Processing of peptides for antigen presentation is catalyzed by antigen-trimming enzymes, including the proteasome and leucine aminopeptidase. Oxidative stress suppresses proteasome function. We hypothesized that in liver cells, processing of antigenic peptides is altered by ethanol metabolism. To address this issue, soluble extracts of ethanol-metabolizing VL-17A cells treated with 100 mM ethanol or left untreated were incubated with C-extended or N-extended 18-27 HBV core peptides. T he proteasome is a multicatalytic enzyme crucially important for proteolysis of oxidized and misfolded proteins, peptides and short-lived signal transduction factors. In vivo, the proteasome exists in equilibrium as 2 particles: the 20S proteasome degrades substrate proteins with no prior ubiquitylation and the 26S form degrades ubiquitylated proteins in an ATP-dependent manner.Both 20S and 26S proteasomes generate peptides for MHC class I-restricted antigen presentation. 1,2 Processing of antigens is a necessary step for recognition by cytotoxic T lymphocytes (CTLs) of virally infected cells. To be recognized by CTLs, "nonself" antigens are processed to peptides of 8-10 amino acids, which then bind to MHC class I molecules in the endoplasmic reticulum. 3 Initial processing of antigenic proteins in the cytoplasm is catalyzed by the proteasome and/or leucine aminopeptidase (LAP). 4 Both enzymes are activated by the proinflammatory cytokine interferon gamma (IFN␥), 5 which induces formation of the immunoproteasome that cleaves antigenic proteins to uniformly sized peptides for presentation.The foregoing series of events occurs after hepatitis B or C infections during which CTLs eliminate HBV-infected or HCV-infected hepatocytes are based on ability of immune system to clear infected hepatocytes. Epidemiological studies have provided supporting evidence of

Background and Aims-The proteasome is a major cellular proteinase. Its activity is modulated by cellular oxidants. Hepatitis C core protein and ethanol exposure both cause enhanced oxidant generation. The aim was to investigate whether core protein, by its ability to generate oxidants, alters proteasome activity and whether these alterations are further affected byethanol exposure.

L-Buthionine (S,R) sulfoximine, administered with ethanol, significantly depleted hepatic glutathione, compared with controls. However, despite the decrease in hepatic antioxidant levels, liver injury by ethanol was alleviated, due, in part, to a BSO-elicited acceleration of ethanol metabolism.