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Cited by 35Heme Oxygenase-1 and Carbon MonoxideHepatitis C virus researchIron Metabolism and Disorders

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Iron increases HMOX1 and decreases hepatitis C viral expression in HCV-expressing cells

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Hou, Wei-Hong, Rossi, Lisa, Shan, Ying, Zheng, Jian-Yu, Lambrecht, Richard W, Bonkovsky, Herbert L·2009·World Journal of Gastroenterology
DOI 10.3748/wjg.15.4499PMC PMC2751994
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Abstract

AIM: To investigate effects of iron on oxidative stress, heme oxygenase-1 (HMOX1) and hepatitis C viral (HCV) expression in human hepatoma cells stably expressing HCV proteins. METHODS: Effects of iron on oxidative stress, HMOX1, and HCV expression were assessed in CON1 cells. Measurements included mRNA by quantitative reverse transcription-polymerase chain reaction, and protein levels by Western blots. RESULTS: Iron, in the form of ferric nitrilotriacetate, increased oxidative stress and up-regulated HMOX1 gene expression. Iron did not affect mRNA or protein levels of Bach1, a repressor of HMOX1. Silencing the up-regulation of HMOX1 nuclear factor-erythroid 2-related factor 2 (Nrf2) by Nrf2-siRNA decreased FeNTA-mediated up-regulation of HMOX1 mRNA levels. These iron effects were completely blocked by deferoxamine (DFO). Iron also significantly decreased levels of HCV core mRNA and protein by 80%-90%, nonstructural 5A mRNA by 90% and protein by about 50% in the Con1 full length HCV replicon cells, whereas DFO increased them. CONCLUSION: Excess iron up-regulates HMOX1 and down-regulates HCV gene expression in hepatoma cells. This probably mitigates liver injury caused by combined iron overload and HCV infection.

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  • Ingestion of even mild to moderate amounts of alcohol can increase iron overload, with the iron being localized in Kupffer cells and hepatocytes.

    “Hou et al., (2009) reported that ingestion of even mild to moderate amounts of alcohol can increase iron overload, with the iron being localized in Kupffer cells and hepatocytes.”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Hou et al., (2009)

  • Hepcidin expression is not responsive to body iron levels in alcohol consumption.

    “To make matters worse, hepcidin expression is not responsive to body iron levels in alcohol consumption (Hou et al., 2009).”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Hou et al., 2009

  • Alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP activity, thus dysregulating iron homeostasis.

    “Although the mechanisms underlying iron accumulation are not well understood, it has been reported that alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP activity, thus dysregulating iron homeostasis (Hou et al., 2009;Harrison-Findik, 2009).”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Hou et al., 2009

  • Hepatic iron overload is common in many liver diseases where iron is a risk factor in disease progression.

    “Hepatic iron overload is common in many liver diseases where iron is a risk factor in disease progression (Hou et al., 2009).”

    From Iron, Oxidative Stress and Health (2012) · cites this paper as Hou et al., 2009

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  • Iron, Oxidative Stress and Health

    Udipi, S., Ghugre, P., & Gokhale, C. (2012) · Oxidative Stress - Molecular Mechanisms and Biological Effects · doi:10.5772/34975 · Cited by 17

    “…iron accumulation are not well understood, it has been reported that alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP┙ activity, thus dysregulating iron homeostasis (Hou et al., 2009; Harrison-Findik, 2009).”
    BackgroundInfluential

Metadata

Authors
Hou, W.-H., Rossi, L., Shan, Y., Zheng, J.-Y., Lambrecht, R. W., & Bonkovsky, H. L.
Affiliations
  • Carolinas Medical Center (US)
  • Carolinas Healthcare System (US)
ORCID
Venue
World Journal of Gastroenterology
Publisher
Baishideng Publishing Group Inc.
Published
2009
Volume
15
Issue
36
Pages
4499
ISSN
1007-9327 (ISSN-L)
DOI
10.3748/wjg.15.4499
PMC
PMC2751994
OpenAlex
W2042096335
Cited by
35
References
5
Citations by year
2024: 1 · 2022: 3 · 2021: 1 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 7 · 2013: 2 · 2012: 6
FWCI
1.75
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • World Journal of Gastroenterology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Universität Heidelberg
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK RO 1-38825, DK NO129236, UO1 DK 06193)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
  • Health Sciences › Medicine › Hepatology › Hepatitis C virus research
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Keywords
iron, heme oxygenase-1, hepatitis C virus, oxidative stress, Nrf2, deferoxamine, ferric nitrilotriacetate, HCV core protein, NS5A, HCV replicon, hepatoma cells, iron overload, liver injury, BACH1
MeSH terms
Deferoxamine, Ferric Compounds, Hepatitis C, Carcinoma, Hepatocellular, Humans, Iron, Liver Neoplasms, Nitrilotriacetic Acid, RNA, Messenger, Viral Proteins, Gene Expression Regulation, Viral, Gene Expression Regulation, Neoplastic, Hepacivirus, Reactive Oxygen Species, Oxidative Stress, RNA, Small Interfering, Cell Line, Tumor, Basic-Leucine Zipper Transcription Factors, NF-E2-Related Factor 2, Heme Oxygenase-1, Fanconi Anemia Complementation Group Proteins

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