Additive effect of ethanol and HCV subgenomic replicon expression on COX-2 protein levels and activity. 2007

K Trujillo-Murillo, and O Alvarez-Martínez, and L Garza-Rodríguez, and H Martínez-Rodríguez, and F Bosques-Padilla, and J Ramos-Jiménez, and H Barrera-Saldaña, and A R Rincón-Sánchez, and A M Rivas-Estilla
Department of Biochemistry, School of Medicine, UANL, Monterrey, Nuevo León, México.

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008156 Luciferases Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates. Luciferase
D012093 Replicon Any DNA sequence capable of independent replication or a molecule that possesses a REPLICATION ORIGIN and which is therefore potentially capable of being replicated in a suitable cell. (Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Replication Unit,Replication Units,Replicons,Unit, Replication,Units, Replication
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006526 Hepatitis C INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown. Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted,Parenterally-Transmitted Non-A, Non-B Hepatitis,PT-NANBH,Parenterally Transmitted Non A, Non B Hepatitis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000431 Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in ALCOHOLIC BEVERAGES. Alcohol, Ethyl,Absolute Alcohol,Grain Alcohol,Alcohol, Absolute,Alcohol, Grain,Ethyl Alcohol
D014779 Virus Replication The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle. Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015232 Dinoprostone The most common and most biologically active of the mammalian prostaglandins. It exhibits most biological activities characteristic of prostaglandins and has been used extensively as an oxytocic agent. The compound also displays a protective effect on the intestinal mucosa. PGE2,PGE2alpha,Prostaglandin E2,Prostaglandin E2alpha,PGE2 alpha,Prepidil Gel,Prostaglandin E2 alpha,Prostenon,E2 alpha, Prostaglandin,E2, Prostaglandin,E2alpha, Prostaglandin,Gel, Prepidil,alpha, PGE2,alpha, Prostaglandin E2
D016174 Hepacivirus A genus of FLAVIVIRIDAE causing parenterally-transmitted HEPATITIS C which is associated with transfusions and drug abuse. Hepatitis C virus is the type species. Hepatitis C virus,Hepatitis C-Like Viruses,Hepaciviruses,Hepatitis C Like Viruses,Hepatitis C viruses,Hepatitis C-Like Virus

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