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

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:zhoujiayan
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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. AIM: To investigate the 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. I did 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. The iron effects was also 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, wherea s 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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