title: Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells.
abstract: We evaluated the participation of oxidative stress in the negative regulation of hepatitis C virus (HCV)-RNA induced by acetylsalicylic acid (ASA). We used the HCV subgenomic replicon cell system that stably expresses HCV-nonstructural proteins (Huh7 HCV replicon cells) and the parental cell line. Cells were exposed to 4 mM ASA at different times (12-72 h), and pyrrolidine dithiocarbamate (PDTC) was used as an antioxidant control. Reactive oxygen species (ROS) production, oxidized protein levels, cytosolic superoxide dismutase (Cu/Zn-SOD), and glutathione peroxidase (GPx) activity were measured to evaluate oxidative stress. In addition, viral RNA and prostaglandin (PGE(2)) levels were determined. We observed that ASA treatment decreased ROS production and oxidized protein levels in a time-dependent fashion in both parental and HCV replicon cells with a greater extent in the latter. Similar results were found with PDTC exposure. Average GPx activity was decreased, whereas a striking increase was observed in average cytosolic SOD activity at 48 and 72 h in both cells exposed to ASA, compared with untreated cells. HCV replicon cells showed higher levels of Cu/Zn-SOD expression (mRNA and protein) with ASA treatment (48 and 72 h), whereas NS5A protein levels showed decreased expression. In addition, we found that inhibition of SOD1 expression reversed the effect of ASA. Interestingly, PDTC downregulated HCV-RNA expression (55%) and PGE(2) (60%) levels, imitating ASA exposure. These results suggest that ASA treatment could reduce cellular oxidative stress markers and modify Cu/Zn-SOD expression, a phenomenon that may contribute to the mechanisms involved in HCV downregulation.
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine, Autonomous University of Nuevo León, México. amrivas1@yahoo.ca
authors.forename: Ana María
authors.initials: AM
authors.lastname: Rivas-Estilla
authors.forename: Owen Lloyd
authors.initials: OL
authors.lastname: Bryan-Marrugo
authors.forename: Karina
authors.initials: K
authors.lastname: Trujillo-Murillo
authors.forename: Diana
authors.initials: D
authors.lastname: Pérez-Ibave
authors.forename: Claudia
authors.initials: C
authors.lastname: Charles-Niño
authors.forename: Cesar
authors.initials: C
authors.lastname: Pedroza-Roldan
authors.forename: Clara
authors.initials: C
authors.lastname: Ríos-Ibarra
authors.forename: Eda
authors.initials: E
authors.lastname: Ramírez-Valles
authors.forename: Rocío
authors.initials: R
authors.lastname: Ortiz-López
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Islas-Carbajal
authors.forename: Natalia
authors.initials: N
authors.lastname: Nieto
authors.forename: Ana Rosa
authors.initials: AR
authors.lastname: Rincón-Sánchez
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000975:Antioxidants; D000998:Antiviral Agents; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D001241:Aspirin