Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes.

Abstract

We have investigated the effect of transforming growth factor-beta 1 (TGF-beta 1) and three cytokines on expression of antioxidative enzymes, manganese-superoxide dismutase, copper, zinc-superoxide dismutase, and catalase in cultured hepatocytes of rat. While interleukin-1 beta and interleukin-6 induced manganese-superoxide dismutase gene expression, they slightly suppressed catalase gene expression in rat hepatocytes. TGF-beta 1 suppressed expression of all these antioxidative enzymes in time- and cell density-dependent manners. Furthermore, we examined the effect of TGF-beta 1 on expression of glutathione peroxidase and glutathione-S-transferase, which exhibit glutathione-dependent peroxidase activity in rat hepatocytes. Expression of two major classes of the rat glutathione-S-transferase subunits 1 and 2 was also reduced by TGF-beta 1, although expression of glutathione peroxidase was not affected. Flow cytometric analysis indicated that production of peroxides was increased in hepatocytes treated with TGF-beta 1. These data suggest that augmented production of hydrogen peroxide and its intermediate through suppression of antioxidative enzyme expression may participate in cellular injury or growth inhibition promoted by TGF-beta 1.