ArticleGastroenterology2010
Zinc mesoporphyrin induces rapid proteasomal degradation of hepatitis C nonstructural 5A protein in human hepatoma cells.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
- Preoperative Zinc Deficiency as a Novel Prognostic Predictor for Postoperative Recurrence in Hepatocellular Carcinoma.Nutrients · 2026Article
- Human Viral Oncoproteins and Ubiquitin-Proteasome System.Global medical genetics · 2024Review
- Progress, evolving therapeutic/diagnostic approaches, and challenges in the management of hepatitis C virus infections.Archives of virology · 2022Review
- Article
- USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation.Journal of virology · 2019Article
- Hepatitis C Virus Downregulates Ubiquitin-Conjugating Enzyme E2S Expression To Prevent Proteasomal Degradation of NS5A, Leading to Host Cells More Sensitive to DNA Damage.Journal of virology · 2019Article
- SPSB2 inhibits hepatitis C virus replication by targeting NS5A for ubiquitination and degradation.PloS one · 2019Article
- Article
- Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A.Nature communications · 2016Article
- Y-Box Binding Protein 1 Stabilizes Hepatitis C Virus NS5A via Phosphorylation-Mediated Interaction with NS5A To Regulate Viral Propagation.Journal of virology · 2015Article
- Hepatitis C Virus Nonstructural Protein 5A Inhibits MG132-Induced Apoptosis of Hepatocytes in Line with NF-κB-Nuclear Translocation.PloS one · 2015Article
- Proteasome- and ethanol-dependent regulation of HCV-infection pathogenesis.Biomolecules · 2014Review
- Modulation of hepatitis C virus genome encapsidation by nonstructural protein 4B.Journal of virology · 2013Article
- Heme status affects human hepatic messenger RNA and microRNA expression.World journal of gastroenterology · 2013Article
- Roles of the two distinct proteasome pathways in hepatitis C virus infection.World journal of virology · 2012Article
- Heme and HO-1 Inhibition of HCV, HBV, and HIV.Frontiers in pharmacology · 2012Article
- miR-196 regulates axial patterning and pectoral appendage initiation.Developmental biology · 2011Article
- The let-7 microRNA enhances heme oxygenase-1 by suppressing Bach1 and attenuates oxidant injury in human hepatocytes.Biochimica et biophysica actaArticle
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsThe nonstructural 5A (NS5A) protein of hepatitis C virus (HCV) plays a critical role in HCV replication and is an attractive target for the therapy of HCV infection. So far, little is known about the posttranslational regulation of NS5A protein and its precise role in HCV RNA replication. Our objectives were to elucidate the down-regulation of NS5A protein and HCV RNA replication by zinc mesoporphyrin (ZnMP) and the mechanism by which this process occurs.
methodsHuman hepatoma cells expressing HCV proteins were used to investigate the posttranslational regulation of ZnMP on NS5A protein by Western blots and immunoprecipitation. Real-time quantitative reverse transcription polymerase chain reaction was used to determine the effects of ZnMP on HCV RNA replication.
resultsZnMP selectively and markedly down-regulated NS5A protein levels by increasing degradation of NS5A protein (half-life fell from 18.7 hours to 2.7 hours). The proteasome inhibitors epoxomicin and MG132 significantly abrogated degradation of NS5A protein by ZnMP without affecting levels of NS5A in the absence of ZnMP. Analysis of immunoprecipitates with an antiubiquitin antibody revealed polyubiquitination of NS5A, suggesting that ZnMP induces ubiquitination of NS5A protein. In addition, 10 micromol/L of ZnMP reduced HCV replication by approximately 63% in the Con1 replicon cells, approximately 70% in J6/Japanese fulminant hepatitis 1 HCV-transfected cells, and approximately 90% in J6/Japanese fulminant hepatitis 1 HCV-infected cells without affecting cell viability.
conclusionsZnMP produces a rapid and profound down-regulation of the NS5A protein by enhancing its polyubiquitination and proteasome-dependent catabolism. ZnMP may hold promise as a novel agent to treat HCV infection.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.