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

Abstract

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.

Iron, Oxidative Stress and Health

“…Thus iron and alcohol together contribute to and aggravate liver disease (Harrison-Findik, 2007). Although the mechanisms underlying iron accumulation are not well understood, it has been reported that alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP activity, thus dysregulating iron homeostasis (Hou et al, 2009;Harrison-Findik, 2009). To make matters worse, hepcidin expression is not responsive to body iron levels in alcohol consumption (Hou et al, 2009).…”

“…Although the mechanisms underlying iron accumulation are not well understood, it has been reported that alcohol-induced oxidative stress in hepatocytes downregulates hepcidin expression in liver, by altering transcription factor C/EBP activity, thus dysregulating iron homeostasis (Hou et al, 2009;Harrison-Findik, 2009). To make matters worse, hepcidin expression is not responsive to body iron levels in alcohol consumption (Hou et al, 2009). H 2 O 2 increases the expression of TfRI leading to iron accumulation and thus may support ALD progression (Girelli et al, 2009).…”

“…Mitochondrial dysfunction has been reported to possibly play an important role in development of non-alcoholic fatty liver disease (NAFLD) and non alcoholic steatohepatitis (NASH). Hou et al, (2009) reported that ingestion of even mild to moderate amounts of alcohol can increase iron overload, with the iron being localized in Kupffer cells and hepatocytes. On the other hand, alcohol metabolism to form acetaldehyde generates ROS.…”

“…Hepatic iron overload is common in many liver diseases where iron is a risk factor in disease progression (Hou et al, 2009). Hemochromatosis is a well-defined syndrome characterized by normal iron-driven erythropoiesis and toxic accumulation of iron in parenchymal cells of vital organs that can be caused by mutations in any gene that limits iron entry into the blood.…”

Regulation of the HMOX1 gene by the transcription factor AP-2δ with unique DNA binding site

“…The HMOX1 gene is under complex regulation and is markedly upregulated by heme, the physiological substrate for the HMOX1 protein, by iron and other transition metallic ions, and by oxidative and heat stress and other stressful perturbations (12)(13)(14). Regulation of the HMOX1 gene expression is associated in part with alterations in the levels of several transcription factors, including Bach1 and nuclear factor-erythroid 2-related factor 2 (Nrf2) (15)(16)(17)(18). Ap-2δ was identified as a new activating transcription factor of HMOX1.…”