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HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species

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Authors
Gu, Jin-Mo; Lim, Seung Oe; Oh, Sae Jin; Yoon, So-Mi; Sung, Je Kyeong; Jung, Guhung
Issue Date
2008-02-08
Publisher
Elsevier
Citation
Virus Res. 133 (2), 167-177
Keywords
IronHBxROSIRP1Total iron levelLIP
Abstract
Hepatitis B virus X protein (HBx) is involved in viral metabolism and progression of liver disease. Iron metabolism plays a significant role in liver disease. In this report, to elucidate the relationship between iron metabolism and HBx, we established the Huh7 cell lines in which HBx was stably expressed (Huh7-HBx). In Huh7-HBx, we observed that transferrin receptor 1 (TfR1) expression decreased and ferritin heavy chain (FtH) expression increased as well as reactive oxygen species (ROS) level increased. We also found that these modulations were caused by the downregulation of iron regulatory protein 1 (IRP1). Furthermore, the levels of total iron and labile iron pool (LIP) were altered in Huh7-HBx. In addition, antioxidant N-acetylcystein (NaC) increased IRP1 expression by depleting HBx-induced ROS. We also confirmed these alterations of TfR1 and FtH in the primary hepatocytes of HBx transgenic mice and in HepG2.2.15 cells that constitutively replicate the intact HBV genome. In conclusion, these results suggest that HBx modulates iron metabolism via ROS leading to pathological status in liver diseases.
ISSN
0168-1702
Language
English
URI
http://hdl.handle.net/10371/7886
DOI
https://doi.org/10.1016/j.virusres.2007.12.014
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College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
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