic mice. In conclusion, our data demonstrate that HCV core deregulates the control of apoptosis by inducing ER stress and ER calcium depletion providing new elements to understand the mechanisms involved in HCV-related liver chronic diseases. More... »

PAGES

1208673

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1208673

DOI

http://dx.doi.org/10.1038/sj.onc.1208673

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1050186773

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15897896


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