1. Additive effect of ethanol and HCV subgenomic replicon expression on COX-2 protein levels and activity
- Author
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Ana Rosa Rincón-Sánchez, Ana María Rivas-Estilla, L. Garza-Rodríguez, Karina del Carmen Trujillo-Murillo, Javier Ramos-Jimenez, Francisco Bosques-Padilla, Herminia G. Martínez-Rodríguez, O. Álvarez-Martínez, and Hugo A. Barrera-Saldaña
- Subjects
Hepatitis C virus ,Hepacivirus ,Viral Nonstructural Proteins ,Virus Replication ,medicine.disease_cause ,Dinoprostone ,Cell Line ,chemistry.chemical_compound ,Virology ,medicine ,Humans ,Replicon ,Luciferases ,NS5A ,Ethanol ,Hepatology ,Oxidative Stress Pathway ,virus diseases ,Hepatitis C ,medicine.disease ,Molecular biology ,digestive system diseases ,Infectious Diseases ,Liver ,chemistry ,Viral replication ,Cyclooxygenase 2 ,Cell culture - Abstract
The mechanisms by which alcohol exacerbates liver injury in patients with hepatitis C are unknown. We used the hepatitis C virus (HCV) subgenomic replicon cell system to evaluate the effect of ethanol on HCV replication and viral protein synthesis. Our results demonstrate that alcohol stimulates HCV replicon expression at both HCV-RNA and protein levels. Furthermore, we observed that ethanol treatment showed an additive effect in cyclooxygenase-2 (COX-2) protein expression and activity already induced by HCV viral proteins, and in turn increased HCV viral expression. Our results suggest that COX-2 activity is involved in ethanol-induced HCV-RNA and NS5A protein expression, because acetylsalicylic acid (ASA), a COX-1/2 inhibitor, blocked this induction and downregulated COX-2 protein expression and activity. Therefore, we suggest that ethanol increases HCV replication expression, at least in part, by upregulating a key cellular regulator of oxidative stress pathway known as COX-2 or its products.
- Published
- 2007
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