Resveratrol, a polyphenol derived e.g. from red grapes, has been shown to mediate several positive biological actions such as protection of cells against oxidative stress. It can also influence cell signaling, but the mechanisms behind its antioxidant properties are largely unknown. Here we show that RSV reduces oxidative stress and enhances cell survival in PC6.3 cells depending on the concentration. In these cells, RSV increased the levels of antioxidants, SOD2 and TRX2, and of X chromosome-linked inhibitor of apoptosis protein. RSV also activated NF kappa B signaling as shown using luciferase reporter constructs. These findings show that RSV regulates oxidative stress and mitochondrial antioxidants in neuronal cells. This may contribute to cell protection in various brain disorders. (C) 2010 Elsevier Ireland Ltd. All rights reserved.