Geranylgeranylacetone promotes induction and secretion of thioredoxin in gastric mucosal cells and peripheral blood lymphocytes

Thioredoxin (TRX) is a redox-active protein which is induced by oxidative s tresses and shows a variety of biological activities including cytoprotecti on against oxidative stress. We recently reported that geranylgeranylaceton e (GGA), an and-ulcer drug, induces TRX in rat hepatocytes. In this study, we demonstrate that GGA promotes induction and secretion of TRX in rat gast ric mucosal cells and human peripheral blood lymphocytes (PBLs). Western bl otting and a sensitive sandwich ELISA showed that TRX was induced by GGA in the cell lysates and culture supernatants of rat gastric mucosal RGM-1 cel ls and human PBLs. LDH releasing assay showed that GGA protected rat gastri c mucosal RGM-1 cells from ethanol-induced cytotoxicity. Moreover, exogenou s recombinant wild type TRX decreased Cr-51 release from primary cultured r at gastric mucosal cells incubated with ethanol or hydrogen peroxide in a d ose-dependent manner, whereas recombinant mutant TRX (C32S/C35S), in which the two cysteines were replaced with serines in its active site, did not. T hese results indicate that GGA promotes the induction and secretion of TRX in a variety of types of cells and suggest that induced or secreted TRX may play an important role in the cytoprotective action of GGA on gastric muco sal cells.