Inhibition of hepatitis C virus replication through adenosine monophosphate-activated protein kinase-dependent and -independent pathways |
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Authors: | Nakashima Kenji Takeuchi Kenji Chihara Kazuyasu Hotta Hak Sada Kiyonao |
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Affiliation: | Division of Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan. |
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Abstract: | Persistent infection with hepatitis C virus (HCV) is closely correlated with type 2 diabetes. In this study, replication of HCV at different glucose concentrations was investigated by using J6/JFH1-derived cell-adapted HCV in Huh-7.5 cells and the mechanism of regulation of HCV replication by AMP-activated protein kinase (AMPK) as an energy sensor of the cell analyzed. Reducing the glucose concentration in the cell culture medium from 4.5 to 1.0 g/L resulted in suppression of HCV replication, along with activation of AMPK. Whereas treatment of cells with AMPK activator 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) suppressed HCV replication, compound C, a specific AMPK inhibitor, prevented AICAR's effect, suggesting that AICAR suppresses the replication of HCV by activating AMPK in Huh-7.5 cells. In contrast, compound C induced further suppression of HCV replication when the cells were cultured in low glucose concentrations or with metformin. These results suggest that low glucose concentrations and metformin have anti-HCV effects independently of AMPK activation. |
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Keywords: | 5‐aminoimidazole‐4‐carboxamide 1‐β‐D‐ribofuranoside (AICAR) adenosine monophosphate‐activated protein kinase (AMPK) diabetes metformin |
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