Oxidative stress and hepatic Nox proteins in chronic hepatitis C and hepatocellular carcinoma
| Autor: | Nicole L. B. Corder, Yiyan Wang, Bhargav Koduru, Jinah Choi |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Cirrhosis
Carcinoma Hepatocellular medicine.disease_cause Biochemistry Article Physiology (medical) medicine Animals Humans NADPH oxidase biology Chemistry Liver Neoplasms NOX4 NADPH Oxidases Hepatitis C Chronic medicine.disease digestive system diseases Oxidative Stress Hepatocellular carcinoma Immunology biology.protein Liver cancer Hepatic fibrosis Carcinogenesis Oxidative stress |
| Zdroj: | Free radical biologymedicine. 72 |
| ISSN: | 1873-4596 |
| Popis: | Hepatocellular carcinoma (HCC) is the most common liver cancer and a leading cause of cancer-related mortality in the world. Hepatitis C virus (HCV) is a major etiologic agent of HCC. A majority of HCV infections lead to chronic infection that can progress to cirrhosis and eventually, HCC and liver failure. A common pathogenic feature present in HCV infection, and other conditions leading to HCC, is oxidative stress. HCV directly increases superoxide and H2O2 formation in hepatocytes by elevating Nox protein expression and sensitizing mitochondria to reactive oxygen species generation while decreasing glutathione. Nitric oxide synthesis and hepatic iron are also elevated. Furthermore, activation of phagocytic NADPH oxidase 2 (Nox2) of host immune cells is likely to exacerbate oxidative stress in HCV-infected patients. Key mechanisms of HCC include: genome instability, epigenetic regulation, inflammation with chronic tissue injury and sustained cell proliferation, and modulation of cell growth and death. Oxidative stress, or Nox proteins, plays various roles in these mechanisms. Nox proteins also function in hepatic fibrosis, which commonly precedes HCC, and Nox4 elevation by HCV was mediated by transforming growth factor beta. This review summarizes mechanisms of oncogenesis by HCV, highlighting the role of oxidative stress and hepatic Nox enzymes in HCC. |
| Databáze: | OpenAIRE |
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