Cruciferous vegetable phytochemical sulforaphane affects phase II enzyme expression and activity in rat cardiomyocytes through modulation of Akt signalling pathway.

The isothiocyanate sulforaphane (SF) is known to induce antioxidant/detoxification enzymes in many cancer cell lines, but studies focused on its cytoprotective action in non transformed cells are just at the beginning. Since we previously demonstrated that SF elicits cardioprotection through an indirect antioxidative mechanism, the aim of this study was to analyse the signalling pathways through which SF exerts its protective effects. Using cultured rat cardiomyocytes, we investigated the ability of SF to activate Akt/protein kinase B (PKB) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signalling pathways which are implicated in cardiac cell survival, and to increase the binding of nuclear factor E2-related factor 2 (Nrf2) to the antioxidant response element. By means of specific inhibitors, we demonstrated that the Phosphatidylinositol 3-kinas (PI3K)/Akt pathway represents a mechanism through which SF influences both expression and activity of glutathione reductase (GR), glutathione-S-transferase (GST), thioredoxin reductase (TR) and NAD(P)H:quinone oxidoreductase-1 (NQO1), analyzed by western immunoblotting and spectrophotometric assay respectively, and modulates Nrf2 binding resulting in a cytoprotective action against oxidative damage. Results of this study confirm the importance of phase II enzymes modulation as cytoprotective mechanism and support the use of chemical inducer SF as nutraceutical cardioprotective agent.