HBx modulates iron regulatory protein 1-mediated iron metabolism via reactive oxygen species.
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.
Gu
Jin-Mo
JM
Department of Biological Sciences, Seoul National University, 56-1 Shillim-dong, Kwanak-gu, Seoul 151-747, Republic of Korea.
Lim
Seung Oe
SO
Oh
Sae Jin
SJ
Yoon
So-Mi
SM
Seong
Je Kyung
JK
Jung
Guhung
G
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001052:Apoferritins / Q000378:metabolism; D002478:Cells, Cultured; D005293:Ferritins; D015967:Gene Expression Regulation, Viral; D022781:Hepatocytes; D006801:Humans; D007501:Iron / Q000378:metabolism; D035941:Iron Regulatory Protein 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
D015703:Antigens, CD; C068126:CD71 antigen; D017382:Reactive Oxygen Species; D011990:Receptors, Transferrin; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D005293:Ferritins; D001052:Apoferritins; D007501:Iron; D035941:Iron Regulatory Protein 1