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 stresses and shows a variety of biological activities including cytoprotection against oxidative stress. We recently reported that geranylgeranylacetone (GGA), an anti-ulcer drug, induces TRX in rat hepatocytes. In this study, we demonstrate that GGA promotes induction and secretion of TRX in rat gastric mucosal cells and human peripheral blood lymphocytes (PBLs). Western blotting 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 cells and human PBLs. LDH releasing assay showed that GGA protected rat gastric mucosal RGM-1 cells from ethanol-induced cytotoxicity. Moreover, exogenous recombinant wild type TRX decreased ⁵¹Cr release from primary cultured rat gastric mucosal cells incubated with ethanol or hydrogen peroxide in a dose-dependent manner, whereas recombinant mutant TRX (C32S/C35S), in which the two cysteines were replaced with serines in its active site, did not. These 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 mucosal cells.