Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

21 September 2017 : Laboratory Research  

Hepatitis C Virus Infection Increases c-Jun N-Terminal Kinase (JNK) Phosphorylation and Accentuates Hepatocyte Lipoapoptosis

Hiroko Takaki1ABCDEF, Yuko Akazawa23A*, Youko Kido2B, Mami Morishita1BC, Takuya Honda1D, Hidetaka Shibata1D, Satoshi Miuma1D, Hisamitsu Miyaaki1AD, Naota Taura1D, Hisayoshi Kondo4C, Kazuhiko Nakao1DG

DOI: 10.12659/MSM.903210

Med Sci Monit 2017; 23:4526-4532

Abstract

BACKGROUND: Hepatitis C virus (HCV) infection and metabolic diseases including nonalcoholic steatohepatitis (NASH) exhibit a complex interplay. Although free fatty acid-mediated apoptosis is a prominent feature of NASH, the impact of HCV infection on hepatocyte lipotoxicity has remained largely unexplored. The study aimed at identifying whether infection by HCV affected the apoptotic pathway in hepatocytes during fatty acid assault.

MATERIAL AND METHODS: OR6 cells, which are derived from human hepatocellular carcinoma Huh-7 cells and harbor a full-length HCV RNA genome replication system, were treated with palmitate. Apoptosis was examined by 4’,6-diamidino-2-phenylindole staining. Activation and expression of JNK, Bim, cIAP-1, and Mcl-1 were examined by immunoblotting. mRNA expression of CHOP, a major player in endoplasmic reticulum stress-mediated apoptosis, was assessed by real-time PCR.

RESULTS: Palmitate-induced hepatocyte apoptosis was significantly enhanced in OR6 cells compared to cured cells, in which the HCV genome had been eradicated by treatment with interferon-α. Although basal expression of CHOP mRNA was enhanced in OR6 cells compared to cured cells, it was similarly upregulated in both cell lines following palmitate treatment. Notably, palmitate-induced JNK phosphorylation was accentuated in OR6 cells compared to cured cells. Inhibition of JNK with SP600125 attenuated palmitate-induced apoptosis. Palmitate-mediated upregulation of BH3-only protein Bim, which acts downstream of JNK, was also enhanced in OR6 cells compared to cured cells. In contrast, Mcl-1 and cIAP-1 were equally reduced in OR6 cells and cured cells following palmitate treatment.

CONCLUSIONS: These findings suggest that during lipoapoptosis, HCV infection may enhance hepatocyte toxicity by increasing JNK phosphorylation.

Keywords: Cell Death, Fatty Acids, Nonesterified, Fatty Liver, Hepatitis C, Chronic

Add Comment 0 Comments

Editorial

01 July 2024 : Editorial  

Editorial: The Global Threats of Increasing Antimicrobial Resistance Require New Approaches to Drug Development, Including Molecular Antimicrobial Adjuvants

Dinah V. Parums

DOI: 10.12659/MSM.945583

Med Sci Monit 2024; 30:e945583

0:00

In Press

Database Analysis  

Local Government Initiatives: A Comprehensive Analysis of Infertility Diagnostic and Treatment Programs in ...

Med Sci Monit In Press; DOI: 10.12659/MSM.943976  

0:00

Clinical Research  

Gender-Specific Risk Factors for Asymmetric Bone Density in Adult Degenerative Lumbar Scoliosis: A Retrospe...

Med Sci Monit In Press; DOI: 10.12659/MSM.944137  

Review article  

Innovative Approaches to Enhance and Measure Medication Adherence in Chronic Disease Management: A Review

Med Sci Monit In Press; DOI: 10.12659/MSM.944605  

Clinical Research  

Effects of Ozone Disc Nucleolysis in Management of Herniated Lumbar Intervertebral Disc: A Retrospective Si...

Med Sci Monit In Press; DOI: 10.12659/MSM.944645  

Most Viewed Current Articles

17 Jan 2024 : Review article   3,694,697

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

14 Dec 2022 : Clinical Research   1,585,228

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels

DOI :10.12659/MSM.937990

Med Sci Monit 2022; 28:e937990

0:00

16 May 2023 : Clinical Research   690,866

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Jan 2022 : Editorial   50,699

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

0:00

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750