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

查看全文 作　　者：Wei-Hong [1]Hou;Lisa [2]Rossi;Ying [3]Shan;Jian-Yu [1]Zheng;Richard W [2]Lambrecht;Herbert L [4]Bonkovsky

机构地区：[1]The Cannon Research Center and the Liver, Digestive Disease, and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC 28203, United States; The University of North Carolina, Charlotte, NC 28223, United States;[2]Richard W Lambrecht, Department of Medicin e, University of Connecticut Health Center, Farmington, CT 06030, United States;[3]Department of Molecular, Microbial & Structural Biology, University of Connecticut Health Center, Farmington, CT 06030, United States;[4]The Cannon Research Center and the Liver, Digestive Disease, and Metabolism Laboratory, Carolinas Medical Center, Charlotte, NC 28203, United States; 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; Department of Medicine of the University of Massachusetts Medical School, Worcester, MA 01655, United States

出　　处：《World Journal of Gastroenterology》索引2009年第15卷第36期,共12页

基　　金：Supported by Grant(DK RO1 38825) and contracts(DK NO129236 and UO1 DK 06193)from the National Institutes of Health(NIDDK) 摘　　要：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. 关键词：丙型肝炎病毒肝癌细胞逆转录聚合酶链反应血红素氧化酶-1 MRNA水平铁蛋白质水平氧化应激

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

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