ArticleJournal of cellular and molecular medicine2019
HBx combined with AFB1 triggers hepatic steatosis via COX-2-mediated necrosome formation and mitochondrial dynamics disorder.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- COMPASS subunit Bre2 regulates chromatin remodeler Arp9 to control Aspergillus flavus aflatoxin synthesis and virulence.Nature communications · 2026Article
- The role of mycotoxins in lipid metabolism and homeostasis: a systematic review.Frontiers in toxicology · 2026Review
- Hepatitis B Virus and Hepatitis C Virus Affect Mitochondrial Function Through Different Metabolic Pathways, Explaining Virus-Specific Clinical Features of Chronic Hepatitis.The Journal of infectious diseases · 2024Article
- AFB1 Toxicity in Human Food and Animal Feed Consumption: A Review of Experimental Treatments and Preventive Measures.International journal of molecular sciences · 2024Review
- Nomogram for predicting overall survival of metastatic pancreatic cancer patients based on HBV infection and inflammatory-nutritional biomarkers.Frontiers in oncology · 2024Article
- RNA binding protein TIAR modulates HBV replication by tipping the balance of pgRNA translation.Signal transduction and targeted therapy · 2023Article
- Total Flavonoids ofAntioxidants (Basel, Switzerland) · 2023Article
- Intracellular antibody targeting HBx suppresses invasion and metastasis in hepatitis B virus-related hepatocarcinogenesis via protein phosphatase 2A-B56γ-mediated dephosphorylation of protein kinase B.Cell proliferation · 2022Article
- Hepatocyte-Derived Prostaglandin E2-Modulated Macrophage M1-Type Polarization via mTOR-NPC1 Axis-Regulated Cholesterol Transport from Lysosomes to the Endoplasmic Reticulum in Hepatitis B Virus x Protein-Related Nonalcoholic Steatohepatitis.International journal of molecular sciences · 2022Article
- Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can Be Partially Reversed by Antiviral Therapy.Microbiology spectrum · 2022Article
- Article
- Interferon-alpha responsible EPN3 regulates hepatitis B virus replication.Frontiers in medicine · 2022Article
- Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection.Frontiers in immunology · 2022Review
- AHR mediates the aflatoxin B1 toxicity associated with hepatocellular carcinoma.Signal transduction and targeted therapy · 2021Article
- Fowl Adenovirus Serotype 4 Induces Hepatic Steatosis via Activation of Liver X Receptor-α.Journal of virology · 2021Article
- Identification of Key Genes Associated With the Process of Hepatitis B Inflammation and Cancer Transformation by Integrated Bioinformatics Analysis.Frontiers in genetics · 2021Article
- MCPIP1 reduces HBV-RNA by targeting its epsilon structure.Scientific reports · 2020Article
- Aberrant lipid metabolism in hepatocellular carcinoma cells as well as immune microenvironment: A review.Cell proliferation · 2020Review
- Contamination of Aflatoxins Induces Severe Hepatotoxicity Through Multiple Mechanisms.Frontiers in pharmacology · 2020Review
- HBx combined with AFB1 triggers hepatic steatosis via COX-2-mediated necrosome formation and mitochondrial dynamics disorder.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure have been recognized as independent risk factors for the occurrence and exacerbation of hepatic steatosis but their combined impacts and the potential mechanisms remain to be further elucidated. Here, we showed that exposure to AFB1 impaired mitochondrial dynamics and increased intracellular lipid droplets (LDs) in the liver of HBV-transgenic mice in vivo and the hepatitis B virus X protein (HBx)-expressing human hepatocytes both ex vivo and in vitro. HBx combined with AFB1 exposure also up-regulated receptor interaction protein 1 (RIP1), receptor interaction protein 3 (RIP3) and activated mixed lineage kinase domain like protein (MLKL), providing evidence of necrosome formation in the hepatocytes. The shift of the mitochondrial dynamics towards imbalance of fission and fusion was rescued when MLKL was inhibited in the HBx and AFB1 co-treated hepatocytes. Most importantly, based on siRNA or CRISPR/Cas9 system, we found that the combination of HBx and AFB1 exposure increased cyclooxygenase-2 (COX-2) to mediate up-regulation of RIP3 and dynamin-related protein 1 (Drp1), which in turn promoted location of RIP3-MLKL necrosome on mitochondria, subsequently exacerbated steatosis in hepatocytes. Taken together, these findings advance the understanding of mechanism associated with HBx and AFB1-induced hepatic necrosome formation, mitochondrial dysfunction and steatosis and make COX-2 a good candidate for treatment.
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