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

• Published in: World journal of gastroenterology : WJG Vol. 15; no. 36; pp. 4499 - 4510
• Main Authors: Hou, Wei-Hong, Rossi, Lisa, Shan, Ying, Zheng, Jian-Yu, Lambrecht, Richard-W, Bonkovsky, Herbert-L
• Format: Journal Article
• Language: English
• Published: United States The Cannon Research Center and the Liver, Digestive Disease, and Metabolism Laboratory,Carolinas Medical Center, Charlotte, NC 28203, United States 28.09.2009; The University of North Carolina, Charlotte 28223, United States; The University of North Carolina, Chapel Hill, NC 27514, United States; Departments of Medicine, and Molecular, Microbial & Structural Biology, University of Connecticut Health Center, Farmington, CT 06030, United States; The University of North Carolina, Charlotte, NC 28223, United States%Department of Medicin e,University of Connecticut Health Center, Farmington, CT 06030,United States%Department of Molecular, Microbial & Structural Biology, University of Connecticut Health Center, Farmington,CT 06030, United States%The Cannon Research Center and the Liver, Digestive Disease, and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC 28203, United States; Department of Medicine of the University of Massachusetts Medical School, Worcester, MA 01655, United States; The WJG Press and Baishideng
• Subjects: Basic-Leucine Zipper Transcription Factors - drug effects; Basic-Leucine Zipper Transcription Factors - metabolism; Brief; Carcinoma, Hepatocellular - virology; Cell Line, Tumor; Deferoxamine - pharmacology; Fanconi Anemia Complementation Group Proteins - drug effects; Fanconi Anemia Complementation Group Proteins - metabolism; Ferric Compounds - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Viral - drug effects; Heme Oxygenase-1 - drug effects; Heme Oxygenase-1 - genetics; Heme Oxygenase-1 - metabolism; Hepacivirus - drug effects; Hepacivirus - genetics; Hepacivirus - metabolism; Hepatitis C - enzymology; Hepatitis C - genetics; Hepatitis C - virology; Humans; Iron - pharmacology; Liver Neoplasms - virology; NF-E2-Related Factor 2 - drug effects; NF-E2-Related Factor 2 - metabolism; Nitrilotriacetic Acid - analogs & derivatives; Nitrilotriacetic Acid - metabolism; Oxidative Stress; Reactive Oxygen Species - metabolism; RNA, Messenger - metabolism; RNA, Small Interfering - metabolism; Viral Proteins - metabolism; Bach1; Nuclear factor-erythroid 2-related factor 2; Heme oxygenase-1; Core protein of hepatitis C virus; Iron; Oxidative tress; Hepatitis C; Nonstructural 5A protein of hepatitis C virus; Deferoxamine
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.15.4499

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. 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. 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. 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.